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26,994 results on '"Epidemiology Unit"'

1. Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation.

Author: UK Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Cancer Research UK Programme, Wellcome Trust and the Royal Society, Dutch Heart Foundation, Dutch Federation of University Medical Centres, Netherlands Organisation for Health Research and Development, Royal Netherlands Academy of Sciences, Economic and Social Research Council (grant no. ES/N000404/1), Austrian Academy of Sciences, Min, Josine L., Hemani, Gibran, Hannon, Eilis, Dekkers, Koen F., Castillo-Fernandez, Juan, Luijk, René, Carnero-Montoro, Elena, Lawson, Daniel J., Burrows, Kimberley, Suderman, Matthew, Bretherick, Andrew D., Richardson, Tom G., Klughammer, Johanna, Iotchkova, Valentina, Sharp, Gemma, Al Khleifat, Ahmad, Shatunov, Aleksey, Iacoangeli, Aldredo, McArdle, Wendy L., Ho, Karen M., Kumar, Ashish, Söderhäll, C., Soriano-Tárraga, Carolina, Giralt-Steinhauer, Eva, Kazmi, Nabila, Mason, Dan, McRae, Allan F., Corcoran, David L., Sugden, Karen, Kasela, Silva, Cardona, Alexia, Day, Felix R., Cugliari, Giovanni, Viberti, Clara, Guarrera, Simonetta, Lerro, Michael, Gupta, Richa, Bollepalli, Sailalita, Mandaviya, Pooja, Zeng, Yanni, Clarke, Toni-Kim, Walker, Rosie M., Schmoll, V., Czamara, D., Ruiz-Arenas, Carlos, Rezwan, F. I., Marioni, R. E., Lin, T., Awaloff, Y., Barturen, G., Català-Moll, Frances, Kerick, Martin, Jiménez-Conde, Jordi, Roquer, Jaume, Gonzalez, Juan Ramón, Bustamante, Mariona, Sunyer, Jordi, Alarcón-Riquelme, Marta, UK Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Cancer Research UK Programme, Wellcome Trust and the Royal Society, Dutch Heart Foundation, Dutch Federation of University Medical Centres, Netherlands Organisation for Health Research and Development, Royal Netherlands Academy of Sciences, Economic and Social Research Council (grant no. ES/N000404/1), Austrian Academy of Sciences, Min, Josine L., Hemani, Gibran, Hannon, Eilis, Dekkers, Koen F., Castillo-Fernandez, Juan, Luijk, René, Carnero-Montoro, Elena, Lawson, Daniel J., Burrows, Kimberley, Suderman, Matthew, Bretherick, Andrew D., Richardson, Tom G., Klughammer, Johanna, Iotchkova, Valentina, Sharp, Gemma, Al Khleifat, Ahmad, Shatunov, Aleksey, Iacoangeli, Aldredo, McArdle, Wendy L., Ho, Karen M., Kumar, Ashish, Söderhäll, C., Soriano-Tárraga, Carolina, Giralt-Steinhauer, Eva, Kazmi, Nabila, Mason, Dan, McRae, Allan F., Corcoran, David L., Sugden, Karen, Kasela, Silva, Cardona, Alexia, Day, Felix R., Cugliari, Giovanni, Viberti, Clara, Guarrera, Simonetta, Lerro, Michael, Gupta, Richa, Bollepalli, Sailalita, Mandaviya, Pooja, Zeng, Yanni, Clarke, Toni-Kim, Walker, Rosie M., Schmoll, V., Czamara, D., Ruiz-Arenas, Carlos, Rezwan, F. I., Marioni, R. E., Lin, T., Awaloff, Y., Barturen, G., Català-Moll, Frances, Kerick, Martin, Jiménez-Conde, Jordi, Roquer, Jaume, Gonzalez, Juan Ramón, Bustamante, Mariona, Sunyer, Jordi, and Alarcón-Riquelme, Marta
Abstract: Characterizing genetic influences on DNA methylation (DNAm) provides an opportunity to understand mechanisms underpinning gene regulation and disease. In the present study, we describe results of DNAm quantitative trait locus (mQTL) analyses on 32,851 participants, identifying genetic variants associated with DNAm at 420,509 DNAm sites in blood. We present a database of >270,000 independent mQTLs, of which 8.5% comprise long-range (trans) associations. Identified mQTL associations explain 15–17% of the additive genetic variance of DNAm. We show that the genetic architecture of DNAm levels is highly polygenic. Using shared genetic control between distal DNAm sites, we constructed networks, identifying 405 discrete genomic communities enriched for genomic annotations and complex traits. Shared genetic variants are associated with both DNAm levels and complex diseases, but only in a minority of cases do these associations reflect causal relationships from DNAm to trait or vice versa, indicating a more complex genotype–phenotype map than previously anticipated.
Published: 2021

2. The efficacy of fungicides in the control of certain genera of plant-pathogenic fungi : a literature review

Author: Gould, Charles J., United States. Agricultural Research Service. Epidemiology Unit, U.S. Department of Agriculture, National Agricultural Library, Gould, Charles J., and United States. Agricultural Research Service. Epidemiology Unit
Subjects: Bibliography, Fungicides, Phytopathogenic fungi, United States
Published: 1954

3. Association of LPA Variants With Risk of Coronary Disease and the Implications for Lipoprotein(a)-Lowering Therapies

Author: Burgess, Stephen, Ference, Brian A., Staley, James R., Freitag, Daniel F., Mason, Amy M., Nielsen, Sune F., Willeit, Peter, Young, Robin, Surendran, Praveen, Karthikeyan, Savita, Bolton, Thomas R., Peters, James E., Kamstrup, Pia R., Tybjærg-Hansen, Anne, Benn, Marianne, Langsted, Anne, Schnohr, Peter, Vedel-Krogh, Signe, Kobylecki, Camilla J., Ford, Ian, Packard, Chris, Trompet, Stella, Jukema, J. Wouter, Sattar, Naveed, Di Angelantonio, Emanuele, Saleheen, Danish, Howson, Joanna M. M., Nordestgaard, Børge G., Butterworth, Adam S., Danesh, John, Medical Research Council Biostatistics Unit, University of Cambridge, Cambridge, United Kingdom, MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom, Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark, The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark, Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, Copenhagen, Denmark, Institute of Health and Wellbeing, University of Glasgow, Glasgow, United Kingdom, Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom, Department of Cardiology, Leiden University Medical Centre, Leiden, the Netherlands, and Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
Published: 2018

4. Mitochondrial polymorphisms and susceptibility to type 2 diabetes-related traits in Finns

Author: Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI, USA, Genome Technology Branch, National Human Genome Research Institute, Bethesda, MD, USA, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA, Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA, Diabetes and Genetic Epidemiology Unit, Department of Epidemiology and Health Promotion, and Department of Biochemistry, National Public Health Institute, Helsinki, Finland, Diabetes and Genetic Epidemiology Unit, Department of Epidemiology and Health Promotion, and Department of Biochemistry, National Public Health Institute, Helsinki, Finland, ; Department of Public Health, University of Helsinki, Helsinki, Finland, ; South Ostrobothnia Central Hospital, Sein??joki, Finland, Department of Genetics, University of North Carolina, 4109-F Neurosciences Research Building, 103 Mason Farm Road, CB#7264, 27599-7264, Chapel Hill, NC, USA, Ann Arbor, Chines, Peter S., Watanabe, Richard M., Boehnke, Michael, Buchanan, Thomas A., Conneely, Karen N., Narisu, Narisu, Erdos, Michael R., Valle, Timo T., Collins, Francis S., Enloe, Sareena, Bergman, Richard N., Tuomilehto, Jaakko, Mohlke, Karen L., Suh, Yong D., Peck, Erin C., Scott, Laura J., Jackson, Anne U., Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI, USA, Genome Technology Branch, National Human Genome Research Institute, Bethesda, MD, USA, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA, Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA, Diabetes and Genetic Epidemiology Unit, Department of Epidemiology and Health Promotion, and Department of Biochemistry, National Public Health Institute, Helsinki, Finland, Diabetes and Genetic Epidemiology Unit, Department of Epidemiology and Health Promotion, and Department of Biochemistry, National Public Health Institute, Helsinki, Finland, ; Department of Public Health, University of Helsinki, Helsinki, Finland, ; South Ostrobothnia Central Hospital, Sein??joki, Finland, Department of Genetics, University of North Carolina, 4109-F Neurosciences Research Building, 103 Mason Farm Road, CB#7264, 27599-7264, Chapel Hill, NC, USA, Ann Arbor, Chines, Peter S., Watanabe, Richard M., Boehnke, Michael, Buchanan, Thomas A., Conneely, Karen N., Narisu, Narisu, Erdos, Michael R., Valle, Timo T., Collins, Francis S., Enloe, Sareena, Bergman, Richard N., Tuomilehto, Jaakko, Mohlke, Karen L., Suh, Yong D., Peck, Erin C., Scott, Laura J., and Jackson, Anne U.
Abstract: Mitochondria play an integral role in ATP production in cells and are involved in glucose metabolism and insulin secretion, suggesting that variants in the mitochondrial genome may contribute to diabetes susceptibility. In a study of Finnish families ascertained for type 2 diabetes mellitus (T2DM), we genotyped single nucleotide polymorphisms (SNPs) based on phylogenetic networks. These SNPs defined eight major haplogroups and subdivided groups H and U, which are common in Finns. We evaluated association with both diabetes disease status and up to 14 diabetes-related traits for 762 cases, 402 non-diabetic controls, and 465 offspring of genotyped females. Haplogroup J showed a trend toward association with T2DM affected status (OR 1.69, P =0.056) that became slightly more significant after excluding cases with affected fathers (OR 1.77, P =0.045). We also genotyped non-haplogroup-tagging SNPs previously reported to show evidence for association with diabetes or related traits. Our data support previous evidence for association of T16189C with reduced ponderal index at birth and also show evidence for association with reduced birthweight but not with diabetes status. Given the multiple tests performed and the significance levels obtained, this study suggests that mitochondrial genome variants may play at most a modest role in glucose metabolism in the Finnish population. Furthermore, our data do not support a reported maternal inheritance pattern of T2DM but instead show a strong effect of recall bias.
Published: 2006

5. Variation in the resistin gene is associated with obesity and insulin-related phenotypes in Finnish subjects

Author: Department of Biostatistics, School of Public Health, University of Michigan, 1420 Washington Heights, Ann Arbor, MI 48109???2029, USA, Genome Technology Branch, National Human Genome Research Institute, Bethesda, Maryland, USA; Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland, Genome Technology Branch, National Human Genome Research Institute, Bethesda, Maryland, USA; Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA, Genome Technology Branch, National Human Genome Research Institute, Bethesda, Maryland, USA, Diabetes and Genetic Epidemiology Unit, Department of Epidemiology and Health Promotion, National Public Health Institute, Helsinki, Finland, Diabetes and Genetic Epidemiology Unit, Department of Epidemiology and Health Promotion, National Public Health Institute, Helsinki, Finland; Department of Public Health, University of Helsinki, Helsinki, Finland, Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California, USA, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA, Department of Medicine, Division of Endocrinology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA, Ann Arbor, Collins, Francis S., Bergman, Richard N., Watanabe, Richard M., Buchanan, Thomas A., Tuomilehto, Jaakko, Lazaridis, K.N., Scott, Laura J., Mohlke, Karen L., Silander, K., Boehnke, Michael, Conneely, Karen N., Valle, Timo T., Department of Biostatistics, School of Public Health, University of Michigan, 1420 Washington Heights, Ann Arbor, MI 48109???2029, USA, Genome Technology Branch, National Human Genome Research Institute, Bethesda, Maryland, USA; Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland, Genome Technology Branch, National Human Genome Research Institute, Bethesda, Maryland, USA; Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA, Genome Technology Branch, National Human Genome Research Institute, Bethesda, Maryland, USA, Diabetes and Genetic Epidemiology Unit, Department of Epidemiology and Health Promotion, National Public Health Institute, Helsinki, Finland, Diabetes and Genetic Epidemiology Unit, Department of Epidemiology and Health Promotion, National Public Health Institute, Helsinki, Finland; Department of Public Health, University of Helsinki, Helsinki, Finland, Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California, USA, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA, Department of Medicine, Division of Endocrinology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA, Ann Arbor, Collins, Francis S., Bergman, Richard N., Watanabe, Richard M., Buchanan, Thomas A., Tuomilehto, Jaakko, Lazaridis, K.N., Scott, Laura J., Mohlke, Karen L., Silander, K., Boehnke, Michael, Conneely, Karen N., and Valle, Timo T.
Abstract: Resistin is a peptide hormone produced by adipocytes that is present at high levels in sera of obese mice and may be involved in glucose homeostasis through regulation of insulin sensitivity. Several studies in humans have found associations between polymorphisms in the resistin gene and obesity, insulin sensitivity and blood pressure. An association between variation in the resistin gene and Type 2 diabetes has been reported in some, but not all studies. The aim of this study was to analyse variants of the resistin gene for association with Type 2 diabetes and related traits in a Finnish sample.
Published: 2006

6. Genome-wide linkage analysis of 1,233 prostate cancer pedigrees from the International Consortium for prostate cancer Genetics using novel sumLINK and sumLOD analyses

Author: University of Michigan ICPCG Group ; Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, University of Michigan ICPCG Group ; University of Michigan, Ann Arbor, Michigan, University of Utah ICPCG Group and Division of Genetic Epidemiology, University of Utah School of Medicine, Salt Lake City, Utah ; Division of Genetic Epidemiology, University of Utah School of Medicine, 391, Chipeta Way, Suite D, Salt Lake City, UT 84108., African American Hereditary Prostate Cancer ICPCG Group ; Fox Chase Cancer Center, Philadelphia, Pennsylvania ; National Human Genome Research Institute, NIH, Bethesda, Maryland, African American Hereditary Prostate Cancer ICPCG Group ; Fox Chase Cancer Center, Philadelphia, Pennsylvania, African American Hereditary Prostate Cancer ICPCG Group ; Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, African American Hereditary Prostate Cancer ICPCG Group ; National Human Genome Research Institute, NIH, Bethesda, Maryland, African American Hereditary Prostate Cancer ICPCG Group ; Translational Genomics Research Institute, Genetic Basis of Human Disease Research Division, Phoenix, Arizona, ACTANE Consortium ICPCG Group ; Cancer Epidemiology Centre, The Cancer Council Victoria, Melbourne, Australia, ACTANE Consortium ICPCG Group ; Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, The University of Melbourne, Melbourne, Australia, ACTANE Consortium ICPCG Group ; Department of Oncology, McGill University, Montreal, Quebec, Canada, ACTANE Consortium ICPCG Group ; The Norwegian Radium Hospital, Oslo, Norway, ACTANE Consortium ICPCG Group ; Institute of Cancer Research, Royal Marsden NHS Foundation Trust, Surrey, UK, ACTANE Consortium ICPCG Group ; Cancer Research UK Genetic Epidemiology Unit, Cambridge, UK, ACTANE Consortium ICPCG Group ; Division of Medical Genetics, University of Washington Medical Center, Seattle, Washington, BC/CA/HI ICPCG Group ; Department of Health Research and Policy, Stanford School of Medicine, Stanford, California ; Stanford Comprehensive Cancer Center, Stanford School of Medicine, Stanford, California, BC/CA/HI ICPCG Group ; Stanford Comprehensive Cancer Center, Stanford School of Medicine, Stanford, California, BC/CA/HI ICPCG Group ; Department of Urology and Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California, Data Coordinating Center for the ICPCG and Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, FHCRC ICPCG Group ; Fred Hutchinson Cancer Research Center, Divisions of Public Health Sciences, Seattle, Washington, FHCRC ICPCG Group ; Cancer Genetics Branch, National Institutes of Health, Bethesda, Maryland, FHCRC ICPCG Group ; Institute for Systems Biology, Seattle, Washington, Johns Hopkins University ICPCG Group and Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland, Mayo Clinic ICPCG Group and Mayo Clinic, Rochester, Minnesota, University of Tampere ICPCG Group, University of Tampere and Tampere University Hospital, Tampere, Finland, University of Ulm ICPCG Group ; Department of Urology, University of Ulm, Ulm, Germany, University of Ulm ICPCG Group ; Institute of Human Genetics, University of Ulm, Ulm, Germany, University of Ume?? ICPCG Group ; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, University of Ume?? ICPCG Group ; Oncologic Centre, Ume?? University, Ume??, Sweden, University of Utah ICPCG Group and Division of Genetic Epidemiology, University of Utah School of Medicine, Salt Lake City, Utah, Christensen, G. Bryce, Baffoe-Bonnie, Agnes B., George, Asha, Powell, Isaac, Bailey-Wilson, Joan E., Carpten, John D., Giles, Graham G., Hopper, John L., Severi, Gianluca, English, Dallas R., Foulkes, William D., Maehle, Lovise, Moller, Pal, Eeles, Ros, Easton, Douglas, Badzioch, Michael D., Whittemore, Alice S., Oakley-Girvan, Ingrid, Hsieh, Chih-Lin, Dimitrov, Latchezar, Xu, Jianfeng, Stanford, Janet L., Johanneson, Bo, Deutsch, Kerry, McIntosh, Laura, Ostrander, Elaine A., Wiley, Kathleen E., Isaacs, Sarah D., Walsh, Patrick C., Isaacs, William B., Thibodeau, Stephen N., McDonnell, Shannon K., Hebbring, Scott, Schaid, Daniel J., Lange, Ethan M., Cooney, Kathleen A., Tammela, Teuvo L. J., Schleutker, Johanna, Paiss, Thomas, Maier, Christiane, Gr??nberg, Henrik, Wiklund, Fredrik, Emanuelsson, Monica, Farnham, James M., Cannon-Albright, Lisa A., Camp, Nicola J., University of Michigan ICPCG Group ; Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, University of Michigan ICPCG Group ; University of Michigan, Ann Arbor, Michigan, University of Utah ICPCG Group and Division of Genetic Epidemiology, University of Utah School of Medicine, Salt Lake City, Utah ; Division of Genetic Epidemiology, University of Utah School of Medicine, 391, Chipeta Way, Suite D, Salt Lake City, UT 84108., African American Hereditary Prostate Cancer ICPCG Group ; Fox Chase Cancer Center, Philadelphia, Pennsylvania ; National Human Genome Research Institute, NIH, Bethesda, Maryland, African American Hereditary Prostate Cancer ICPCG Group ; Fox Chase Cancer Center, Philadelphia, Pennsylvania, African American Hereditary Prostate Cancer ICPCG Group ; Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, African American Hereditary Prostate Cancer ICPCG Group ; National Human Genome Research Institute, NIH, Bethesda, Maryland, African American Hereditary Prostate Cancer ICPCG Group ; Translational Genomics Research Institute, Genetic Basis of Human Disease Research Division, Phoenix, Arizona, ACTANE Consortium ICPCG Group ; Cancer Epidemiology Centre, The Cancer Council Victoria, Melbourne, Australia, ACTANE Consortium ICPCG Group ; Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, The University of Melbourne, Melbourne, Australia, ACTANE Consortium ICPCG Group ; Department of Oncology, McGill University, Montreal, Quebec, Canada, ACTANE Consortium ICPCG Group ; The Norwegian Radium Hospital, Oslo, Norway, ACTANE Consortium ICPCG Group ; Institute of Cancer Research, Royal Marsden NHS Foundation Trust, Surrey, UK, ACTANE Consortium ICPCG Group ; Cancer Research UK Genetic Epidemiology Unit, Cambridge, UK, ACTANE Consortium ICPCG Group ; Division of Medical Genetics, University of Washington Medical Center, Seattle, Washington, BC/CA/HI ICPCG Group ; Department of Health Research and Policy, Stanford School of Medicine, Stanford, California ; Stanford Comprehensive Cancer Center, Stanford School of Medicine, Stanford, California, BC/CA/HI ICPCG Group ; Stanford Comprehensive Cancer Center, Stanford School of Medicine, Stanford, California, BC/CA/HI ICPCG Group ; Department of Urology and Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California, Data Coordinating Center for the ICPCG and Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, FHCRC ICPCG Group ; Fred Hutchinson Cancer Research Center, Divisions of Public Health Sciences, Seattle, Washington, FHCRC ICPCG Group ; Cancer Genetics Branch, National Institutes of Health, Bethesda, Maryland, FHCRC ICPCG Group ; Institute for Systems Biology, Seattle, Washington, Johns Hopkins University ICPCG Group and Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland, Mayo Clinic ICPCG Group and Mayo Clinic, Rochester, Minnesota, University of Tampere ICPCG Group, University of Tampere and Tampere University Hospital, Tampere, Finland, University of Ulm ICPCG Group ; Department of Urology, University of Ulm, Ulm, Germany, University of Ulm ICPCG Group ; Institute of Human Genetics, University of Ulm, Ulm, Germany, University of Ume?? ICPCG Group ; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, University of Ume?? ICPCG Group ; Oncologic Centre, Ume?? University, Ume??, Sweden, University of Utah ICPCG Group and Division of Genetic Epidemiology, University of Utah School of Medicine, Salt Lake City, Utah, Christensen, G. Bryce, Baffoe-Bonnie, Agnes B., George, Asha, Powell, Isaac, Bailey-Wilson, Joan E., Carpten, John D., Giles, Graham G., Hopper, John L., Severi, Gianluca, English, Dallas R., Foulkes, William D., Maehle, Lovise, Moller, Pal, Eeles, Ros, Easton, Douglas, Badzioch, Michael D., Whittemore, Alice S., Oakley-Girvan, Ingrid, Hsieh, Chih-Lin, Dimitrov, Latchezar, Xu, Jianfeng, Stanford, Janet L., Johanneson, Bo, Deutsch, Kerry, McIntosh, Laura, Ostrander, Elaine A., Wiley, Kathleen E., Isaacs, Sarah D., Walsh, Patrick C., Isaacs, William B., Thibodeau, Stephen N., McDonnell, Shannon K., Hebbring, Scott, Schaid, Daniel J., Lange, Ethan M., Cooney, Kathleen A., Tammela, Teuvo L. J., Schleutker, Johanna, Paiss, Thomas, Maier, Christiane, Gr??nberg, Henrik, Wiklund, Fredrik, Emanuelsson, Monica, Farnham, James M., Cannon-Albright, Lisa A., and Camp, Nicola J.
Abstract: BACKGROUND Prostate cancer (PC) is generally believed to have a strong inherited component, but the search for susceptibility genes has been hindered by the effects of genetic heterogeneity. The recently developed sumLINK and sumLOD statistics are powerful tools for linkage analysis in the presence of heterogeneity. METHODS We performed a secondary analysis of 1,233 PC pedigrees from the International Consortium for Prostate Cancer Genetics (ICPCG) using two novel statistics, the sumLINK and sumLOD. For both statistics, dominant and recessive genetic models were considered. False discovery rate (FDR) analysis was conducted to assess the effects of multiple testing. RESULTS Our analysis identified significant linkage evidence at chromosome 22q12, confirming previous findings by the initial conventional analyses of the same ICPCG data. Twelve other regions were identified with genome-wide suggestive evidence for linkage. Seven regions (1q23, 5q11, 5q35, 6p21, 8q12, 11q13, 20p11???q11) are near loci previously identified in the initial ICPCG pooled data analysis or the subset of aggressive PC pedigrees. Three other regions (1p12, 8p23, 19q13) confirm loci reported by others, and two (2p24, 6q27) are novel susceptibility loci. FDR testing indicates that over 70% of these results are likely true positive findings. Statistical recombinant mapping narrowed regions to an average of 9???cM. CONCLUSIONS Our results represent genomic regions with the greatest consistency of positive linkage evidence across a very large collection of high-risk PC pedigrees using new statistical tests that deal powerfully with heterogeneity. These regions are excellent candidates for further study to identify PC predisposition genes. Prostate 70: 735???744, 2010. ?? 2010 Wiley-Liss, Inc.
Published: 2010

7. CHOLESTEROL LOWERING AND THE RISK OF CORONARY HEART DISEASE

Author: Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan 48109, U.S.A., Cardiovascular Epidemiology Unit, Nmewells Hospital and Medical School, Dundee DD19SY, United Kingdom, Department of Surgery, Medical School, University of Minnesota, Minneapolis, Minnesota 55455, U.S.A., Tunstall-Pedoe, Hugh, Buchwald, Henry, Matts, John P., Long, John M., Hawthorne, Victor M., Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan 48109, U.S.A., Cardiovascular Epidemiology Unit, Nmewells Hospital and Medical School, Dundee DD19SY, United Kingdom, Department of Surgery, Medical School, University of Minnesota, Minneapolis, Minnesota 55455, U.S.A., Tunstall-Pedoe, Hugh, Buchwald, Henry, Matts, John P., Long, John M., and Hawthorne, Victor M.
Published: 2006

8. Affected sibling pairs with juvenile idiopathic arthritis : An immunogenetic study of the disease in multicase families

Author: Helsingin yliopisto, lääketieteellinen tiedekunta, kliininen laitos, University of Helsinki, Faculty of Medicine, Institute of Clinical Medicine, Division of Rheumatology, Helsingfors universitet, medicinska fakulteten, institutionen för klinisk medicin, Rheumatism Foundation Hospital, Heinola; Diabetes and Genetic Epidemiology Unit, National Public Health Institute, Department of Public Health, University of Helsinki, Säilä, Hanna, Helsingin yliopisto, lääketieteellinen tiedekunta, kliininen laitos, University of Helsinki, Faculty of Medicine, Institute of Clinical Medicine, Division of Rheumatology, Helsingfors universitet, medicinska fakulteten, institutionen för klinisk medicin, Rheumatism Foundation Hospital, Heinola; Diabetes and Genetic Epidemiology Unit, National Public Health Institute, Department of Public Health, University of Helsinki, and Säilä, Hanna
Abstract: Genetic susceptibility to juvenile idiopathic arthritis (JIA) was studied in the genetically homogeneous Finnish population by collecting families with two or three patients affected by this disease from cases seen in the Rheumatism Foundation Hospital. The number of families ranged in different studies from 37 to 45 and the total number of patients with JIA, from among whom these cases were derived, was 2 000 to 2 300. Characteristics of the disease in affected siblings in Finland were compared with a population-based series and with a sibling series from the United States. A thorough clinical and ophthalmological examination was made of all affected patients belonging to sibpair series. Information on the occurrence of chronic rheumatic diseases in parents was collected by questionnaire and diagnoses were confirmed from hospital records. All patients, their parents and most of the healthy sibs were typed for human leukocyte antigen (HLA) alleles in loci A, C, B, DR and DQ. The HLA allele distribution of the cases was compared with corresponding data from Finnish bone marrow donors. The genetic component in JIA was found to be more significant than previously believed. A concordance rate of 25% for a disease with a population prevalence of 1 per 1000 implied a relative risk of 250 for a monozygotic (MZ) twin. An estimate for the sibling risk of an affected individual was about 15- to 20-fold. The disease was basically similar in familial and sporadic cases; the mean age at disease onset was however lower in familial cases, (4.8 years vs 7.4 years). Three sibpairs (3.4 expected) were concordant for the presence of asymptomatic uveitis. Uveitis would thus not appear to have any genetic component of its own, separate from the genetic basis of JIA. Four of the parents had JIA (0.2 cases expected), four had a type of rheumatoid factor-negative arthritis similar to that seen in juvenile patients but commencing in adulthood, and one had spondyloarthropathy (SPA). These fi, Lastenreuman perimmäiset syyt ovat yhä tuntemattomat. Se on monitekijäinen sairaus ja nykykäsityksen mukaan sen syntyyn vaikuttavat sekä perintö- että ympäristötekijät. Sekä geneettiset että ympäristötekijät vaikuttavat taudin ja sen alatyyppien esiintyvyyden eroihin eri väestöissä ja roduilla. Perintötekijöiden osuutta sairastavuuteen vahvistaa taudin suvuittainen kertyminen sekä kaksosaineistossa todettu konkordanssi. Lisäksi lastenreuman assosiotuminen tiettyihin kromosomi kuuden HLA-polymorfismeihin vahvistaa geneettisen komponentin osuutta. Perintötekijöiden etsinnässä lastenreumaa sairastavien potilaiden verinäytteistä määritellyistä markkereiden genotyyppitiedoista pyritään selvittämään mahdollista kytkeytymistä tautia aiheuttavaan geeniin. Aikaisemmissa tutkimuksissa vahvin lastenreumalle altistava geenialue näyttää koko genomin kattavan analyysin perusteella sijoittuvan HLA-alueelle, mutta muillakin genomin alueiden geeneillä on ilmeisesti vaikutusta. Suomalaisten geneettisiltä taustoiltaan homogeenisten potilaiden tutkiminen mahdollistaa monitekijäisten tautien, kuten lastenreuman tautikytkentöjen selvittämisen pienemmästäkin potilasmäärästä, koska 1) kytkentäepätasapainon uskotaan käsittävän suurempia kromosomipalasia ja 2) on todennäköistä, että suppeassa ns. perustajaväestössä on altistavia geenejä rajoitetusti. Tässä väitöskirjatutkimuksessa tutkittiin lastenreuman suvuittaista kertymistä ja HLA alleeli assosiaatioita kytkentä- ja assosiaatioanalyyseilla Reumasäätiön sairaalan sisaruspari-aineistossa.Väitöstutkimuksen tulokset osoittavat, että lastenreuman periytyvyys on selvästi voimakkaampaa kuin aikuisten nivelreumassa. Monotsygoottisten, perimältään identtisten kaksosten aineistossa todettiin, että 25%:ssa kumpikin kaksosparin jäsen sairasti lastenreumaa. Tätä verrattaessa lastenreuman esiintyvyyteen väestössä (1/1000) identtisen kaksosen riski sairastua, jos toisella on lastenreuma, on 250-kertainen. Muiden sisarusten sairastumisriski on arviolta
Published: 2006

9. Associations between exploratory dietary patterns and incident type 2 diabetes: a federated meta-analysis of individual participant data from 25 cohort studies

Author: Jannasch, Franziska, Dietrich, Stefan, Bishop, Tom RP, Pearce, Matthew, Fanidi, Anouar, O'Donoghue, Gráinne, O'Gorman, Donal, Marques-Vidal, Pedro, Vollenweider, Peter, Bes-Rastrollo, Maira, Byberg, Liisa, Wolk, Alicja, Hashemian, Maryam, Malekzadeh, Reza, Poustchi, Hossein, Luft, Vivian C, De Matos, Sheila M Alvim, Kim, Jihye, Kim, Mi Kyung, Kim, Yeonjung, Stern, Dalia, Lajous, Martin, Magliano, Dianna J, Shaw, Jonathan E, Akbaraly, Tasnime, Kivimaki, Mika, Maskarinec, Gertraud, Le Marchand, Loïc, Martínez-González, Miguel Ángel, Soedamah-Muthu, Sabita S, EPIC-InterAct Consortium, Wareham, Nicholas J, Forouhi, Nita G, Schulze, Matthias B, Medical and Clinical Psychology, Jannasch, Franziska [0000-0003-3478-4758], Apollo - University of Cambridge Repository, EPIC-InterAct Consortium, University of Cambridge [UK] (CAM), Université de Lausanne = University of Lausanne (UNIL), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, G03/140, PI10/02293, PI10/02658, PI13/00615, PI14/01668, PI14/01764, PI14/01798, PI17/01795, PI20/00564, PNSD-2020/021, LSHM_CT_2006_037197, 82DZD00302, 122/2014, 27/2011, 45/2011, PNSD 2020/2021, FKZ: 01EA1806A, National Institutes of Health, NIH: R01AG056477, RF1AG062553, U01 CA164973, National Cancer Institute, NCI, American Institute for Cancer Research, AICR: 05B047, GlaxoSmithKline, GSK, Centre International de Recherche sur le Cancer, CIRC, Wellcome Trust, WT: 221854/Z/20/Z, Horizon 2020 Framework Programme, H2020: 824989, Seventh Framework Programme, FP7: 602068, Manchester Biomedical Research Centre, BRC: IS-BRC-1215-20014, Medical Research Council, MRC: MC_UU_00006/1and MC_UU_00006/3, Cancer Research UK, CRUK: C20/A5860, National Research Foundation, NRF, Department of Science and Technology, Ministry of Science and Technology, India, डीएसटी, Deutsche Forschungsgemeinschaft, DFG: 491394008, NFDI 13/1, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, SNF: 33CS30-139468, 33CS30-148401, 33CS30_177535/1, 33CSCO-122661, MRCMR/R024227/1, Bundesministerium für Bildung und Forschung, BMBF, Consejo Nacional de Ciencia y Tecnología, CONACYT: S0008-2009-1: 000000000115312, Kementerian Sains, Teknologi dan Inovasi, MOSTI, Nederlandse Zuivel Organisatie, NZO, Conselho Nacional de Desenvolvimento Científico e Tecnológico, CNPq, Ministry of Science, ICT and Future Planning, MSIP: NRF-2017M3C9A6047623, Ministry of Health and Welfare, MOHW: 4845-301, 4851-302, Korea Centers for Disease Control and Prevention, KCDC, Seconda Università degli Studi di Napoli, SUN, Vetenskapsrådet, VR: 2017–00644, Universidad de Navarra, Tehran University of Medical Sciences and Health Services, TUMS: 81/15, Financiadora de Estudos e Projetos, FINEP: 01 06 0010.00, 01 06 0071.00, 01 06 0115.00, 01 06 0300.00, Ministério da Saúde, Mejeribrugets ForskningsFond, MFF, European Regional Development Fund, ERDF: RD 06/0045, Open Access funding enabled and organized by Projekt DEAL. The InterConnect project is funded by the European Union’s Seventh Framework Programme (grant number 602068). FJ and MBS acknowledge funding from the German Federal Ministry of Education and Research and the State of Brandenburg to the German Center for Diabetes Research (DZD) (82DZD00302). Furthermore, this work was supported by the NutriAct – Competence Cluster Nutrition Research Berlin-Potsdam funded by the German Federal Ministry of Education and Research (FKZ: 01EA1806A). This work was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - 491394008. This work was done as part of the NFDI4Health Consortium ( www.nfdi4health.de ). We gratefully acknowledge the financial support of the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – NFDI 13/1. NJW and NGF acknowledge funding from the Medical Research Council Epidemiology Unit (MC_UU_00006/1and MC_UU_00006/3) and NIHR Biomedical Research Centre Cambridge: Nutrition, Diet, and Lifestyle Research Theme (IS-BRC-1215-20014). NGF is an NIHR Senior Investigator (G111539). TB acknowledges funding from EUCAN-Connect under the European Union’s Horizon 2020 research and innovation programme (grant agreement number 824989). The InterAct project was funded by the EU FP6 programme (grant number LSHM_CT_2006_037197). MBR and MAMG acknowledge that the SUN Project has received funding from the Spanish Government-Instituto de Salud Carlos III, and the European Regional Development Fund (FEDER) (RD 06/0045, CIBER-OBN, Grants PI10/02658, PI10/02293, PI13/00615, PI14/01668, PI14/01798, PI14/01764, PI17/01795, PI20/00564 and G03/140), PNSD-2020/021, the Navarra Regional Government (27/2011, 45/2011, 122/2014), PNSD 2020/2021, and the University of Navarra. LB and AW acknowledge that the COSM and SMC are part of the Swedish Infrastructure for Medical Population-Based Life-Course and Environmental Research, SIMPLER. SIMPLER receives funding through the Swedish Research Council (grant no 2017–00644). RM acknowledges funding from the Tehran University of Medical Sciences (grant number: 81/15), Cancer Research UK (grant number: C20/A5860), the Intramural Research Program of the U.S. National Cancer Institute, NIH, and the International Agency for Research on Cancer. SMAM and VCL acknowledge that ELSA-Brasil was supported by the Brazilian Ministry of Health (Department of Science and Technology) and Ministry of Science, Technology and Innovation (Financiadora de Estudos e Projetos (FINEP), grant numbers 01 06 0010.00, 01 06 0212.00, 01 06 0300.00, 01 06 0278.00, 01 06 0115.00 and 01 06 0071.00) and the National Council for Scientific and Technological Development (CNPq). JK acknowledges funding from the Korea Centers for Disease Control and Prevention, Ministry for Health and Welfare, Republic of Korea (4845-301 and 4851-302), and the Collaborative Genome Program for Fostering New Post-Genome Industry of the National Research Foundation (NRF) funded by the Ministry of Science and ICT (NRF-2017M3C9A6047623). DS and ML acknowledge that this work of MTC was supported by the American Institute for Cancer Research (grant number 05B047) and the Consejo Nacional de Ciencia y Tecnología (CONACyT) (grant number S0008-2009-1: 000000000115312). LLM acknowledges funding from the US National Institutes of Health grant U01 CA164973, SSSM received the Wiebe Visser International Dairy Nutrition Prize and has received recent research funding (2019) for epidemiological studies on dairy products and cardiometabolic diseases from the Dutch Dairy Association and the Danish Dairy Research Foundation. PMV and PV acknowledge funding from GlaxoSmithKline, the Faculty of Biology and Medicine of Lausanne, and the Swiss National Science Foundation (grants 33CSCO-122661, 33CS30-139468, 33CS30-148401 and 33CS30_177535/1). MK and the Whitehall II study were supported by the UK Medical Research Council (MRCMR/R024227/1), the Wellcome Trust (221854/Z/20/Z) and the US National Institutes of Health (NIH, RF1AG062553, R01AG056477), during the conduct of the study. The funding sources did not participate in the design or conduct of the study, collection, management, analysis, or interpretation of the data, or preparation, review, or approval of the manuscript., We would like to thank the participants, principal investigators, and study teams of the individual cohorts included in this collaboration. The work presented herein was made possible using the OBiBa suite (http://www.obiba.org), a software suite developed by Maelstrom Research (www.maelstrom-research.org), and DataSHIELD (http://www.datashield.ac.uk), a software suite developed by the Data to Knowledge (D2K) Research Group. We thank EPIC-InterAct collaborators and Nicola Kerrison at the MRC Epidemiology Unit for assistance relating to the EPIC-InterAct dataset. We also thank the AusDiab Steering Committee for providing data from the AusDiab study. Moreover, we thank the NIH Biologic Specimen and Data Repository Information Coordinating Center and the ARIC, CARDIA, MESA, PRHHP and WHI OS study for providing data for this study., and HAL UVSQ, Équipe
Subjects: endocrine system diseases, Federated meta-analysis, Medicine (miscellaneous), BLOOD-PRESSURE, Endocrinology and Diabetes, PROFILE, Cohort Studies, Type 2 diabetes mellitus, Exploratory, Dietary patterns, DESIGN, Risk Factors, Humans, Prospective Studies, POPULATION, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, RISK, Diabetes Mellitus, Type 2/epidemiology, Diabetes Mellitus, Type 2/etiology, Diet, Incidence, Nutrition and Dietetics, OBJECTIVES, nutritional and metabolic diseases, CONSUMPTION, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Näringslära, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Diabetes Mellitus, Type 2, ATHEROSCLEROSIS, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Endokrinologi och diabetes, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, LIFE-STYLE, HEALTH, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: Funder: Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke (DIfE) (3440), PURPOSE: In several studies, exploratory dietary patterns (DP), derived by principal component analysis, were inversely or positively associated with incident type 2 diabetes (T2D). However, findings remained study-specific, inconsistent and rarely replicated. This study aimed to investigate the associations between DPs and T2D in multiple cohorts across the world. METHODS: This federated meta-analysis of individual participant data was based on 25 prospective cohort studies from 5 continents including a total of 390,664 participants with a follow-up for T2D (3.8-25.0 years). After data harmonization across cohorts we evaluated 15 previously identified T2D-related DPs for association with incident T2D estimating pooled incidence rate ratios (IRR) and confidence intervals (CI) by Piecewise Poisson regression and random-effects meta-analysis. RESULTS: 29,386 participants developed T2D during follow-up. Five DPs, characterized by higher intake of red meat, processed meat, French fries and refined grains, were associated with higher incidence of T2D. The strongest association was observed for a DP comprising these food groups besides others (IRRpooled per 1 SD = 1.104, 95% CI 1.059-1.151). Although heterogeneity was present (I2 = 85%), IRR exceeded 1 in 18 of the 20 meta-analyzed studies. Original DPs associated with lower T2D risk were not confirmed. Instead, a healthy DP (HDP1) was associated with higher T2D risk (IRRpooled per 1 SD = 1.057, 95% CI 1.027-1.088). CONCLUSION: Our findings from various cohorts revealed positive associations for several DPs, characterized by higher intake of red meat, processed meat, French fries and refined grains, adding to the evidence-base that links DPs to higher T2D risk. However, no inverse DP-T2D associations were confirmed.
Published: 2022

10. Development and validation of a lifestyle-based model for colorectal cancer risk prediction: the LiFeCRC score

Author: Amanda J. Cross, Kristin Benjaminsen Borch, Anne Kirstine Eriksen, Elio Riboli, José María Huerta, H. Bas Bueno-de-Mesquita, Giovanna Masala, Núria Sala, Anne Tjønneland, Anika Hüsing, Rudolf Kaaks, Sara Grioni, Anne M. May, Fanny Artaud, Antonia Trichopoulou, Pilar Amiano, Eleni Peppa, Marc J. Gunter, Timothy J. Key, Aurelio Barricarte Gurrea, Jonna Berntsson, Anna Karakatsani, Mazda Jenab, Elisabete Weiderpass, Isabel Drake, Christina C. Dahm, Torkjel M. Sandanger, Bethany Van Guelpen, Robin Reichmann, María José Sánchez, Guri Skeie, Konstantinos K. Tsilidis, Gianluca Severi, Carlotta Sacerdote, Sjoerd G. Elias, José Ramón Quirós, Marie-Christine Boutron-Ruault, Salvatore Panico, Krasimira Aleksandrova, Rosario Tumino, Sophia Harlid, Elom K. Aglago, [Aleksandrova,K, Reichmann,R] Nutrition, Immunity and Metabolism Senior Scientist Group, Department of Nutrition and Gerontology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany. [Aleksandrova,K, Reichmann,R] Institute of Nutritional Science, University of Potsdam, Potsdam, Germany. [Aleksandrova,K] Department of Epidemiological Methods and Etiological Research, Leibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany. [Kaaks,R, Hüsing,A] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Jenab,M, Weiderpass,E, Aglago,EK, Gunter,MJ] International Agency for Research on Cancer, World Health Organization, Lyon, France. [Bueno-de-Mesquita,HB] National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. [Bueno-de-Mesquita,HB, Cross,AJ, Tsilidis,KK, Riboli,E] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Dahm,CC] Department of Public Health, Aarhus University, Aarhus, Denmark. [Eriksen,AK, Tjønneland,A] Danish Cancer Society Research Center, Copenhagen, Denmark. [Artaud,F, Boutron-Ruault,MC, Severi,G] CESP, Faculté de Medicine, Université Paris-Saclay, Villejuif, France. [Artaud,F, Severi,G] Institut Gustave Roussy, Villejuif, France. [Severi,G] Dipartimento di Statistica, Informatica e Applicazioni 'G. Parenti' (DISIA), University of Florence, Florence, Italy. [Trichopoulou,A, Karakatsani,A, Peppa,E] Hellenic Health Foundation, Athens, Greece. [Karakatsani,A] 2nd Pulmonary Medicine Department, School of Medicine, National and Kapodistrian University of Athens, 'ATTIKON' University Hospital, Haidari, Greece. [Panico,S] EPIC Centre of Naples, Dipartimento di Medicina Clinica e Chirurgia, University of Naples Federico II, Naples, Italy. [Masala,G] 1Cancer Risk Factors and Lifestyle Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network – ISPRO, Florence, Italy. [Grioni,S] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy. [Sacerdote,C] Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), Turin, Italy. [Tumino,R] Cancer Registry and Histopathology Department, Provincial Health Authority (ASP), Ragusa, Italy. [Elias,SG, May,AM] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands. [Borch,KB, Sandanger,TM, Skeie,G] Department of Community Medicine, Health Faculty, UiT-the Arctic university of Norway, Tromsø, Norway. [Sánchez,MJ] Escuela Andaluza de Salud Pública (EASP), Granada, Spain. [Sánchez,MJ] Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain. [Sánchez,MJ, Huerta,JM, Gurrea,AB, Amiano,P] Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Sánchez,MJ] Universidad de Granada, Granada, Spain. [Huerta,JM] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Sala,N] Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Translational Research Laboratory, Catalan Institute of Oncology (ICO), Barcelona, Spain. [Sala,N] Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain. [Gurrea,AB] Navarra Public Health Institute, Pamplona, Spain. [Gurrea,AB] Navarra Institute for Health Research (IdiSNA), Pamplona, Spain. [Quirós,JR] Public Health Directorate, Asturias, Spain. [Amiano,P] Ministry of Health of the Basque Government, Public Health Division of Gipuzkoa, Biodonostia Health Research Institute, Donostia-San Sebastian, Spain. [Berntsson,J] Department of Clinical Sciences, Division of Oncology and Pathology, Lund University, Lund, Sweden. [Drake,I] Department of Clinical Sciences in Malmö, Lund University, Lund, Sweden. [van Guelpen,B, Harlid,S] Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden. [van Guelpen,B] Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden. [Key,T] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. [Tsilidis,KK] Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece., This work was supported by the German Research Foundation (DFG) (grant AL 1784/3-1), which funded the research position of Dr. Aleksandrova for organizing study conduct and analysis. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (DKFZ) and Federal Ministry of Education and Research (BMBF) (Germany), Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), Health Research Fund (FIS), Instituto de salud Carlos III PI13/00061 to Granada, PI13/ 01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236), Navarra and Catalonia (Catalan Institute of Oncology – ICO-IDIBELL) (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), and Cancer Research UK (C864/A14136 to EPIC-Norfolk and C8221/A19170 to EPICOxford), Medical Research Council (MR/N003284/1 and MC-UU_12015/1 to EPIC-Norfolk and MR/M012190/1 to EPIC-Oxford) (United Kingdom). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Open Access funding enabled and organized by Projekt DEAL.
Subjects: Male, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Statistics as Topic::Probability::Risk::Risk Assessment [Medical Subject Headings], lcsh:Medicine, Cancer prevention, Cohort Studies, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Calibration [Medical Subject Headings], 0302 clinical medicine, Risk Factors, Neoplasias colorrectales, Medicine, 030212 general & internal medicine, Prospective Studies, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Nutritional Status [Medical Subject Headings], 10. No inequality, Prospective cohort study, 11 Medical and Health Sciences, Framingham Risk Score, Risk screening, Lifestyle behaviour, Risk prediction, Colorectal cancer, Public Health, Global Health, Social Medicine and Epidemiology, General Medicine, Middle Aged, 3. Good health, European Prospective Investigation into Cancer and Nutrition, 030220 oncology & carcinogenesis, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Prospective Studies [Medical Subject Headings], Female, Risk assessment, Colorectal Neoplasms, Research Article, Cohort study, Estils de vida, Waist, Lifestyles, Nutritional Status, Check Tags::Male [Medical Subject Headings], Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings], Estil de vida, Risk Assessment, Riesgo, Estilo de vida, 03 medical and health sciences, Càncer colorectal, General & Internal Medicine, Humans, Life Style, business.industry, lcsh:R, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Statistics as Topic::Probability::Risk [Medical Subject Headings], Technology and Food and Beverages::Food and Beverages::Food::Vegetables [Medical Subject Headings], Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [Medical Subject Headings], Psychiatry and Psychology::Behavior and Behavior Mechanisms::Psychology, Social::Life Style [Medical Subject Headings], Nomogram, Lifestyle, Diet, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Check Tags::Female [Medical Subject Headings], Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Musculoskeletal Physiological Phenomena::Musculoskeletal Physiological Processes::Movement::Motor Activity::Exercise [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], business, Prevención de Enfermedades, Demography
Abstract: Background: Nutrition and lifestyle have been long established as risk factors for colorectal cancer (CRC). Modifiable lifestyle behaviours bear potential to minimize long-term CRC risk; however, translation of lifestyle information into individualized CRC risk assessment has not been implemented. Lifestyle-based risk models may aid the identification of high-risk individuals, guide referral to screening and motivate behaviour change. We therefore developed and validated a lifestyle-based CRC risk prediction algorithm in an asymptomatic European population. Methods: The model was based on data from 255,482 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study aged 19 to 70 years who were free of cancer at study baseline (1992–2000) and were followed up to 31 September 2010. The model was validated in a sample comprising 74,403 participants selected among five EPIC centres. Over a median follow-up time of 15 years, there were 3645 and 981 colorectal cancer cases in the derivation and validation samples, respectively. Variable selection algorithms in Cox proportional hazard regression and random survival forest (RSF) were used to identify the best predictors among plausible predictor variables. Measures of discrimination and calibration were calculated in derivation and validation samples. To facilitate model communication, a nomogram and a web-based application were developed. Results: The final selection model included age, waist circumference, height, smoking, alcohol consumption, physical activity, vegetables, dairy products, processed meat, and sugar and confectionary. The risk score demonstrated good discrimination overall and in sex-specific models. Harrell’s C-index was 0.710 in the derivation cohort and 0.714 in the validation cohort. The model was well calibrated and showed strong agreement between predicted and observed risk. Random survival forest analysis suggested high model robustness. Beyond age, lifestyle data led to improved model performance overall (continuous net reclassification improvement = 0.307 (95% CI 0.264–0.352)), and especially for young individuals below 45 years (continuous net reclassification improvement = 0.364 (95% CI 0.084–0.575)). Conclusions: LiFeCRC score based on age and lifestyle data accurately identifies individuals at risk for incident colorectal cancer in European populations and could contribute to improved prevention through motivating lifestyle change at an individual level., German Research Foundation (DFG) AL 1784/3-1, European Commission European Commission Joint Research Centre, International Agency for Research on Cancer, Danish Cancer Society, Ligue Contre le Cancer (France), Institut Gustave Roussy (France), Mutuelle Generale de l'Education Nationale (France), Institut National de la Sante et de la Recherche Medicale (Inserm), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (DKFZ) (Germany), Federal Ministry of Education & Research (BMBF), Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro (AIRC), Consiglio Nazionale delle Ricerche (CNR), Netherlands Government, World Cancer Research Fund International (WCRF), Instituto de Salud Carlos III PI13/00061 PI13/01162, Junta de Andalucia, Regional Government of Asturias (Spain), Regional Government of Basque Country (Spain), Regional Government of Murcia (Spain) 6236, Regional Government of Navarra (Spain), Regional Government of Catalonia (Catalan Institute of Oncology -ICO-IDIBELL) (Spain), Swedish Cancer Society, Swedish Research Council, County Council of Skane (Sweden), County Council of Vasterbotten (Sweden), Cancer Research UK C864/A14136 C8221/A19170, UK Research & Innovation (UKRI) Medical Research Council UK (MRC) MR/N003284/1 MC-UU_12015/1 MR/M012190/1, Projekt DEAL
Published: 2021

11. DNA methylation changes associated with prenatal mercury exposure

Author: Lozano, Manuel, Yousefi, Paul, Broberg, Karin, Soler-Blasco, Raquel, Miyashita, Chihiro, Pesce, Giancarlo, Kim, Woo Jin, Rahman, Mohammad, Bakulski, Kelly, Haug, Line, Ikeda-Araki, Atsuko, Huel, Guy, Park, Jaehyun, Relton, Caroline, Vrijheid, Martine, Rifas-Shiman, Sheryl, Oken, Emily, Dou, John, Kishi, Reiko, Gutzkow, Kristine, Annesi-Maesano, Isabella, Won, Sungho, Hivert, Marie-France, Fallin, M. Daniele, Vafeiadi, Marina, Ballester, Ferran, Bustamante, Mariona, Llop, Sabrina, Universitat de València (UV), University of Bristol [Bristol], Karolinska Institutet [Stockholm], Lund University [Lund], Hokkaido Information University, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Kangwon National University, Harvard Medical School [Boston] (HMS), University of Michigan [Dearborn], University of Michigan System, Norwegian Institute of Public Health [Oslo] (NIPH), Seoul National University [Seoul] (SNU), Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Spanish Consortium for Research on Epidemiology and Public Health, CIBER de Epidemiología y Salud Pública (CIBERESP), Universitat Pompeu Fabra [Barcelona] (UPF), Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Johns Hopkins University (JHU), University of Crete [Heraklion] (UOC), 1999SGR 00241, 15/0025, 17/00260, 20/0006, FIS-FEDER PI16/1288, FIS-FEDER PI19/1338, FIS-FEDER-PI03–1615, FIS-FEDER-PI06/0867, FIS-PI04/1436, FIS-PI08/1151, FIS-PI11/00610, MC_UU_00011/5, National Institutes of Health, NIH: R37 HD034568, National Institute of Diabetes and Digestive and Kidney Diseases, NIDDK: R01 DK10324, National Institute of Neurological Disorders and Stroke, NINDS: 06A1, 1 UO1 NS 047537–01, National Institute of Environmental Health Sciences, NIEHS: N01-ES-75558, Z01-ES-49019, Centre International de Recherche sur le Cancer, CIRC, Japan Agency for Medical Research and Development, AMED: JPMH18950314, JPMH19188595, Wellcome Trust, WT: 102215/2/13/2, Horizon 2020 Framework Programme, H2020: 874583, Medical Research Council, MRC: MC_UU_12013_1, MC_UU_12013_2, MC_UU_12013_5, MC_UU_12013_8, WT088806, Biotechnology and Biological Sciences Research Council, BBSRC: BB/I025263/1, BB/I025751/1, European Commission, EC: 261357, European Research Council, ERC: 268479, University of Bristol, Japan Society for the Promotion of Science, KAKEN, Ministry of Education, Culture, Sports, Science and Technology, Monbusho: JP15H04780, JP16H02645, JP18H03035, JP18K10022, JP18K10042, JP19H01071, JP19K10576, JP19K10636, JP19K20457, JP19K22730, JPMEERF20145054, JPMEERF20175053, JPMEERF20205002, Bundesministerium für Bildung und Forschung, BMBF, Generalitat Valenciana, GVA: 090,430, BEST/2020/059, Ministry of Health, Labour and Welfare, MHLW: JPMH14427175, JPMH17932352, JPMH19189425, Helse- og Omsorgsdepartementet, Ministry of Environment, MOE: 2017001360005, Korea Environmental Industry and Technology Institute, KEITI, Instituto de Salud Carlos III, ISCIII: CB06/02/0041, INMA G03/176, Ministerio de Ciencia e Innovación, MICINN: MTM2015-68140-R, Seventh Framework Programme, FP7: R01HL111108, R01NR013945, Norges Forskningsråd: 221097, Institut National Du Cancer, INCa, Horizon 2020: 733206, Ministry of Internal Affairs and Communications, MIC: JPMI10001, Consejería de Educación e Investigación, The Norwegian Mother, Father and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research , NIH/NIEHS (contract no N01-ES-75558 ), NIH/NINDS (grant no. 1 UO1 NS 047537–01 and grant no.2 UO1 NS 047537–06A1 ). MoBa1 and MoBa 2 are supported by the Intramural Research Program of the NIH , National Institute of Environmental Health Sciences ( Z01-ES-49019 ) and Norwegian Research Council /BIOBANK (grant no 221097 ). The work in MoBa3 was supported in part by a Postdoctoral Fellowship grant from the Ulleval Hospitals Research Council (now under Oslo University Hospital) and travel grants from the Unger-Vetlesens foundation and the Norwegian American Womens Club , all to M.C.M.K. MoBa3 epigenomics data analyses were funded by INCA/Plan Cancer-EVA-INSERM, France, and the International Childhood Cancer Cohort Consortium (I4C), and performed by the Epigenetics Group at the International Agency for Research on Cancer (IARC, Lyon, France), A.G. was supported by the grant from INCA /Plan Cancer-EVA-INSERM (France, 2015) to Z.H. and also by the IARC Postdoctoral Fellowship, partially supported by the EC FP7 Marie Curie Actions-People-Co-funding of regional, national and international programmes (COFUND)., ALSPAC study was funded by the UK Medical Research Council and the Wellcome Trust (grant ref: 102215/2/13/2 ) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors, PY and CR, who will serve as guarantors for the contents of this paper. A comprehensive list of grants funding is available on the ALSPAC website ( http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf ). The Accessible Resource for Integrated Epigenomics Studies (ARIES), was funded by the UK Biotechnology and Biological Sciences Research Council ( BB/I025751/1 and BB/I025263/1 ). Additional epigenetic profiling of ALSPAC was supported by the UK Medical Research Council (MRC) Integrative Epidemiology Unit and the University of Bristol ( MC_UU_12013_1 , MC_UU_12013_2 , MC_UU_12013_5 and MC_UU_12013_8 ), the Wellcome Trust ( WT088806 ) and the United States National Institute of Diabetes and Digestive and Kidney Diseases ( R01 DK10324 ). PY and CR are supported by the UK MRC Integrative Epidemiology Unit ( MC_UU_00011/5 )., The Project Viva cohort is funded by NIH grants R01HL111108 , R01NR013945 , and R37 HD034568 ., The Hokkaido-Sapporo Study is supported by Grant-in-Aid for Scientific Research from the Japanese Ministry of Health , Labour and Welfare ( JPMH14427175 , JPMH19189425 , JPMH17932352 ), the Japan Society for the Promotion of Science, the Ministry of Education, Culture, Sports, Science and Technology ( JP16H02645 , JP19H01071 , JP18H03035 , JP15H04780 , JP19K10576 , JP19K10636 , JP18K10042 , JP18K10022 , JP19K22730 , JP19K20457 ), and an Environment Research and Technology Development fund ( JPMEERF20145054 , JPMEERF20175053 , JPMEERF20205002 ), AMED ( JPMH19188595 , JPMH18950314 ), and Ministry of Internal Affairs and Communications ( JPMI10001 )., Main funding of the epigenetic studies in INMA were grants from Instituto de Salud Carlos III ( Red INMA G03/176 , CB06/02/0041 ), Spanish Ministry of Health ( FIS-PI04/1436 , FIS-PI08/1151 including FEDER funds, FIS-PI11/00610 , FIS-FEDER-PI06/0867 , FIS-FEDER-PI03–1615 , FIS-FEDER PI16/1288 , FIS-FEDER PI19/1338, Miguel Servet FEDER 15/0025 and 20/0006, FIS-FSE : 17/00260 ), Generalitat de Catalunya-CIRIT 1999SGR 00241 , Generalitat Valenciana BEST/2020/059 , Fundacio ́ La Marato ́ de TV3 ( 090,430 ), EU Commission ( 261357 -MeDALL: Mechanisms of the Development of ALLergy), and European Research Council ( 268479 -BREATHE: Brain dEvelopment and Air polluTion ultrafine particles in school childrEn)., The authors would also like to thank Ingvild Essen for thorough field work, Heidi Marie Nordheim for biological sample management and the MoBa administrative unit (MoBa). The MoBa Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research . We are grateful to all the participating families in Norway who take part in this on-going cohort study., The Rhea project was financially supported by European projects , and the Greek Ministry of Health (Program of Prevention of Obesity and Neurodevelopmental Disorders in Preschool Children, in Heraklion district, Crete, Greece: 2011–2014, ‘Rhea Plus': Primary Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health: 2012–2015). The work was also supported by MICINN ( MTM2015-68140-R ), Centro Nacional de Genotipado - CEGEN-PRB2-ISCIII, the H2020 -EU.3.1.2. - Preventing Disease Programme (grant agreement no 874583 ) (ATHLETE project), and from the European Union's Horizon 2020 research and innovation programme (grant Agreement number: 733206 ) (Early Life stressors and Lifecycle Health (LIFECYCLE))., This study was supported by the Korean Environment Industry & Technology Institute ( KEITI ) through 'the Environmental Health Action Program', funded by Korea Ministry of Environment ( 2017001360005 )., ALSPAC. ALSPAC study is extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses. We would like to acknowledge Oliver Lyttleton, Hashem Shihab, Nabila Kazmi and Geoff Woodward for their earlier contribution to the generation of ARIES data (ALSPAC methylation data). INMA, The authors would like to thank all the participants for their generous collaboration. full roster of the INMA project investigators can be found at http://www.proyectoinma.org/presentacion-inma/listado-investigadores/en_listado-investigadores.html. MoBa, The authors would also like to thank Ingvild Essen for thorough field work, Heidi Marie Nordheim for biological sample management and the MoBa administrative unit (MoBa). The MoBa Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research. We are grateful to all the participating families in Norway who take part in this on-going cohort study. Project Viva, Project Viva researchers would like to thank all mothers, children and families for their ongoing participation. RHEA, The authors would like to thank Georgia Chalkiadaki and Danai Feida for biological sample management, to Eirini Michalaki, Mariza Kampouri, Anny Kyriklaki and Minas Iakovidis for field study performance and to Maria Fasoulaki for administrative assistance. SAPPORO-HOKKAIDO, We would like to express our appreciation to all of the study participants of the Hokkaido Study on Environment and Children? Health. We also express our profound gratitude to all personnel in the hospitals and clinics that collaborated with the study, including Sapporo Toho Hospital, Keiai Hospital, Endo Kikyo Maternity Clinic, Shiroishi Hospital, Memuro Municipal Hospital, Aoba Ladies Clinic, Obihiro-Kyokai Hospital, Akiyama Memorial Hospital, Sapporo Medical University Hospital, Hokkaido University Hospital, Kitami Red Cross Hospital, Hoyukai Sapporo Hospital, Gorinbashi Hospital, Hashimoto Clinic, Asahikawa Medical College Hospital, Hakodate Central General Hospital, Ohji General Hospital, Nakashibetsu Municipal Hospital, Sapporo Tokushukai Hospital, Asahikawa Red Cross Hospital, Wakkanai City Hospital, Kushiro Rosai Hospital, Sapporo-Kosei General Hospital, Shibetsu City General Hospital, Nikko Memorial Hospital, Sapporo City General Hospital, Kohnan Hospital, Hakodate City Hospital, Hokkaido Monbetsu Hospital, Tenshi Hospital, Hakodate Goryoukaku Hospital, Nakamura Hospital, Kin-ikyo Sapporo Hospital, Kitami Lady's Clinic, Engaru-Kosei General Hospital, Kushiro Red Cross Hospital, Nayoro City General Hospital, and Obihiro-Kosei General Hospital. We also deeply express our gratitude to the staff of The Hokkaido Study on Environment and Children's Health for their considerable efforts to support our study, including N. Goto, O. Hayashi, T. Hikichi, N. Kanda, K. Kunita, K. Miura, Y. Shibasaki, K. Sugawara, K. Tanaka, E. Toyama, and T. Yoshikawa. Special thanks to Ms. Mimi Takahashi on her effort to support writing this manuscript.ALSPAC study was funded by the UK Medical Research Council and the Wellcome Trust (grant ref: 102215/2/13/2) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors, PY and CR, who will serve as guarantors for the contents of this paper. A comprehensive list of grants funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). The Accessible Resource for Integrated Epigenomics Studies (ARIES), was funded by the UK Biotechnology and Biological Sciences Research Council (BB/I025751/1 and BB/I025263/1). Additional epigenetic profiling of ALSPAC was supported by the UK Medical Research Council (MRC) Integrative Epidemiology Unit and the University of Bristol (MC_UU_12013_1, MC_UU_12013_2, MC_UU_12013_5 and MC_UU_12013_8), the Wellcome Trust (WT088806) and the United States National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK10324). PY and CR are supported by the UK MRC Integrative Epidemiology Unit (MC_UU_00011/5).Main funding of the epigenetic studies in INMA were grants from Instituto de Salud Carlos III (Red INMA G03/176, CB06/02/0041), Spanish Ministry of Health (FIS-PI04/1436, FIS-PI08/1151 including FEDER funds, FIS-PI11/00610, FIS-FEDER-PI06/0867, FIS-FEDER-PI03?1615, FIS-FEDER PI16/1288, FIS-FEDER PI19/1338, FIS-FSE: 17/00260), Generalitat de Catalunya-CIRIT 1999SGR 00241, Generalitat Valenciana BEST/2020/059, Fundacio ? La Marato ? de TV3 (090,430), EU Commission (261357-MeDALL: Mechanisms of the Development of ALLergy), and European Research Council (268479-BREATHE: Brain dEvelopment and Air polluTion ultrafine particles in school childrEn).This study was supported by the Korean Environment Industry & Technology Institute (KEITI) through ?the Environmental Health Action Program?, funded by Korea Ministry of Environment (2017001360005).The Norwegian Mother, Father and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research, NIH/NIEHS (contract no N01-ES-75558), NIH/NINDS (grant no.1 UO1 NS 047537?01 and grant no.2 UO1 NS 047537?06A1). MoBa1 and MoBa 2 are supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES-49019) and Norwegian Research Council/BIOBANK (grant no 221097). The work in MoBa3 was supported in part by a Postdoctoral Fellowship grant from the Ulleval Hospitals Research Council (now under Oslo University Hospital) and travel grants from the Unger-Vetlesens foundation and the Norwegian American Womens Club, all to M.C.M.K. MoBa3 epigenomics data analyses were funded by INCA/Plan Cancer-EVA-INSERM, France, and the International Childhood Cancer Cohort Consortium (I4C), and performed by the Epigenetics Group at the International Agency for Research on Cancer (IARC, Lyon, France), A.G. was supported by the grant from INCA/Plan Cancer-EVA-INSERM (France, 2015) to Z.H. and also by the IARC Postdoctoral Fellowship, partially supported by the EC FP7 Marie Curie Actions-People-Co-funding of regional, national and international programmes (COFUND).The Project Viva cohort is funded by NIH grants R01HL111108, R01NR013945, and R37 HD034568.The Rhea project was financially supported by European projects, and the Greek Ministry of Health (Program of Prevention of Obesity and Neurodevelopmental Disorders in Preschool Children, in Heraklion district, Crete, Greece: 2011?2014, Rhea Plus': Primary Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health: 2012?2015). The work was also supported by MICINN (MTM2015-68140-R), Centro Nacional de Genotipado-CEGEN-PRB2-ISCIII, the H2020-EU.3.1.2. - Preventing Disease Programme (grant agreement no 874583) (ATHLETE project), and from the European Union's Horizon 2020 research and innovation programme (grant Agreement number: 733206) (Early Life stressors and Lifecycle Health (LIFECYCLE)).The Hokkaido-Sapporo Study is supported by Grant-in-Aid for Scientific Research from the Japanese Ministry of Health, Labour and Welfare (JPMH14427175, JPMH19189425, JPMH17932352), the Ministry of Education, Culture, Sports, Science and Technology (JP16H02645, JP19H01071, JP18H03035, JP15H04780, JP19K10576, JP19K10636, JP18K10042, JP18K10022, JP19K22730, JP19K20457), and an Environment Research and Technology Development fund (JPMEERF20145054, JPMEERF20175053, JPMEERF20205002), AMED (JPMH19188595, JPMH18950314), and Ministry of Internal Affairs and Communications (JPMI10001)., European Project: 261357,EC:FP7:HEALTH,FP7-HEALTH-2010-single-stage,MEDALL(2010), HAL UVSQ, Équipe, and Mechanisms of the Development of ALLergy - MEDALL - - EC:FP7:HEALTH2010-12-01 - 2015-05-31 - 261357 - VALID
Subjects: [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, [SDV.TOX] Life Sciences [q-bio]/Toxicology, DNA methylation, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Prenatal exposure, [SDV.TOX]Life Sciences [q-bio]/Toxicology, [SDV.EE.SANT] Life Sciences [q-bio]/Ecology, environment/Health, Methylmercury, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Mercury, ALSPAC, HELIX study, PACE
Abstract: International audience; Mercury (Hg) is a ubiquitous heavy metal that originates from both natural and anthropogenic sources and is transformed in the environment to its most toxicant form, methylmercury (MeHg). Recent studies suggest that MeHg exposure can alter epigenetic modifications during embryogenesis. In this study, we examined associations between prenatal MeHg exposure and levels of cord blood DNA methylation (DNAm) by meta-analysis in up to seven independent studies (n = 1462) as well as persistence of those relationships in blood from 7 to 8 year-old children (n = 794). In cord blood, we found limited evidence of differential DNAm at cg24184221 in MED31 (β = 2.28 × 10−4, p-value = 5.87 × 10−5) in relation to prenatal MeHg exposure. In child blood, we identified differential DNAm at cg15288800 (β = 0.004, p-value = 4.97 × 10−5), also located in MED31. This repeated link to MED31, a gene involved in lipid metabolism and RNA Polymerase II transcription function, may suggest a DNAm perturbation related to MeHg exposure that persists into early childhood. Further, we found evidence for association between prenatal MeHg exposure and child blood DNAm levels at two additional CpGs: cg12204245 (β = 0.002, p-value = 4.81 × 10−7) in GRK1 and cg02212000 (β = −0.001, p-value = 8.13 × 10−7) in GGH. Prenatal MeHg exposure was associated with DNAm modifications that may influence health outcomes, such as cognitive or anthropometric development, in different populations.
Published: 2022

12. Autoimmunity plays a role in the onset of diabetes after 40 years of age

Author: Vittorio Krogh, Rudolf Kaaks, Yvonne T. van der Schouw, Gianluca Severi, Eva Ardanaz, Marc J. Gunter, Tilman Kühn, Nicholas J. Wareham, Timothy J. Key, Francesca Mancini, Carlotta Sacerdote, María José Sánchez, Heiner Boeing, Annemieke M.W. Spijkerman, Peter M. Nilsson, Guy Fagherazzi, Miren Dorronsoro, María Dolores Chirlaque, Kay-Tee Khaw, Olov Rolandsson, Stephen J. Sharp, Salvatore Panico, Domenico Palli, Nita G. Forouhi, Christiane S. Hampe, Claudia Langenberg, Kim Overvad, Rosario Tumino, Elio Riboli, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), LSHM_CT_2006_037197 N∫ 6236 National Institutes of Health, NIH: DK26190 Compagnia di San Paolo Kræftens Bekæmpelse, DCS German Cancer Research Center, DKFZ Medical Research Council, MRC: MC_UU_12015/1, MC_UU_12015/5, MR/N003284/1 Cancer Research UK, CRUK World Cancer Research Fund, WCRF Bundesministerium für Bildung und Forschung, BMBF Västerbotten Läns Landsting Ministerie van Volksgezondheid, Welzijn en Sport, VWS Agentschap NL: IGE05012 Vetenskapsrådet, VR Umeå Universitet Bundesministerium für Forschung und Technologie, BMFT Deutsche Krebshilfe Bundesministerium fÃ¼r Bildung und Frauen, BMBF Stichting Diabetes Onderzoek Nederland NIHR Imperial Biomedical Research Centre, BRC NIHR Cambridge Biomedical Research Centre: IS-BRC-1215-20014, O. Rolandsson: The Västerboten County Council, M. Dorronsoro: We thank the participants of the Spanish EPIC cohort for their contribution to the study as well as to the team of trained nurses who participated in the recruitment, R. Kaaks: German Cancer Aid, German Ministry of Research (BMBF), K. T. Khaw: Medical Research Council UK, Cancer Research UK, T. Kühn: German Cancer Aid, German Cancer Research Center (DKFZ), German Federal Ministry of Education and Research (BMBF), S. Panico: Compagnia di San Paolo, A. M. W. Spijkerman: EPIC Bilthoven and Utrecht acknowledge the Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), Statistics Netherlands (the Netherlands), EPIC Ragusa acknowledges for their participation blood donors of AVIS-Ragusa (local blood donors association), Y. T. van der Schouw: EPIC Bilthoven and Utrecht acknowledge the Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), Dutch ZON (Zorg Onderzoek Nederland), WCRF, Statistics Netherland, E. Riboli: Imperial College Biomedical Research Centre., Open access funding provided by Umea University. Funding for the InterAct project was provided by the EU FP6 Programme (grant number LSHM_CT_2006_037197). The autoantibody measurement was funded by Västerbotten County Council and Umeå University, Sweden (OR), the National Institutes of Health (DK26190) (CSH) and the Medical Research Council (MC_UU_12015/1) (NJW). OR: the Västerbotten County Council, Umeå University, MDC: Health Research Fund (FIS) of the Spanish Ministry of Health, Murcia Regional Government (N∫ 6236), EA: the Health Research Fund (FIS) of the Spanish Ministry of Health and Navarre Regional Government, RK: German Cancer Aid, the German Ministry of Research (BMBF), TJK: Cancer Research UK, KTK: the Medical Research Council UK, Cancer Research UK, PMN: the Swedish Research Council, KO: the Danish Cancer Society, SP: Compagnia di San Paolo, AMWS: the Dutch Ministry of Public Health, Welfare and Sports (VWS), the Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands, RT: AIRE-ONLUS Ragusa, AVIS-Ragusa, Sicilian Regional Government, AMWS: LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), YTvdS: verification of diabetes cases was additionally funded by NL Agency grant IGE05012 and an Incentive Grant from the Board of the UMC Utrecht, LK Research Funds, Dutch Prevention Funds, NGF: MRC core support (MC_UU_12015/5), NIHR Cambridge Biomedical Research Centre (IS-BRC-1215-20014). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Acknowledgements, We thank all EPIC participants and staff for their contribution to this study. We thank N. Kerrison (MRC Epidemiology Unit, Cambridge, UK) for managing the data and the laboratory team at the MRC Epidemiology Unit, Cambridge for managing the blood samples for the EPIC-InterAct project. We thank the participants of the Spanish EPIC cohort for their contribution to the study as well as the team of trained nurses who participated in the recruitment. O. Rolandsson: The V?sterboten County Council, T. K?hn: German Cancer Aid, German Cancer Research Center (DKFZ), German Federal Ministry of Education and Research (BMBF), E. Riboli: Imperial College Biomedical Research Centre. Some of the data were presented as an abstract at the 54th EASD Annual Meeting in 2018., Rolandsson, Olov [0000-0002-1341-6828], and Apollo - University of Cambridge Repository
Subjects: Male, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Autoimmunity, Type 2 diabetes, medicine.disease_cause, LADA, Endocrinology, Autoantibody, 0302 clinical medicine, POPULATION, RISK, 0303 health sciences, Glutamate Decarboxylase, ANTIBODY POSITIVITY, GAD, Middle Aged, Phenotype, Genetic risk score, Pathophysiology, 3. Good health, Diabetes and Metabolism, Type 1 diabetes, Endokrinologi och diabetes, Female, Life Sciences & Biomedicine, Adult, 030209 endocrinology & metabolism, Endocrinology and Diabetes, Antibodies, Article, 1117 Public Health and Health Services, Endocrinology & Metabolism, 03 medical and health sciences, GLUTAMIC-ACID DECARBOXYLASE, Insulin resistance, Diabetes mellitus, Internal Medicine, medicine, Humans, TYPE-1, Aged, 030304 developmental biology, Science & Technology, business.industry, RECOGNITION, 1103 Clinical Sciences, ADULTS, medicine.disease, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Incident diabetes, Case-Control Studies, Immunology, 1114 Paediatrics and Reproductive Medicine, AUTOANTIBODIES, indident diabetes, business
Abstract: Aims/hypothesis Type 1 and type 2 diabetes differ with respect to pathophysiological factors such as beta cell function, insulin resistance and phenotypic appearance, but there may be overlap between the two forms of diabetes. However, there are relatively few prospective studies that have characterised the relationship between autoimmunity and incident diabetes. We investigated associations of antibodies against the 65 kDa isoform of GAD (GAD65) with type 1 diabetes and type 2 diabetes genetic risk scores and incident diabetes in adults in European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct, a case-cohort study nested in the EPIC cohort. Methods GAD65 antibodies were analysed in EPIC participants (over 40 years of age and free of known diabetes at baseline) by radioligand binding assay in a random subcohort (n = 15,802) and in incident diabetes cases (n = 11,981). Type 1 diabetes and type 2 diabetes genetic risk scores were calculated. Associations between GAD65 antibodies and incident diabetes were estimated using Prentice-weighted Cox regression. Results GAD65 antibody positivity at baseline was associated with development of diabetes during a median follow-up time of 10.9 years (HR for GAD65 antibody positive vs negative 1.78; 95% CI 1.43, 2.20) after adjustment for sex, centre, physical activity, smoking status and education. The genetic risk score for type 1 diabetes but not type 2 diabetes was associated with GAD65 antibody positivity in both the subcohort (OR per SD genetic risk 1.24; 95% CI 1.03, 1.50) and incident cases (OR 1.97; 95% CI 1.72, 2.26) after adjusting for age and sex. The risk of incident diabetes in those in the top tertile of the type 1 diabetes genetic risk score who were also GAD65 antibody positive was 3.23 (95% CI 2.10, 4.97) compared with all other individuals, suggesting that 1.8% of incident diabetes in adults was attributable to this combination of risk factors. Conclusions/interpretation Our study indicates that incident diabetes in adults has an element of autoimmune aetiology. Thus, there might be a reason to re-evaluate the present subclassification of diabetes in adulthood.
Published: 2019

13. Differences in the Impact of COVID-19 on Pathology Laboratories and Cancer Diagnosis in Girona

Author: Arantza Sanvisens, Montse Puigdemont, Jordi Rubió-Casadevall, Anna Vidal-Vila, Eugeni López-Bonet, Ferran Martín-Romero, Rafael Marcos-Gragera, Institut Català de la Salut, [Sanvisens A] Epidemiology Unit and Girona Cancer Registry, Institut de Recerca Contra la Leucèmia Josep Carreras, Girona, Spain. [Puigdemont M, Vidal-Vila, A] Epidemiology Unit and Girona Cancer Registry, Institut Català d'Oncologia, Pla Director d'Oncologia, Girona, Spain. Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta (IDIBGI), Girona, Spain. [Rubió-Casadevall J] Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta (IDIBGI), Girona, Spain. Medical Oncology Department, Institut Català d'Oncologia, Hospital Universitari Dr. Josep Trueta, Girona, Spain. School of Medicine, Universitat de Girona, Girona, Spain. [López-Bonet E] Department d’Anatomia Patològica Hospital Universitari de Girona Dr. Josep Trueta, Institut Català de la Salut (ICS), Girona, Spain [Martín-Romero F] Department of Pathology, Hospital de Figueres, Fundació Salut Empordà, Figueres, Spain. [Marcos-Gragera, R] ]Epidemiology Unit and Girona Cancer Registry, Institut de Recerca Contra la Leucèmia Josep Carreras, Girona, Spain. Epidemiology Unit and Girona Cancer Registry, Institut Català d'Oncologia, Pla Director d'Oncologia, Girona, Spain. Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta (IDIBGI), Girona, Spain. School of Medicine, Universitat de Girona, Girona, Spain, and Hospital Universitari de Girona Dr Josep Trueta
Subjects: diagnosis, Health, Toxicology and Mutagenesis, COVID-19 Pandemic, 2020, COVID-19 (Malaltia), Article, neoplasias [ENFERMEDADES], COVID-19, cancer, pathology, Diagnosis, Pathology, Càncer -- Diagnòstic, virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES], Humans, Pandèmia de COVID-19, 2020, Càncer - Diagnòstic, Melanoma, Pandemics, Cancer, Health Occupations::Medicine::Pathology [DISCIPLINES AND OCCUPATIONS], SARS-CoV-2, Public Health, Environmental and Occupational Health, Cancer -- Diagnosis, Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES], profesiones sanitarias::medicina::anatomía patológica [DISCIPLINAS Y OCUPACIONES], Neoplasms [DISEASES], Medicine, Laboratories, Laboratoris de patologia
Abstract: Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Càncer; Diagnòstic; Patologia Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Cancer; Diagnóstico; Patologia Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Cancer; Diagnosis; Pathology Introduction: The recent COVID-19 pandemic has compromised socio-health care, with consequences for the diagnosis and follow-up of other pathologies. The aim of this study was to evaluate the impact of COVID-19 on cancer diagnosis in Girona, Spain. Methodology: Observational study of samples received in two pathology laboratories during 2019-2020 (tertiary hospital in Girona and county hospital in Figueres). Date, sample type, and location and morphology were available. Samples were recoded to determine malignancy and grouped by location. Comparisons were made by calendar year and period of exposure to COVID-19. Results: 102,360 samples were included: 80,517 from Girona and 21,843 from Figueres. The reduction in activity in the pathology laboratories in 2020 compared to the previous year was 25.4% in Girona and 27.5% in Figueres. The reduction in cancer diagnoses in 2020 compared to 2019 was 6.8% in Girona and 21% in Figueres. In both laboratories, a decrease was observed in the diagnoses of neoplasms of the lip, oral cavity and pharynx, larynx, colon, rectum and anus, kidney and urinary system, melanoma, and central nervous system. A statistically significant higher probability of a sample received in the pathology laboratory displaying malignancy during COVID-19 was found (Girona: OR = 1.28, 95% CI: 1.23-1.34; Figueres: OR = 1.10, 95% CI: 1.01-1.20) with respect to the COVID-19-free period. Conclusions: The COVID-19 pandemic has resulted in a reduction in cancer diagnoses by pathology departments that varies according to tumor location and type of hospital. Despite this, the optimization of care resources and the recovery effort have partially reduced the impact of the pandemic in certain neoplasms. This work was partially funded by the Josep Carreras Leukaemia Research Institute (grant number: FIJC1100) and the Agency for Management of University and Research Grants, Government of Catalonia (grant number: 2017SGR00733)
Published: 2021

14. Dietary fatty acids, macronutrient substitutions, food sources and incidence of coronary heart disease: Findings from the EPIC-CVD case-cohort study across nine european countries

Author: Matthias B. Schulze, Vittorio Krogh, Rosario Tumino, Nita G. Forouhi, Christina C. Dahm, Kim Overvad, Marie-Christine Boutron-Ruault, Angela M. Wood, Yvonne T. van der Schouw, Guri Skeie, Laura Johnson, Fumiaki Imamura, Ivonne Sluijs, José R Quirós, Elisabete Weiderpass, Nicholas J. Wareham, Timothy J. Key, Adam S. Butterworth, Giovanna Masala, Alicia K Heath, Albert Koulman, Conchi Moreno-Iribas, Inge Huybrechts, John Danesh, Stephen J. Sharp, Salvatore Panico, Carlotta Sacerdote, Aurora Perez-Cornago, Olle Melander, Rudolf Kaaks, Elio Riboli, Tammy Y.N. Tong, María José Sánchez, Rajiv Chowdhury, Ju-Sheng Zheng, Miguel Rodríguez-Barranco, W M Monique Verschuren, Marinka Steur, Ingegerd Johansson, Heiner Boeing, Anne Tjønneland, Carmen Santiuste, Antonia Trichopoulou, Maria Wennberg, Jolanda M. A. Boer, Marcela Guevara, Cecilie Kyrø, Raul Zamora-Ros, Liher Imaz, Tilman Kühn, Marianne Uhre Jakobsen, Ulrika Ericson, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, G0800270, MR/L003120/1, Pfizer, AstraZeneca, Kræftens Bekæmpelse, DCS, Deutsches Krebsforschungszentrum, DKFZ, Centre International de Recherche sur le Cancer, CIRC, Merck Sharp and Dohme, MSD, Seventh Framework Programme, FP7: HEALTH-F2-2012-279233, National Research Council, NRC, University of Maryland School of Public Health, SPH, Medical Research Council, MRC: MC_UU_00006/1, National Institute for Health Research, NIHR, British Heart Foundation, BHF: RG/18/13/33946, RG13/13/30194, SP/09/002, Cancer Research UK, CRUK: C8221/A29017, MR/M012190/1, World Cancer Research Fund, WCRF, Imperial College London, European Research Council, ERC: 268834, Institut National de la Santé et de la Recherche Médicale, Inserm, Bundesministerium für Bildung und Forschung, BMBF, Cancerfonden, Ministerie van Volksgezondheid, Welzijn en Sport, VWS, Ligue Contre le Cancer, Vetenskapsrådet, VR, Instituto de Salud Carlos III, ISCIII, European Social Fund, ESF, Sixth Framework Programme, FP6: LSHM_CT_2006_037197, Associazione Italiana per la Ricerca sul Cancro, AIRC, Deutsche Krebshilfe, Akademi Sains Malaysia, ASM: MR/P013880/1, Institut Gustave-Roussy, Mutuelle Générale de l'Education Nationale, MGEN, UCLH Biomedical Research Centre, NIHR BRC: BRC-1215-20014, NIHR Imperial Biomedical Research Centre, BRC, Hellenic Health Foundation, HHF: CP15/00100, IS-BRC-1215-20014, MC_UU_00006/3, Dr Danesh reports grants, personal fees and non-financial support from Merck Sharp & Dohme, grants, personal fees, and nonfinancial support from Novartis, grants from Pfizer, and grants from AstraZeneca outside the submitted work. He is member of the International Cardiovascular and Metabolic Advisory Board for Novartis (since 2010), the Steering Committee of UK Biobank (since 2011), the MRC International Advisory Group (ING) member, London (since 2013), the MRC High Throughput Science ‘Omics Panel Member, London (since 2013), the Scientific Advisory Committee for Sanofi (since 2013), the International Cardiovascular and Metabolism Research and Development Portfolio Committee for Novartis, and the Astra Zeneca Genomics Advisory Board (2018). Dr Butterworth reports grants outside of this work from AstraZeneca, Biogen, BioMarin, Bioverativ, Merck, Novartis, Pfizer, and Sanofi and personal fees from Novartis. The remaining authors have no disclosures to report., EPIC-CVD was supported by the European Commission Framework Programme 7 (HEALTH-F2-2012-279233), and the European Research Council (268834). The coordinating center was supported by core funding from the: United Kingdom MRC (G0800270, MR/L003120/1), British Heart Foundation (BHF) (SP/09/002, RG13/13/30194, RG/18/13/33946), and National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (BRC) (BRC-1215-20014).* The establishment of the study subcohort was supported by the European Union Sixth Framework Programme (grant LSHM_CT_2006_037197 to the InterAct project) and the MRC Epidemiology Unit (grant MC_UU_00006/1). The coordination of EPIC is financially supported by International Agency for Research on Cancer and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, which has additional infrastructure support provided by NIHR Imperial BRC. The national cohorts are supported by: Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (France), German Cancer Aid, German Cancer Research Center, German Institute of Human Nutrition Potsdam-Rehbruecke, Federal Ministry of Education and Research (Germany), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports, Netherlands Cancer Registry, LK Research Funds, Dutch Prevention Funds, Zorg Onderzoek Nederland, World Cancer Research Fund, Statistics Netherlands (the Netherlands), Health Research Fund– Instituto de Salud Carlos III, Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), Cancer Research UK (14136 to EPIC-Norfolk, C8221/A29017 to EPIC-Oxford), MRC (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom). EPIC-Greece was supported by the Hellenic Health Foundation (Greece). M.S., N.J.W., N.G.F., and F.I. acknowledge support from MRC Epidemiology Unit (MC_UU_00006/1 and MC_UU_00006/3). N.J.W. and N.G.F. acknowledge support from NIHR* Cambridge BRC: Nutrition, Diet, and Lifestyle Research Theme (IS-BRC-1215-20014) and NGF is a NIHR Senior Investigator Award holder. M.S. was also supported by BHF for part of this work while working in the BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom. R.Z.-R. thanks the 'Miguel Servet' program (CP15/00100) from the Institute of Health Carlos III (co-funded by the European Social Fund–European Social Fund Investing in Your Future). A.W. was supported by a BHF-Turing Cardiovascular Data Science Award and by the European Commission-Innovative Medicines Initiative (BigData@Heart). R.C. was funded by a MRC-Newton project grant to study genetic risk factors of cardiovascular disease among Southeast Asian people and the Academy of Sciences Malaysia (grant no. MR/P013880/1) and a United Kingdom Research and Innovation-Global Challenges Research Fund Project Grant to study risk factors of noncommunicable diseases in Bangladesh. J.D. holds a BHF Professorship and a NIHR Senior Investigator Award., Steur, Marinka [0000-0002-9028-0290], Imamura, Fumiaki [0000-0002-6841-8396], Key, Timothy J [0000-0003-2294-307X], Chowdhury, Rajiv [0000-0003-4881-5690], Guevara, Marcela [0000-0001-9242-6364], Jakobsen, Marianne U [0000-0001-6518-4136], Johansson, Ingegerd [0000-0002-9227-8434], Weiderpass, Elisabete [0000-0003-2237-0128], Boer, Jolanda MA [0000-0002-9714-4304], Boutron-Ruault, Marie-Christine [0000-0002-5956-5693], Heath, Alicia K [0000-0001-6517-1300], Huybrechts, Inge [0000-0003-3838-855X], Imaz, Liher [0000-0002-3777-4953], Masala, Giovanna [0000-0002-5758-9069], Zamora-Ros, Raul [0000-0002-6236-6804], Perez-Cornago, Aurora [0000-0002-5652-356X], Tong, Tammy YN [0000-0002-0284-8959], Wareham, Nicholas J [0000-0003-1422-2993], Forouhi, Nita G [0000-0002-5041-248X], and Apollo - University of Cambridge Repository
Subjects: Saturated fat, Physiology, Coronary Disease, 030204 cardiovascular system & hematology, EPIC, Cohort Studies, 0302 clinical medicine, Medicine, Cardiac and Cardiovascular Systems, 030212 general & internal medicine, 1102 Cardiorespiratory Medicine and Haematology, 2. Zero hunger, chemistry.chemical_classification, Nutrition and Dietetics, Kardiologi, Primary prevention, Incidence, Incidence (epidemiology), Fatty Acids, Fatty acids in human nutrition, 3. Good health, Europe, Näringslära, Coronary heart disease, Dietary guidelines, Cardiology and Cardiovascular Medicine, Polyunsaturated fatty acid, Cohort study, Malalties coronàries, 03 medical and health sciences, SDG 3 - Good Health and Well-being, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Àcids grassos en la nutrició, Diseases of the circulatory (Cardiovascular) system, Humans, Nutritional epidemiology, business.industry, Nutrients, Dietary Fats, chemistry, Food, RC666-701, SPS Exercise, Nutrition and Health Sciences, business
Abstract: EPIC-CVD was supported by the European Commission Framework Programme 7 (HEALTH-F2-2012-279233), and the European Research Council (268834). The coordinating center was supported by core funding from the: United Kingdom MRC (G0800270; MR/L003120/1), British Heart Foundation (BHF) (SP/09/002; RG13/13/30194; RG/18/13/33946), and National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (BRC) (BRC-1215-20014).* The establishment of the study subcohort was supported by the European Union Sixth Framework Programme (grant LSHM_CT_ 2006_037197 to the InterAct project) and the MRC Epidemiology Unit (grant MC_UU_00006/1). The coordination of EPIC is financially supported by International Agency for Research on Cancer and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, which has additional infrastructure support provided by NIHR Imperial BRC. The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (France); German Cancer Aid, German Cancer Research Center, German Institute of Human Nutrition Potsdam-Rehbruecke, Federal Ministry of Education and Research (Germany); Associazione Italiana per la Ricerca sul Cancro--AIRC--Italy, Compagnia di SanPaolo and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports, Netherlands Cancer Registry, LK Research Funds, Dutch Prevention Funds, Zorg Onderzoek Nederland, World Cancer Research Fund, Statistics Netherlands (the Netherlands); Health Research Fund-Instituto de Salud Carlos III, Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skane and Vasterbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C8221/A29017 to EPIC-Oxford), MRC (1000143 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford) (United Kingdom). EPIC-Greece was supported by the Hellenic Health Foundation (Greece). M.S., N.J.W., N.G.F., and F.I. acknowledge support from MRC Epidemiology Unit (MC_UU_ 00006/1 and MC_UU_00006/3). N.J.W. and N.G.F. acknowledge support from NIHR* Cambridge BRC: Nutrition, Diet, and Lifestyle Research Theme (IS-BRC-1215--20014) and NGF is a NIHR Senior Investigator Award holder. M.S. was also supported by BHF for part of this work while working in the BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom. R. Z.-R. thanks the "Miguel Servet" program (CP15/00100) from the Institute of Health Carlos III (co-funded by the European Social Fund--European Social Fund Investing in Your Future). A.W. was supported by a BHF-Turing Cardiovascular Data Science Award and by the European Commission-Innovative Medicines Initiative (BigData@Heart).R.C.was funded by a MRC-Newton project grant to study genetic risk factors of cardiovascular disease among Southeast Asian people and the Academy of Sciences Malaysia (grant no. MR/P013880/1) and a United Kingdom Research and Innovation-Global Challenges Research Fund Project Grant to study risk factors of noncommunicable diseases in Bangladesh. J.D. holds a BHF Professorship and a NIHR Senior Investigator Award. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy, or views of the International Agency for Research on Cancer/World Health Organization. The funders of the study had no role in study design, data collection, analysis, data interpretation, or writing of the article, or in the decision to submit for publication. M.S. had full access to all the data in the study, and M.S. and N.G.F. had final responsibility for the decision to submit for publication., BACKGROUND: There is controversy about associations between total dietary fatty acids, their classes (saturated fatty acids [SFAs], monounsaturated fatty acids, and polyunsaturated fatty acids), and risk of coronary heart disease (CHD). Specifically, the relevance of food sources of SFAs to CHD associations is uncertain. METHODS AND RESULTS: We conducted a case-cohort study involving 10 529 incident CHD cases and a random subcohort of 16 730 adults selected from a cohort of 385 747 participants in 9 countries of the EPIC (European Prospective Investigation into Cancer and Nutrition) study. We estimated multivariable adjusted country-specific hazard ratios (HRs) and 95% CIs per 5% of energy intake from dietary fatty acids, with and without isocaloric macronutrient substitutions, using Prentice-weighted Cox regression models and pooled results using random-effects meta-analysis. We found no evidence for associations of the consumption of total or fatty acid classes with CHD, regardless of macronutrient substitutions. In analyses considering food sources, CHD incidence was lower per 1% higher energy intake of SFAs from yogurt (HR, 0.93 [95% CI, 0.88–0.99]), cheese (HR, 0.98 [95% CI, 0.96–1.00]), and fish (HR, 0.87 [95% CI, 0.75–1.00]), but higher for SFAs from red meat (HR, 1.07 [95% CI, 1.02–1.12]) and butter (HR, 1.02 [95% CI, 1.00–1.04]). CONCLUSIONS: This observational study found no strong associations of total fatty acids, SFAs, monounsaturated fatty acids, and polyunsaturated fatty acids, with incident CHD. By contrast, we found associations of SFAs with CHD in opposite directions dependent on the food source. These findings should be further confirmed, but support public health recommendations to consider food sources alongside the macronutrients they contain, and suggest the importance of the overall food matrix., European Commission Framework Programme 7 HEALTH-F2-2012-279233, European Research Council (ERC), European Commission 268834, UK Research & Innovation (UKRI), Medical Research Council UK (MRC) G0800270 MR/L003120/1, British Heart Foundation SP/09/002 RG13/13/30194 RG/18/13/33946, National Institute for Health Research (NIHR) BRC-1215-20014, European Commission LSHM_CT_ 2006_037197, Medical Research Council UK (MRC) MC_UU_ 00006/1 MC_UU_00006/3, International Agency for Research on Cancer, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Danish Cancer Society, Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (France), German Cancer Aid, German Cancer Research Center, German Institute of Human Nutrition Potsdam, Rehbruecke, Federal Ministry of Education and Research (Germany), Fondazione AIRC per la ricerca sul cancro, Compagnia di San Paolo, Dutch Ministry of Public Health, Welfare and Sports, Netherlands Cancer Registry, LK Research Funds, Dutch Prevention Funds, Zorg Onderzoek Nederland, World Cancer Research Fund International (WCRF), Netherlands Government, Instituto de Salud Carlos III, Junta de Andalucia, Regional Government of Asturias, Basque Government, Regional Government of Murcia, Regional Government of Navarra, Catalan Institute of Oncology (Spain), Swedish Cancer Society, County Council of Skane (Sweden), County Council of Vasterbotten (Sweden), Cancer Research UK 14136 C8221/A29017, Medical Research Council UK (MRC) 1000143 MR/M012190/1, Hellenic Health Foundation (Greece), NIHR* Cambridge BRC: Nutrition, Diet, and Lifestyle Research Theme IS-BRC-1215-20014, British Heart Foundation, Institute of Health Carlos III (European Social Fund-European Social Fund Investing in Your Future) CP15/00100, BHF-Turing Cardiovascular Data Science Award, European Commission-Innovative Medicines Initiative (BigData@Heart), MRC-Newton project grant MR/P013880/1, United Kingdom Research and Innovation-Global Challenges Research Fund, NIHR Senior Investigator Award
Published: 2021

15. The COVID-19 pandemic and the menstrual cycle: research gaps and opportunities

Author: Gemma C Sharp, Abigail Fraser, Gemma Sawyer, Gabriella Kountourides, Kayleigh E Easey, Gemma Ford, Zuzanna Olszewska, Laura D Howe, Deborah A Lawlor, Alexandra Alvergne, Jacqueline A Maybin, Bristol Medical School, University of Bristol [Bristol], MRC Integrative Epidemiology Unit, Population Health Sciences, University of Bristol [Bristol]-University of Bristol [Bristol]-Bristol Medical School, University of Bristol [Bristol]-University of Bristol [Bristol], NIHR Bristol Biomedical Research Centre, School of Anthropology, MRC Integrative Epidemiology Unit [Bristol, Royaume-Uni] (MRC IEU), NIHR Bristol Biomedical Research, Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche pour le développement [IRD] : UR226, School of Anthropology and Museum Ethnography, University of Oxford, MRC Centre for Reproductive Health, University of Edinburgh, Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École Pratique des Hautes Études (EPHE), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS)
Subjects: Opinion, 030219 obstetrics & reproductive medicine, SARS-CoV-2, Epidemiology, [SDV]Life Sciences [q-bio], COVID-19, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, General Medicine, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, 5. Gender equality, Humans, AcademicSubjects/MED00860, Female, 030212 general & internal medicine, Pandemics, Menstrual Cycle
Abstract: International audience; Since the beginning of the COVID-19 pandemic, discussions on social media and blogs have indicated that women have experienced menstrual changes, including altered menstrual duration, frequency, regularity, and volume (heavier bleeding and clotting), increased dysmenorrhea, and worsened premenstrual syndrome. There have been a small number of scientific studies of variable quality reporting on menstrual cycle features during the pandemic, but it is still unclear whether apparent changes are due to COVID-19 infection/illness itself, or other pandemic-related factors like increased psychological stress and changes in health behaviours. It is also unclear to what degree current findings are explained by reporting bias, recall bias, selection bias and confounding factors. Further research is urgently needed. We provide a list of outstanding research questions and potential approaches to address them. Findings can inform policies to mitigate against gender inequalities in health and society, allowing us to build back better post-COVID.
Published: 2021

16. Discovery of common and rare genetic risk variants for colorectal cancer

Author: Charles M. Connolly, Deborah A. Nickerson, Jian Gong, Sébastien Küry, Barbara Pardini, Brent W. Zanke, Andrea Gsur, Jochen Hampe, Coral Arnau-Collell, M. Henar Alonso, Elio Riboli, Annika Lindblom, Ulrike Peters, Gad Rennert, Tabitha A. Harrison, Lori C. Sakoda, Caroline McNeil, Flavio Lejbkowicz, Hyun Min Kang, David J. Hunter, Martha L. Slattery, Miguel Rodríguez-Barranco, Christina Bamia, Satu Männistö, Timothy J. Key, W. James Gauderman, Gonçalo R. Abecasis, Sanford D. Markowitz, Laurence N. Kolonel, Mark A. Jenkins, Yi Lin, Robin Myte, Hedy S. Rennert, Neil Murphy, Antonia Trichopoulou, Christopher I. Li, Ross L. Prentice, Sai Chen, Stephanie J. Weinstein, Kristin E. Anderson, Hua Ling, Mitul Shah, Philipp Hofer, Wen Yi Huang, Sergi Castellví-Bel, Susanna C. Larsson, Maria Dolores Chirlaque, Wei Zheng, Stephanie L. Schmit, Cecelia A. Laurie, Soo-Chin Lee, David Forman, Andrea N. Burnett-Hartman, Giovanna Masala, Sarah C. Nelson, Michael O. Woods, Charles Kooperberg, Qing Zhang, Sonja I. Berndt, Christopher S. Carlson, Katja Butterbach, Hyeong Rok Kim, Rebecca D. Jackson, David Van Den Berg, Michael C. Bassik, Amanda J. Cross, Sushma S. Thomas, Clemens Schafmayer, Anna H. Wu, Douglas F. Easton, Robert W. Haile, Ludmila Vodickova, Graham G. Giles, Yu Ru Su, Jenny Chang-Claude, Lorena Moreno, Peter C. Scacheri, Stefanie Brezina, Min-Ho Shin, Steven Gallinger, Bethany Van Guelpen, Daniel D. Buchanan, Roger L. Milne, Stephen J. Chanock, Tin Louie, Tameka Shelford, Emily White, Kala Visvanathan, Loic Le Marchand, Veronika Vymetalkova, Roxann G. Ingersoll, Temitope O. Keku, Stephanie A. Bien, Fredrick R. Schumacher, Wan-Ling Hsu, Amanda E. Toland, John S. Grove, Noralane M. Lindor, Faye Elliott, Leon Raskin, Heather Hampel, Joshua D. Smith, Vicente Martín, David V. Conti, Sjoerd G. Elias, Henk J. van Kranen, Manish Gala, Daniela Seminara, Syed H.E. Zaidi, Suzanne M. Leal, Tilman Kühn, Korbinian Weigl, Marc J. Gunter, Cornelia M. Ulrich, Peyton Greenside, Victor Moreno, John D. Potter, Michael Hoffmeister, Eric J. Jacobs, Catherine M. Tangen, Jihyoun Jeon, Fränzel J.B. Van Duijnhoven, Andrew T. Chan, Stephen B. Gruber, John A. Baron, Alicja Wolk, Edith J. M. Feskens, Demetrius Albanes, Amit Joshi, Bette J. Caan, Polly A. Newcomb, Stéphane Bézieau, Elizabeth M. Gillanders, Anshul Kundaje, Elizabeth A. Platz, Michael Wainberg, Sun-Seog Kweon, C. Roland Wolf, Gemma Ibáñez-Sanz, Shuji Ogino, Emiko Kobayashi, Richard B. Hayes, Patrick S. Parfrey, Katarina Cuk, Stephen N. Thibodeau, Kenneth Offit, David Duggan, Sophia Harlid, Pavel Vodicka, Juergen Boehm, Christa Stegmaier, Jeroen R. Huyghe, Joseph Vijai, Sang-Hee Cho, Elizabeth W. Pugh, Rachel Pearlman, Alessio Naccarati, Marilena Melas, Graham Casey, Jane Romm, Stephan Buch, Phyllis J. Goodman, Albert de la Chapelle, John L. Hopper, Zsofia K. Stadler, Corinne E. Joshu, Liesel M. FitzGerald, Wolfgang Lieb, Aung Ko Win, Keith R. Curtis, Hermann Brenner, Christopher K. Edlund, Li Hsu, Conghui Qu, Peter T. Campbell, Robert E. Schoen, Heiner Boeing, D. Timothy Bishop, Kimberly F. Doheny, Sabina Sieri, Barbara L. Banbury, Mathieu Lemire, Jane C. Figueiredo, Gregory Idos, Katerina Shulman, Thomas J. Hudson, Melissa C. Southey, Duncan C. Thomas, Paul D.P. Pharoah, Mila Pinchev, Vittorio Perduca, Rocky Fischer, Volker Arndt, William M. Grady, Nasa Sinnott-Armstrong, N. Charlotte Onland-Moret, David M. Levine, Li Li, Dallas R. English, Health Research Board - Ireland, Department of Medical Genetics, HMNC Brain Health, Case Western Reserve University [Cleveland], National Cancer Institute, NIH, Division of Clinical Epidemiology and Aging Research, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Service de Génétique, Centre hospitalier universitaire de Nantes (CHU Nantes), Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Division of Cancer Epidemiology, Cancer Genome Project, The Wellcome Trust Sanger Institute [Cambridge], Division of Signaling Biology, Ontario Cancer Institute, Consorcio de Investigación Biomédica en Red especializado en Epidemiología y Salud Pública (CIBERESP), Los Centros de Investigación Biomédica en Red (CIBER), National Institute of Standards and Technology [Gaithersburg] (NIST), Ohio State University [Columbus] (OSU), Centre for Cancer Genetic Epidemiology, University of Cambridge [UK] (CAM), Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, Cancer Epidemiology Centre, Cancer Council Victoria, Division of Human Nutrition, Wageningen University and Research [Wageningen] (WUR), Division of Public Health Sciences, Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Northern and Yorkshire Cancer Registry and Information Service, Familial Gastrointestinal Cancer Registry, Mount Sinai Hospital [Toronto, Canada] (MSH), University of Melbourne, Nutrition and Metabolism Section, International Agency for Cancer Research (IACR), Department of Internal Medicine I, University Hospital Schleswig-Holstein, Campus Kiel, London School of Hygiene and Tropical Medicine (LSHTM), Fraunhofer Institute for Manufacturing Engineering and Automation (Fraunhofer IPA), Fraunhofer (Fraunhofer-Gesellschaft), Centre for Molecular , Environmental, Genetic and Analytic (MEGA) Epidemiology, University of Melbourne-Centre for Molecular, Melbourne School of Population Health, Department of Mathematics, University of Warwick, Warwick Mathematics Institute (WMI), University of Warwick [Coventry]-University of Warwick [Coventry], Department of Statistics, Penn State University, University of Pennsylvania [Philadelphia], Tata Memorial Centre, Cancer Epidemiology Unit, University of Oxford [Oxford], Thermo Fisher Scientific, Thermo Fisher Scientific Inc., Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Baylor University-Baylor University, National University Health System, Department of Community Medicine and Epidemiology, CHS National Cancer Control Center, Ontario Institute for Cancer Research [Canada] (OICR), Ontario Institute for Cancer Research, Laboratoire de Génie Electrique de Grenoble (G2ELab), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Chronic Disease Epidemiology and Prevention Unit, National Institute for Health and Welfare [Helsinki], Dell-EMC, Molecular and Nutritional Epidemiology Unit (ISPO), Cancer Research and Prevention Institute, Clinical Genetics Service, Memorial Sloane Kettering Cancer Center [New York], Department of Pathology, Brigham and Women's Hospital [Boston], University Medical Center [Utrecht], Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Université Paris Descartes - Paris 5 (UPD5)-Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS), Department of Oncology, Department of Epidemiology and Biostatistics, Imperial College London, Department of Visceral and Thoracic Surgery [Kiel, Germany], University Hospital Schleswig-Holstein [Kiel, Germany], Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, entre for Molecular, Environmental, Genetic and Analytic (MEGA) Epidemiology, Department of Laboratory Medicine and Department of Pathology, Mayo Clinic College of Medicine, Department of Molecular Virology, Immunology and Medical Genetics [Colombus], Ohio State University [Columbus] (OSU)-College of Medicine and Public Health [Colombus], Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School [Athens], Department of Medical Biosciences and Pathology, Umeå University, Institute of Experimental Medicine, Czech Academy of Sciences [Prague] (CAS), Dundee Technopole, CXR Biosciences Ltd, Karolinska Institutet [Stockholm], CINTRA / SEEE Nanyang Technological University, Nanyang Technological University [Singapour], Center for Astrophysical Sciences [Baltimore], Johns Hopkins University (JHU), Computer Science and Artificial Intelligence Laboratory (CSAIL), Massachusetts Institute of Technology (MIT), Department of Preventive Medicine, University of Southern California (USC), Biomedical Research Centre Network for Rare Diseases, CIBER de Enfermedades Raras (CIBERER), Medstar Research Institute, Department of Genome Sciences [Seattle] (GS), University of Washington [Seattle], Department of Internal Medicine, Epidemiology, Human Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Wageningen University and Research Centre [Wageningen] (WUR), Mount Sinai Hospital (MSH), Fraunhofer Institute for Manufacturing Engineering and Automation [Stuttgart] (IPA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Czech Academy of Sciences [Prague] (ASCR), Huyghe, Jeroen R [0000-0001-6027-9806], Harrison, Tabitha A [0000-0002-4173-7530], Chen, Sai [0000-0003-3106-5643], Schmit, Stephanie L [0000-0001-5931-1194], Jeon, Jihyoun [0000-0001-7003-3412], Schumacher, Fredrick R [0000-0002-3073-7463], Nelson, Sarah C [0000-0002-2109-6465], Sinnott-Armstrong, Nasa A [0000-0003-4490-0601], Alonso, M Henar [0000-0003-0285-5451], Arndt, Volker [0000-0001-9320-8684], Bézieau, Stéphane [0000-0003-0095-1319], Bishop, D Timothy [0000-0002-8752-8785], Brezina, Stefanie [0000-0001-5238-6900], Buchanan, Daniel D [0000-0003-2225-6675], Chanock, Stephen J [0000-0002-2324-3393], de la Chapelle, Albert [0000-0001-9345-9248], Easton, Douglas F [0000-0003-2444-3247], Hampe, Jochen [0000-0002-2421-6127], Hayes, Richard B [0000-0002-0918-661X], Hofer, Philipp [0000-0003-2550-6019], Huang, Wen-Yi [0000-0002-4440-3368], Hudson, Thomas J [0000-0002-1376-4849], Jacobs, Eric J [0000-0002-8458-7659], Jenkins, Mark A [0000-0002-8964-6160], Joshi, Amit D [0000-0001-7581-6934], Küry, Sébastien [0000-0001-5497-0465], Larsson, Susanna C [0000-0003-0118-0341], Laurie, Cecelia A [0000-0001-6569-2501], Martín, Vicente [0000-0003-0552-2804], Masala, Giovanna [0000-0002-5758-9069], Milne, Roger L [0000-0001-5764-7268], Naccarati, Alessio [0000-0001-5774-0905], Newcomb, Polly A [0000-0001-8786-0043], Pardini, Barbara [0000-0001-9571-4257], Perduca, Vittorio [0000-0003-0339-0473], Pharoah, Paul DP [0000-0001-8494-732X], Raskin, Leon [0000-0003-1195-7214], Rennert, Gad [0000-0002-8512-068X], Shin, Min-Ho [0000-0002-2217-5624], Toland, Amanda E [0000-0002-0271-1792], Vijai, Joseph [0000-0002-7933-151X], Weigl, Korbinian [0000-0003-4453-2036], Win, Aung Ko [0000-0002-2794-5261], Wolk, Alicja [0000-0001-7387-6845], Zheng, Wei [0000-0003-1226-070X], Bassik, Michael C [0000-0001-5185-8427], Moreno, Victor [0000-0002-2818-5487], Peters, Ulrike [0000-0001-5666-9318], and Apollo - University of Cambridge Repository
Subjects: Male, Nutrition and Disease, Colorectal cancer, IDENTIFIES 6, Genome-wide association study, 0302 clinical medicine, Risk Factors, Voeding en Ziekte, Genotype, ComputingMilieux_MISCELLANEOUS, Avaluació del risc per la salut, Genetics & Heredity, Genetics, 0303 health sciences, COLON-CANCER, 11 Medical And Health Sciences, Middle Aged, 3. Good health, Medical genetics, Female, RNA, Long Noncoding, Colorectal Neoplasms, Life Sciences & Biomedicine, Signal Transduction, EXPRESSION, medicine.medical_specialty, SUSCEPTIBILITY LOCI, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Polymorphism, Single Nucleotide, Article, Health risk assessment, 03 medical and health sciences, QUALITY-CONTROL, Càncer colorectal, Journal Article, medicine, Life Science, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, METAANALYSIS, VLAG, Aged, 030304 developmental biology, Global Nutrition, [SDV.GEN]Life Sciences [q-bio]/Genetics, Wereldvoeding, Science & Technology, ORGAN SIZE, MUTATIONS, Haplotype, Case-control study, 06 Biological Sciences, medicine.disease, Genetic architecture, Case-Control Studies, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Human genome, LYSOPHOSPHATIDIC ACID, 030217 neurology & neurosurgery, Developmental Biology, Genome-Wide Association Study
Abstract: To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P, Reporting Summary. Further information on experimental design is available in the Life Sciences Reporting Summary linked to this article.
Published: 2018

17. Comorbidities at Diagnosis, Survival, and Cause of Death in Patients with Chronic Lymphocytic Leukemia: A Population-Based Study

Author: Villavicencio, Alicia, Solans, Marta, Zacarías-Pons, Lluís, Vidal, Anna, Puigdemont, Montse, Roncero, Josep Maria, Saez, Marc, Marcos-Gragera, Rafael, Universitat Autònoma de Barcelona, Institut Català de la Salut, [Villavicencio A] Epidemiology Unit and Girona Cancer Registry, Oncology Coordination Plan, Catalan Institute of Oncology, Girona, Spain. Research Group on Statistics, Econometrics and Health (GRECS), University of Girona, Girona, Spain. Descriptive Epidemiology, Genetics and Cancer Prevention Group, Biomedical Research Institute (IDIBGI), Girona, Spain. [Solans M] Research Group on Statistics, Econometrics and Health (GRECS), University of Girona, Girona, Spain. Descriptive Epidemiology, Genetics and Cancer Prevention Group, Biomedical Research Institute (IDIBGI), Girona, Spain. Centro de Investigación Biomédica en Red: Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Zacarías-Pons Ll] Research Group on Aging, Disability and Health, Girona Biomedical Research Institute (IDIBGI), Girona, Spain. [Vidal A, Puigdemont M] Epidemiology Unit and Girona Cancer Registry, Oncology Coordination Plan, Catalan Institute of Oncology, Girona, Spain. Descriptive Epidemiology, Genetics and Cancer Prevention Group, Biomedical Research Institute (IDIBGI), Girona, Spain. [Roncero JM] Departament d’Hematologia, Hospital Universitari de Girona Doctor Josep Trueta, Institut Català de la Salut (ICS), Girona, Spain. [Saez M] Research Group on Statistics, Econometrics and Health (GRECS), University of Girona, Girona, Spain. Centro de Investigación Biomédica en Red: Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Marcos-Gragera R] Epidemiology Unit and Girona Cancer Registry, Oncology Coordination Plan, Catalan Institute of Oncology, Girona, Spain. Research Group on Statistics, Econometrics and Health (GRECS), University of Girona, Girona, Spain. Descriptive Epidemiology, Genetics and Cancer Prevention Group, Biomedical Research Institute (IDIBGI), Girona, Spain. Centro de Investigación Biomédica en Red: Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. Josep Carreras Leukemia Research Institute, Badalona, Spain, and Hospital Universitari de Girona Dr Josep Trueta
Subjects: Multivariate analysis, Other subheadings::Other subheadings::/epidemiology [Other subheadings], Health, Toxicology and Mutagenesis, Chronic lymphocytic leukemia, lcsh:Medicine, Comorbidity, 0302 clinical medicine, immune system diseases, Cause of Death, hemic and lymphatic diseases, Medicine, ambiente y salud pública::salud pública::factores epidemiológicos::comorbilidad [ATENCIÓN DE SALUD], Cause of death, education.field_of_study, Leucèmia limfoide, Relative survival, Otros calificadores::Otros calificadores::/epidemiología [Otros calificadores], Leucèmia limfoide - Epidemiologia, Leucèmia limfoide -- Mortalitat, 030220 oncology & carcinogenesis, neoplasias::neoplasias por tipo histológico::leucemia::leucemia linfoide::leucemia de células B::leucemia linfocítica crónica de células B [ENFERMEDADES], medicine.medical_specialty, Population, Mort - Causes, causes of death, comorbidities, survival, Article, 03 medical and health sciences, Comorbiditat, Diabetes mellitus, Internal medicine, Humans, Health Care Quality, Access, and Evaluation::Quality of Health Care::Epidemiologic Factors::Comorbidity [HEALTH CARE], education, Proportional Hazards Models, business.industry, lcsh:R, Public Health, Environmental and Occupational Health, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, Cancer registry, population-based, Lymphocytic leukemia, Neoplasms::Neoplasms by Histologic Type::Leukemia::Leukemia, Lymphoid::Leukemia, B-Cell::Leukemia, Lymphocytic, Chronic, B-Cell [DISEASES], Investigative Techniques::Epidemiologic Methods::Data Collection::Vital Statistics::Mortality::Cause of Death [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Lymphocytic leukemia -- Mortality, Spain, chronic lymphocytic leukemia, business, técnicas de investigación::métodos epidemiológicos::recopilación de datos::estadísticas vitales::mortalidad::causas de muerte [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], 030215 immunology
Abstract: This study aimed to examine the prevalence of comorbidities in patients diagnosed with chronic lymphocytic leukemia (CLL), and to assess its influence on survival and cause-specific mortality at a population-based level. Incident CLL cases diagnosed in the Girona province (Spain) during 2008&ndash, 2016 were extracted from the Girona Cancer Registry. Rai stage and presence of comorbidities at diagnosis, further categorized using the Charlson comorbidity index (CCI), were obtained from clinical records. Observed (OS) and relative survival (RS) were estimated and Cox&rsquo, s proportional hazard models were used to explore the impact of comorbidity on mortality. Among the 400 cases included in the study, 380 (99.5%) presented at least one comorbidity at CLL diagnosis, with diabetes without end organ damage (21%) being the most common disease. 5-year OS and RS were 68.8 (95% CI: 64.4&ndash, 73.6) and 99.5 (95% CI 3.13&ndash, 106.0), respectively, which decreased markedly with increasing CCI, particularly in patients with CCI &ge, 3. Multivariate analysis identified no statistically significant association between the CCI and overall CLL-related or CLL-unrelated mortality. In conclusion, a high CCI score negatively influenced the OS and RS of CLL patients, yet its effect on mortality was statistically non-significant when also considering age and the Rai stage.
Published: 2021
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18. Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Author: Shah, Sonia, Henry, Albert, Roselli, Carolina, Lin, Honghuang, Sveinbjornsson, Gardar, Fatemifar, Ghazaleh, Hedman, Asa K, Wilk, Jemma B, Morley, Michael P, Chaffin, Mark D, Helgadottir, Anna, Verweij, Niek, Dehghan, Abbas, Almgren, Peter, Andersson, Charlotte, Aragam, Krishna G, Arnlov, Johan, Backman, Joshua D, Biggs, Mary L, Bloom, Heather L, Brandimarto, Jeffrey, Brown, Michael R, Buckbinder, Leonard, Carey, David J, Chasman, Daniel I, Chen, Xing, Chen, Xu, Chung, Jonathan, Chutkow, William, Cook, James P, Delgado, Graciela E, Denaxas, Spiros, Doney, Alexander S, Doerr, Marcus, Dudley, Samuel C, Dunn, Michael E, Engstrom, Gunnar, Esko, Tonu, Felix, Stephan B, Finan, Chris, Ford, Ian, Ghanbari, Mohsen, Ghasemi, Sahar, Giedraitis, Vilmantas, Giulianini, Franco, Gottdiener, John S, Gross, Stefan, Gudbjartsson, Daniel F, Gutmann, Rebecca, Haggerty, Christopher M, van der Harst, Pim, Hyde, Craig L, Ingelsson, Erik, Jukema, J Wouter, Kavousi, Maryam, Khaw, Kay-Tee, Kleber, Marcus E, Kober, Lars, Koekemoer, Andrea, Langenberg, Claudia, Lind, Lars, Lindgren, Cecilia M, London, Barry, Lotta, Luca A, Lovering, Ruth C, Luan, Jian'an, Magnusson, Patrik, Mahajan, Anubha, Margulies, Kenneth B, Maerz, Winfried, Melander, Olle, Mordi, Ify R, Morgan, Thomas, Morris, Andrew D, Morris, Andrew P, Morrison, Alanna C, Nagle, Michael W, Nelson, Christopher P, Niessner, Alexander, Niiranen, Teemu, O'Donoghue, Michelle L, Owens, Anjali T, Palmer, Colin NA, Parry, Helen M, Perola, Markus, Portilla-Fernandez, Eliana, Psaty, Bruce M, Rice, Kenneth M, Ridker, Paul M, Romaine, Simon PR, Rotter, Jerome I, Salo, Perttu, Salomaa, Veikko, van Setten, Jessica, Shalaby, Alaa A, Smelser, Diane T, Smith, Nicholas L, Stender, Steen, Stott, David J, Svensson, Per, Tammesoo, Mari-Liis, Taylor, Kent D, Teder-Laving, Maris, Teumer, Alexander, Thorgeirsson, Gudmundur, Thorsteinsdottir, Unnur, Torp-Pedersen, Christian, Trompet, Stella, Tyl, Benoit, Uitterlinden, Andre G, Veluchamy, Abirami, Voelker, Uwe, Voors, Adriaan A, Wang, Xiaosong, Wareham, Nicholas J, Waterworth, Dawn, Weeke, Peter E, Weiss, Raul, Wiggins, Kerri L, Xing, Heming, Yerges-Armstrong, Laura M, Yu, Bing, Zannad, Faiez, Zhao, Jing Hua, Hemingway, Harry, Samani, Nilesh J, McMurray, John JV, Yang, Jian, Visscher, Peter M, Newton-Cheh, Christopher, Malarstig, Anders, Holm, Hilma, Lubitz, Steven A, Sattar, Naveed, Holmes, Michael V, Cappola, Thomas P, Asselbergs, Folkert W, Hingorani, Aroon D, Kuchenbaecker, Karoline, Ellinor, Patrick T, Lang, Chim C, Stefansson, Kari, Smith, J Gustav, Vasan, Ramachandran S, Swerdlow, Daniel I, Lumbers, R Thomas, Abecasis, Goncalo, Backman, Joshua, Bai, Xiaodong, Balasubramanian, Suganthi, Banerjee, Nilanjana, Baras, Aris, Barnard, Leland, Beechert, Christina, Blumenfeld, Andrew, Cantor, Michael, Chai, Yating, Coppola, Giovanni, Damask, Amy, Dewey, Frederick, Economides, Aris, Eom, Gisu, Forsythe, Caitlin, Fuller, Erin D, Gu, Zhenhua, Gurski, Lauren, Guzzardo, Paloma M, Habegger, Lukas, Hahn, Young, Hawes, Alicia, van Hout, Cristopher, Jones, Marcus B, Khalid, Shareef, Lattari, Michael, Li, Alexander, Lin, Nan, Liu, Daren, Lopez, Alexander, Manoochehri, Kia, Marchini, Jonathan, Marcketta, Anthony, Maxwell, Evan K, McCarthy, Shane, Mitnaul, Lyndon J, O'Dushlaine, Colm, Overton, John D, Padilla, Maria Sotiropoulos, Paulding, Charles, Penn, John, Pradhan, Manasi, Reid, Jeffrey G, Schleicher, Thomas D, Schurmann, Claudia, Shuldiner, Alan, Staples, Jeffrey C, Sun, Dylan, Toledo, Karina, Ulloa, Ricardo H, Widom, Louis, Wolf, Sarah E, Yadav, Ashish, Ye, Bin, Ctr, Regeneron Genetics, Shah, Sonia [0000-0001-5860-4526], Henry, Albert [0000-0001-7422-2288], Roselli, Carolina [0000-0001-5267-6756], Lin, Honghuang [0000-0003-3043-3942], Chaffin, Mark D. [0000-0002-1234-5562], Helgadottir, Anna [0000-0002-1806-2467], Verweij, Niek [0000-0002-4303-7685], Almgren, Peter [0000-0002-0473-0241], Chen, Xu [0000-0002-7299-3238], Ghanbari, Mohsen [0000-0002-9476-7143], Giedraitis, Vilmantas [0000-0003-3423-2021], Gross, Stefan [0000-0003-4121-7161], Guðbjartsson, Daníel F. [0000-0002-5222-9857], Hyde, Craig L. [0000-0002-6939-287X], Ingelsson, Erik [0000-0003-2256-6972], Jukema, J. Wouter [0000-0002-3246-8359], Kleber, Marcus E. [0000-0003-0663-7275], Koekemoer, Andrea [0000-0001-8222-3547], Langenberg, Claudia [0000-0002-5017-7344], Lindgren, Cecilia M. [0000-0002-4903-9374], Lovering, Ruth C. [0000-0002-9791-0064], Luan, Jian’an [0000-0003-3137-6337], Magnusson, Patrik [0000-0002-7315-7899], Mahajan, Anubha [0000-0001-5585-3420], Mordi, Ify R. [0000-0002-2686-729X], Morris, Andrew D. [0000-0002-1766-0473], Nagle, Michael W. [0000-0002-4677-7582], Nelson, Christopher P. [0000-0001-8025-2897], Palmer, Colin N. A. [0000-0002-6415-6560], Rice, Kenneth M. [0000-0002-3071-7278], Rotter, Jerome I. [0000-0001-7191-1723], Salomaa, Veikko [0000-0001-7563-5324], van Setten, Jessica [0000-0002-4934-7510], Svensson, Per [0000-0003-0372-6272], Taylor, Kent D. [0000-0002-2756-4370], Teder-Laving, Maris [0000-0002-5872-1850], Teumer, Alexander [0000-0002-8309-094X], Tyl, Benoit [0000-0001-5297-8412], Uitterlinden, Andre G. [0000-0002-7276-3387], Völker, Uwe [0000-0002-5689-3448], Wiggins, Kerri L. [0000-0003-2749-1279], Hemingway, Harry [0000-0003-2279-0624], Yang, Jian [0000-0003-2001-2474], Visscher, Peter M. [0000-0002-2143-8760], Lubitz, Steven A. [0000-0002-9599-4866], Sattar, Naveed [0000-0002-1604-2593], Cappola, Thomas P. [0000-0002-9630-7204], Asselbergs, Folkert W. [0000-0002-1692-8669], Kuchenbaecker, Karoline [0000-0001-9726-603X], Ellinor, Patrick T. [0000-0002-2067-0533], Vasan, Ramachandran S. [0000-0001-7357-5970], Lumbers, R. Thomas [0000-0002-9077-4741], Apollo - University of Cambridge Repository, Chaffin, Mark D [0000-0002-1234-5562], Guðbjartsson, Daníel F [0000-0002-5222-9857], Hyde, Craig L [0000-0002-6939-287X], Jukema, J Wouter [0000-0002-3246-8359], Kleber, Marcus E [0000-0003-0663-7275], Lindgren, Cecilia M [0000-0002-4903-9374], Lovering, Ruth C [0000-0002-9791-0064], Luan, Jian'an [0000-0003-3137-6337], Mordi, Ify R [0000-0002-2686-729X], Morris, Andrew D [0000-0002-1766-0473], Nagle, Michael W [0000-0002-4677-7582], Nelson, Christopher P [0000-0001-8025-2897], Palmer, Colin NA [0000-0002-6415-6560], Rice, Kenneth M [0000-0002-3071-7278], Rotter, Jerome I [0000-0001-7191-1723], Taylor, Kent D [0000-0002-2756-4370], Uitterlinden, Andre G [0000-0002-7276-3387], Wiggins, Kerri L [0000-0003-2749-1279], Visscher, Peter M [0000-0002-2143-8760], Lubitz, Steven A [0000-0002-9599-4866], Cappola, Thomas P [0000-0002-9630-7204], Asselbergs, Folkert W [0000-0002-1692-8669], Ellinor, Patrick T [0000-0002-2067-0533], Vasan, Ramachandran S [0000-0001-7357-5970], Lumbers, R Thomas [0000-0002-9077-4741], Palmer, Colin N A [0000-0002-6415-6560], Cardiovascular Centre (CVC), University of Queensland [Brisbane], University College of London [London] (UCL), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], University Medical Center Groningen [Groningen] (UMCG), Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Framingham Heart Study, National Heart, Lung, and Blood Institute [Bethesda] (NHLBI)-Boston University [Boston] (BU), deCODE genetics [Reykjavik], Karolinska Institutet [Stockholm], Pfizer, University of Pennsylvania [Philadelphia], University of Groningen [Groningen], Imperial College London, Lund University [Lund], Herlev and Gentofte Hospital, Massachusetts General Hospital [Boston], Department of Neurobiology, Care Sciences and Society [Stockholm, Sweden] (Division of Family Medicine), Dalarna University, Regeneron Genetics Center, 777 Old Saw Mill River Road, Tarrytown, Department of Biostatistics, University of Washington [Seattle], Emory University School of Medicine, Emory University [Atlanta, GA], The University of Texas Medical School at Houston, Department of Molecular and Functional Genomics, Geisinger, Danville, PA, Brigham and Women's Hospital [Boston], Harvard Medical School [Boston] (HMS), Regeneron Genetics Center, 777 Old Saw Mill River Road, Tarrytown, NY, Novartis Institutes for BioMedical Research (NIBR), University of Liverpool, Universität Heidelberg [Heidelberg], Medizinische Fakultät Mannheim, The Alan Turing Institute, Ninewells Hospital and Medical School [Dundee], Universität Greifswald - University of Greifswald, German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), University of Minnesota System, Regeneron Pharmaceuticals [Tarrytown], Department of Clinical Sciences, Cardiovascular Epidemiology, Skane University Hospital [Lund], Institute of Genomics [Tartu, Estonia], University of Tartu, Robertson Centre for Biostatistics, University of Glasgow, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Uppsala University, Brigham & Women’s Hospital [Boston] (BWH), University of Maryland School of Medicine, University of Maryland System, School of Science and Engineering (Reykjavik University), Carver College of Medicine, University of Iowa, Geisinger Health System [Danville, PA, USA], Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, Stanford School of Medicine [Stanford], Stanford Medicine, Stanford University-Stanford University, Stanford Cardiovascular Institute, Uppsala Universitet [Uppsala], Leiden University Medical Center (LUMC), Einthoven Laboratory for Experimental Vascular Medicine (ELEVM - LEIDEN), Department of Public Health and Primary Care, University of Cambridge [UK] (CAM), Rigshospitalet [Copenhagen], Copenhagen University Hospital, Glenfield Hospital, University Hospitals Leicester, MRC Epidemiology Unit, University of Cambridge [UK] (CAM)-Institute of Metabolic Science, Big Data Institute, University of Oxford [Oxford], University of Iowa [Iowa City], The Wellcome Trust Centre for Human Genetics [Oxford], Synlab Academy, Synlab Holding Deutschland GmbH, Mannheim, Medical University Graz, Skane University Hospital [Malmo], Vanderbilt University School of Medicine [Nashville], University of Edinburgh, Université médicale de Vienne, Autriche, National Institute for Health and Welfare [Helsinki], University of Turku, Birmingham Women's and Children's NHS Foundation Trust, Kaiser Permanente, Harbor UCLA Medical Center [Torrance, Ca.], Los Angeles Biomedical Research Institute (LA BioMed), University Medical Center [Utrecht], University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), Seattle Epidemiologic Research and Information Center [Seattle], Institute of Cardiovascular and Medical Sciences [Glasgow], University of Glasgow, Department of Cardiology, Södersjukhuset, Stockholm, Estonian Genome and Medicine, Landspitali National University Hospital of Iceland, University of Iceland [Reykjavik], Aalborg University [Denmark] (AAU), Institut de Recherches SERVIER (IRS), Interfaculty Institute for Genetics and Functional Genomics, Ernst-Moritz-Arndt-Universität Greifswald, GlaxoSmithKline, Glaxo Smith Kline, Northeastern Ohio Medical University (NEOMED), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, British Heart Foundation Glasgow Cardiovascular Research Centre (BHF GCRC), University of Glasgow-NHS Greater Glasgow and Clyde, Department of Cardiovascular Sciences [Leicester], University of Leicester, Queensland Brain Institute, Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, University of Dundee, National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, Atherosclerosis Risk in Communities Study (ARIC)The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts N01-HC-55015, N01-HC- 55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC55021, N01-HC-55022, R01HL087641, R01HL59367, R01HL086694 and RC2 HL102419, National Human Genome Research Institute contract U01HG004402, and National Institutes of Health contract HHSN268200625226C. The authors thank the staff and participants of the ARIC study for their important contributions. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research. A systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT- CHF)This project was funded by a grant from the European Commission (FP7‐242209‐ BIOSTAT‐CHF, EudraCT 2010–020808–29). Cardiovascular Health Study (CHS) This CHS research was supported by NHLBI contracts HHSN268201200036C, HHSN268200800007C, HHSN268201800001C, HHSN268200960009C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, and NHLBI grants U01HL080295, R01HL087652, R01HL105756, R01HL103612, R01HL120393, and U01HL130114 with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided through R01AG023629 from the National Institute on Aging (NIA). A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org. The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences, CTSI grant UL1TR001881, and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) grant DK063491 to the Southern California Diabetes Endocrinology Research Center. deCODE Heart Failure Study (deCODE) We at deCODE thank the women and men of Iceland that have participated in our studies and our colleagues that contributed to data collection and processing. DiscovEHR We acknowledge and thank all participants in Geisinger’s MyCode Community Health Initiative for their support and permission to use their health and genomic information in the DiscovEHR collaboration. This work was supported by the Regeneron Genetics Center and Geisinger. Estonian Genome Center at the University of Tartu (EGCUT) This study was supported by Estonian Research Council Grant IUT20-60, EU, H2020 grant 692145, European Union through the European Regional Development Fund (Project No. 2014-2020.4.01.15-0012) GENTRANSMED. Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) The EPHESUS was supported by Pfizer, Inc. The European Prospective Investigation of Cancer, Norfolk study (EPIC-Norfolk) The EPIC-Norfolk Study is supported by programme grants from the Medical Research Council UK (G1000143) and Cancer Research UK (C864/A14136) and with additional support from the European Union, Stroke Association, British Heart Foundation, Research into Ageing, Department of Health, The Wellcome Trust and the Food Standards Agency. NJW and CL also acknowledge support from the Medical Research Council, UK (MC_UU_12015/1, MC_PC_13048). We thank all EPIC participants and staff for their contribution to the study, and thank staff from the Technical, Field Epidemiology and Data Functional Group Teams of the Medical Research Council Epidemiology Unit in Cambridge, UK, for carrying out sample preparation, DNA provision and quality control, genotyping and data handling work. Framingham Heart Study (FHS) This work was conducted using data and resources from the Framingham Heart Study (FHS) of the National Heart Lung and Blood Institute and Boston University School of Medicine. The study was supported by the National Heart, Lung and Blood Institute’s Framingham Heart Study (Contract No. N01-HC-25195 and HHSN268201500001I) and its contract with Affymetrix, Inc for genotyping services (Contract No.N02-HL-6-4278). The work was also supported by R01 HL093328, R01 HL105993, and R01 HL71039 (PI: Ramachandran). FINRISK V.S. has been supported by the Finnish Foundation for Cardiovascular Research. Genetics of Diabetes Audit and Research Tayside Scotland GoDARTS) The Wellcome Trust United Kingdom Type 2 Diabetes Case Control Collection (supporting GoDARTS) was funded by the Wellcome Trust (072960/Z/03/Z, 084726/Z/08/Z, 084727/Z/08/Z, 085475/Z/08/Z, 085475/B/08/Z) and as part of the EU IMI-SUMMIT programme. We acknowledge the support of the Health Informatics Centre, University of Dundee, for managing and supplying the anonymized data and NHS Tayside, the original data owner. The Genetic Risk Assessment of Defibrillator Events (GRADE) NIH-NHLBI R01 HL77398 (Genetic Modulators of Sudden Death). S.L. is supported by NIH grant 1R01HL139731 and American Heart Association 18SFRN34250007. The LUdwigshafen RIsk and Cardiovascular Health (LURIC) study We extend our appreciation to the participants of the LURIC study, without their collaboration, this article would not have been written. We thank the LURIC study team who were either temporarily or permanently involved in patient recruitment as well as sample and data handling, in addition to the laboratory staff at the Ludwigshafen General Hospital and the Universities of Freiburg and Ulm, Germany. LURIC has received funding from the 7th Framework Program (RiskyCAD, grant agreement number 305739 and Atheroremo, grant agreement number 201668) of the European Union. Malmö Diet and Cancer Study (MDCS) J. Gustav Smith was supported by grants from the Swedish Heart-Lung Foundation (2016- 0134 and 2016-0315), the Swedish Research Council (2017-02554), the European Research Council (ERC-STG-2015-679242), the Crafoord Foundation, Skåne University Hospital, the Scania county, governmental funding of clinical research within the Swedish National Health Service, a generous donation from the Knut and Alice Wallenberg foundation to the Wallenberg Center for Molecular Medicine in Lund, and funding from the Swedish Research Council (Linnaeus grant Dnr 349-2006-237, Strategic Research Area Exodiab Dnr 2009-1039) and Swedish Foundation for Strategic Research (Dnr IRC15- 0067) to the Lund University Diabetes Center. The Malmo Diet and Cancer Study was made possible by grants from the Swedish Cancer Society, the Swedish Medical Research Council, the Swedish Dairy Association, and the Malmo city council. Penn Heart Failure Study (PHFS) The study was supported by NIH grants (NIH R01L088577 and NIH R01H105993). Prevention of REnal and Vascular ENd-stage Disease (PREVEND) The Prevention of Renal and Vascular Endstage Disease Study (PREVEND) genetics is supported by the Dutch Kidney Foundation (Grant E033), the EU project grant GENECURE (FP-6 LSHM CT 2006 037697), the National Institutes of Health (grant LM010098), the Netherlands organisation for health research and development (NWO VENI grant 916.761.70), and the Dutch Inter University Cardiology Institute Netherlands (ICIN). Niek Verweij was supported by NWO VENI grant 016.186.125. PROspective Study of Pravastatin in the Elderly at Risk for vascular disease (PROSPER)The PROSPER study was supported by an investigator-initiated grant obtained from Bristol- Myers Squibb. Support for genotyping was provided by the seventh framework program of the European commission (grant 223004) and by the Netherlands Genomics Initiative (Netherlands Consortium for Healthy Aging grant 050-060-810). J.W.J. is an Established Clinical Investigator of the Netherlands Heart Foundation (grant 2001 D 032). Study of Health in Pomerania (SHIP) SHIP is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (grants no. 01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural Affairs as well as the Social Ministry of the Federal State of Mecklenburg-West Pomerania, and the network ‘Greifswald Approach to Individualized Medicine (GANI_MED)’ funded by the Federal Ministry of Education and Research (grant 03IS2061A). Genome-wide data have been supported by the Federal Ministry of Education and Research (grant no. 03ZIK012) and a joint grant from Siemens Healthineers, Erlangen, Germany and the Federal State of Mecklenburg- West Pomerania. The University of Greifswald is a member of the Caché Campus program of the InterSystems GmbH. Stabilization of Plaque using Darapladib-Thrombolysis in Myocardial Infarction 52 (SOLID)SOLID-TIMI 52 was funded by GlaxoSmithKline. TwinGene (TwinGene) TwinGene received funding from the Swedish Research Council (M-2005-1112), GenomEUtwin (EU/QLRT-2001-01254, QLG2-CT-2002-01254), NIH DK U01-066134, The Swedish Foundation for Strategic Research (SSF) and the Heart and Lung foundation no. 20070481. TwinGene is part of the Swedish Twin Registry which is managed by Karolinska Institutet and receives funding through the Swedish Research Council (2017–00641). UK Biobank (UKBiobank) This research has been conducted using the UK Biobank Resource under Application Number 15422. This work was supported in part by grants to R.T.L. from the EU/EFPIA Innovative Medicines Initiative 2 Joint Undertaking BigData@Heart grant no. 116074, MRC Proximity to Discovery Award Scheme, the American Heart Association Institute for Precision Mecidine, Pfizer Ltd, the University College London British Heart Foundation Research Accelerator (AA/18/6/34223), and was supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. A. H. is supported by the British Heart Foundation Cardiovascular Biomedicine PhD studentship. R.T.L is supported by a UK Research and Innovation Rutherford Fellowship and was previously supported by a National Institutes of Health Research Clinical Lectureship. Uppsala Longitudinal Study of Adult Men (ULSAM) J.Ä. is supported by the Swedish Research Council and the Swedish Heart Lung foundation. C.M.L is supported by the Li Ka Shing Foundation, WT-SSI/John Fell funds and by the NIHR Biomedical Research Centre, Oxford, by Widenlife and NIH (5P50HD028138- 27). Women’s Genome Health Study (WGHS) The WGHS is supported by the National Heart, Lung, and Blood Institute (HL043851 and HL080467, HL099355) and the National Cancer Institute (CA047988 and UM1CA182913), with collaborative scientific support and funding for genotyping provided by Amgen., Epidemiology, Internal Medicine, Læknadeild (HÍ), Faculty of Medicine (UI), Verkfræði- og náttúruvísindasvið (HÍ), School of Engineering and Natural Sciences (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, and University of Iceland
Subjects: 0301 basic medicine, Dánartíðni, Epidemiology, LOCI, 45/43, General Physics and Astronomy, Muscle Proteins, Genome-wide association study, Disease, Coronary Artery Disease, 030204 cardiovascular system & hematology, Bioinformatics, Genome-wide association studies, DISEASE, Ventricular Function, Left, Coronary artery disease, 0302 clinical medicine, Risk Factors, Atrial Fibrillation, IMPUTATION, Medicine, Blóðrásarsjúkdómar, 692/308/174, lcsh:Science, 2. Zero hunger, RISK, Multidisciplinary, Microfilament Proteins, article, Atrial fibrillation, Mendelian Randomization Analysis, CATALOG, 3. Good health, OBESITY, Erfðarannsóknir, Cardiomyopathies, Medical Genetics, Cyclin-Dependent Kinase Inhibitor p21, Science, 631/208/205/2138, Heart failure, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 631/443/592/2727, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, RESOURCE, Humans, Mortality, METAANALYSIS, Genetic association, Medicinsk genetik, Adaptor Proteins, Signal Transducing, Heart Failure, HYPERTENSION, business.industry, Case-control study, Klinisk medicin, 692/699/75/230, General Chemistry, Cardiovascular genetics, medicine.disease, R1, 030104 developmental biology, Case-Control Studies, lcsh:Q, Morbidity, Clinical Medicine, business, Apoptosis Regulatory Proteins, Carrier Proteins, Genome-Wide Association Study
Abstract: Publisher's version (útgefin grein), Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies., We acknowledge the contribution from the EchoGen Consortium.
Published: 2020

19. Physical activity and risks of breast and colorectal cancer : a Mendelian randomisation analysis

Author: Michael O. Woods, Fränzel J.B. van Duijnhoven, Tilman Kühn, Graham G. Giles, Temitope O. Keku, Konstantinos K. Tsilidis, Andrew T. Chan, Mingyang Song, Michael Hoffmeister, Gad Rennert, Tabitha A. Harrison, Anna H. Wu, Kenneth Offit, Mark A. Jenkins, Elizabeth A Platz, Sabina Sieri, Noralane M Lindor, John D. Potter, D Timothy Bishop, Barbara L. Banbury, Anne M. May, Sonja I. Berndt, José María Huerta, Antonia Trichopoulou, Paul D.P. Pharoah, Niki Dimou, Christopher I. Li, Roger L. Milne, Marc J. Gunter, Hermann Brenner, Martha L. Slattery, Catherine M. Tangen, Gianluca Severi, Richard M. Martin, Nabila Kazmi, Ruth C. Travis, Sanford D. Markowitz, Jeroen R. Huyghe, Heather Hampel, Ulrike Peters, John L. Hopper, Brigid M. Lynch, Krasimira Aleksandrova, Alicja Wolk, Merete Ellingjord-Dale, Li Li, Bethany Van Guelpen, Sergi Castellví-Bel, Edward Giovannucci, Steven J Gallinger, Annika Lindblom, Cornelia M. Ulrich, Stephen B. Gruber, Stephanie L. Schmit, Jenny Chang-Claude, Lorena Moreno, Victor Moreno, Nikos Papadimitriou, Stephen N. Thibodeau, Elio Riboli, Sophia Harlid, Polly A. Newcomb, Pavel Vodicka, Demetrius Albanes, Bas Bueno-de-Mesquita, Maria J. Sánchez, Sarah J Lewis, Timothy Robinson, Daniel D Buchanan, Loic Le Marchand, Carlo La Vecchia, Robert E Schoen, Neil Murphy, Giovanna Masala, Evelyn M. Monninkhof, Jane C. Figueiredo, Andrea Gsur, Jochen Hampe, Vittorio Perduca, Li Hsu, Emily White, Peter T. Campbell, School of Public Health - Department of Epidemiology and Biostatistics, Imperial College London, University of Bristol [Bristol], National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Department of Epidemiology, German Institute of Human Nutrition, Division of Cancer Epidemiology and Genetics [Bethesda, MD, États-Unis], National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Division of Clinical Epidemiology and Aging Research, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment [Bilthoven] (RIVM), The Cancer, Ageing and Somatic Mutation Programme [Cambridgeshire, UK], The Wellcome Trust Sanger Institute [Cambridge], Division of Cancer Epidemiology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital [Toronto, Canada] (MSH), University of Melbourne, Harvard School of Public Health, Department of Internal Medicine, Epidemiology, Human Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Medical Department 1 [Dresden, Germany], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Ohio State University [Columbus] (OSU), FESTO, Universität Stuttgart [Stuttgart], Centre for MEGA Epidemiology, The University of Melbourne, Victoria, Australia, CIBER de Epidemiología y Salud Pública (CIBERESP), Department of Medical Genetics, HMNC Brain Health, Department of Clinical Sciences and Community Health [Milan, Italy], Università degli Studi di Milano [Milano] (UNIMI), University of Hawai‘i [Mānoa] (UHM), Chinese Center for Disease Control and Prevention, Department of Clinical Genetics, Karolinska University Hospital [Stockholm], Mayo Clinic, Case Western Reserve University [Cleveland], Cancer Risk Factors and LifeStyle Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Julius Center for Health Sciences and Primary Care, University Medical Center [Utrecht], Cancer Epidemiology Centre, Cancer Council Victoria, Biomedical Research Centre Network for Rare Diseases, CIBER de Enfermedades Raras (CIBERER), Memorial Sloane Kettering Cancer Center [New York], Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Université Paris Descartes - Paris 5 (UPD5)-Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS), Department of Oncology, University of Cambridge [UK] (CAM), Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), Department of Community Medicine and Epidemiology, CHS National Cancer Control Center, School of Public Health [London, UK] (Faculty of Medicine), Andalusian School of Public Health [Granada], Istituto Nazionale dei Tumori, Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Mayo Clinic [Rochester], University of Oxford [Oxford], WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Dept of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School [Athens]-University of Athens Medical School [Athens], Helmholtz Centre for Ocean Research [Kiel] (GEOMAR), Department of Medical Biosciences and Pathology, Umeå University, Institute of Experimental Medicine, Czech Academy of Sciences [Prague] (CAS), Karolinska Institutet [Stockholm], Nutrition and Metabolism Section, International Agency for Research on Cancer, [Papadimitriou,N, Dimou,N, Gunter,MJ, Murphy,N] Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France. [Tsilidis,KK] Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece. [Tsilidis,KK, Ellingjord-Dale,M, Riboli,E] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Banbury,B, Harrison,TA, Hsu,L, Huyghe,JR, Li,CI, Newcomb,PA, Potter,JD, White,E, Peters,U] Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. [Martin,RM, Kazmi,N] MRC Integrative Epidemiology Unit (IEU), Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. [Martin,RM, Lewis,SJ, Robinson,TM] Bristol Medical School, Department of Population Health Sciences, University of Bristol, Bristol, UK. [Martin,RM] National Institute for Health Research (NIHR) Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and the University of Bristol, Bristol, UK. [Albanes,D, Berndt,SI] Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MA, USA. [Aleksandrova,K] German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany. [Bishop,DT] Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK. [Brenner,H, Hoffmeister,M] Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Brenner,H] Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany. [Brenner,H] German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. [Buchanan,DD, Giles,GG, Hopper,JL, Jenkins,MA, Lynch,B, Milne,R] Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia. [Buchanan,DD] Colorectal Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, VIC, Australia. [Buchanan,DD] Genetic Medicine and Family Cancer Clinic, The Royal Melbourne Hospital, Parkville, VIC, Australia [Bueno-de-Mesquita,B] Former senior scientist, Dept. for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), BA Bilthoven, Netherlands. [Bueno-de-Mesquita,B] Former associate professor, Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, Netherlands. [Bueno-de-Mesquita,B] ormer visiting professor, Dept. of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, St Mary’s Campus, Norfolk Place, London, London, UK. [Bueno-de-Mesquita,B] Former academic Icon / visiting professor, Dept. of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Pantai Valley, Kuala Lumpur, Malaysia. [Campbell,PT] Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, GA, USA. [Castellví-Bel,S, Moreno,L] Gastroenterology Department, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain. [Chan,AT, Song,M] Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. [Chan,AT, Song,M] Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. [Chang-Claude,J, Kühn,T] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Chang-Claude,J] University Medical Centre Hamburg-Eppendorf, University Cancer Centre Hamburg (UCCH), Hamburg, Germany. [Figueiredo,JC] Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. [Figueiredo,JC] Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. [Gallinger,SJ] Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada. [Giles,GG, Milne,R] Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, VIC, Australia. [Giovannucci,E, Song,M] Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA. [Giovannucci,E, Song,M] Department of Nutrition, T.H. H, Chan School of Public Health, Boston, MA, USA. [Giovannucci,E] Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA. [Gruber,SB, Schmit,SL] Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. [Gsur,A] Institute of Cancer Research, Department of Medicine I, Medical University Vienna, Vienna, Austria. [Hampe,J] Department of Medicine I, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden, Germany. [Hampel,H] Division of Human Genetics, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA. [Harlid,S] Department of Radiation Sciences, Oncology, Umea University, Umea, Sweden. [Hopper,JL] Department of Epidemiology, School of Public Health and Institute of Health and Environment, Seoul National University, Seoul, South Korea. [Hsu,L] Department of Biostatistics, University of Washington, Seattle, WA, USA. [Huerta,JM, Moreno,V, Sánchez,MJ] CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Huerta,JM] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Keku,TO] Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA. [La Vecchia,C, Trichopoulou,A] Hellenic Health Foundation, Athens, Greece. [La Vecchia,C] Dept. of Clinical Sciences and Community Health, Università degli Studi di Milano, Milano, Italy. [Le Marchand,L] University of Hawaii Cancer Center, Honolulu, HI, USA. [Li,L] Department of Family Medicine, University of Virginia, Charlottesville, VA, USA. [Lindblom,A] Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden. [Lindblom,A] Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. [Lindor,NM] Department of Health Science Research, Mayo Clinic, Scottsdale, AZ, USA. [Lynch,B] Physical Activity Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia. [Markowitz,SD] Departments of Medicine and Genetics, Case Comprehensive Cancer Center, Case Western Reserve University, and University Hospitals of Cleveland, Cleveland, OH, USA. [Masala,G] Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network - ISPRO, Florence, Italy. [May,AM, Monninkhof,E] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, GA UTRECHT, Netherlands. [Milne,R] Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, VIC, Australia. [Moreno,V] Cancer Prevention and Control Program, Catalan Institute of Oncology-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain. [Moreno,V] Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain. [Newcomb,PA] School of Public Health, University of Washington, Seattle, WA, USA. [Offit,K] Clinical Genetics Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. [Offit,K] Department of Medicine, Weill Cornell Medical College, New York, NY, USA. [Perduca,V, Severi,G] CESP, Fac. de médecine - Univ. ParisSud, Fac. de médecine - UVSQ I, Université Paris-Saclay, Villejuif, France. [Perduca,V, Severi,G] Gustave Roussy, Villejuif, France. [Perduca,V] Laboratoire de Mathématiques Appliquées MAP5 (UMR CNRS 8145), Université Paris Descartes, Paris, France. [Pharoah,PDP] Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. [Platz,EA] Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. [Rennert,G] Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa, Israel. [Rennert,G] 7Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. [Rennert,G] Clalit National Cancer Control Center, Haifa, Israel. [Sánchez,MJ] Andalusian School of Public Health, Biomedical Research Institute ibs.GRANADA, University of Granada, Granada, Spain. [Schmit,SL] Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. [Schoen,RE] Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. [Sieri,S] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Slattery,ML] Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA. [Tangen,CM] SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. [Thibodeau,SN] Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. [Travis,RC] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. [Ulrich,CM] Huntsman Cancer Institute and Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA. [van Duijnhoven,FJB] Division of Human Nutrition, Wageningen University and Research, Wageningen, Netherlands. [Van Guelpen,B] Department of Radiation Sciences, Oncology Unit, Umeå University, Umeå, Sweden. [Van Guelpen,B] Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden. [Vodicka,P] Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic. [Vodicka,P] Faculty of Medicine and Biomedical Center in Pilsen, Charles University, Pilsen, Czech Republic. [Vodicka,P] Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic. [White,E, Peters,U] Department of Epidemiology, University of Washington, Seattle, WA, USA. [Wolk,A] Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. [Woods,MO] Memorial University of Newfoundland, Discipline of Genetics, St. John’s, Canada. [Wu,AH] University of Southern California, Preventative Medicine, Los Angeles, CA, USA., This work was supported by the National Cancer Institute, the International Agency for Research on Cancer and a Cancer Research UK program grant (C18281/A19169 to RMM, SJL & NK). RMM was supported by the National Institute for Health Research (NIHR) Bristol Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. The funding sources for BCAC, CCFR, GECCO, and CORECT consortia are presented in detail in the appendix in the Supplementary material., Tsilidis, Konstantinos K [0000-0002-8452-8472], Martin, Richard M [0000-0002-7992-7719], Lewis, Sarah J [0000-0003-4311-6890], Robinson, Timothy M [0000-0003-0933-646X], Timothy Bishop, D [0000-0002-8752-8785], Buchanan, Daniel D [0000-0003-2225-6675], Chan, Andrew T [0000-0001-7284-6767], Giles, Graham G [0000-0003-4946-9099], Gsur, Andrea [0000-0002-9795-1528], Hampe, Jochen [0000-0002-2421-6127], Hampel, Heather [0000-0001-7558-9794], Harlid, Sophia [0000-0001-8540-6891], Harrison, Tabitha A [0000-0002-4173-7530], María Huerta, José [0000-0002-9637-3869], Huyghe, Jeroen R [0000-0001-6027-9806], Jenkins, Mark A [0000-0002-8964-6160], La Vecchia, Carlo [0000-0003-1441-897X], Masala, Giovanna [0000-0002-5758-9069], Milne, Roger [0000-0001-5764-7268], Moreno, Victor [0000-0002-2818-5487], Newcomb, Polly A [0000-0001-8786-0043], Perduca, Vittorio [0000-0003-0339-0473], Pharoah, Paul D P [0000-0001-8494-732X], Potter, John D [0000-0001-5439-1500], Rennert, Gad [0000-0002-8512-068X], Riboli, Elio [0000-0001-6795-6080], Schmit, Stephanie L [0000-0001-5931-1194], Schoen, Robert E [0000-0001-7153-2766], Van Guelpen, Bethany [0000-0002-9692-101X], Wolk, Alicja [0000-0001-7387-6845], Peters, Ulrike [0000-0001-5666-9318], Murphy, Neil [0000-0003-3347-8249], Apollo - University of Cambridge Repository, Tsilidis, Konstantinos K. [0000-0002-8452-8472], Martin, Richard M. [0000-0002-7992-7719], Lewis, Sarah J. [0000-0003-4311-6890], Timothy Bishop, D. [0000-0002-8752-8785], Buchanan, Daniel D. [0000-0003-2225-6675], Chan, Andrew T. [0000-0001-7284-6767], Giles, Graham G. [0000-0003-4946-9099], Harrison, Tabitha A. [0000-0002-4173-7530], Huyghe, Jeroen R. [0000-0001-6027-9806], Jenkins, Mark A. [0000-0002-8964-6160], Newcomb, Polly A. [0000-0001-8786-0043], Pharoah, Paul D. P. [0000-0001-8494-732X], Potter, John D. [0000-0001-5439-1500], Schmit, Stephanie L. [0000-0001-5931-1194], Schoen, Robert E. [0000-0001-7153-2766], and Pharoah, Paul DP [0000-0001-8494-732X]
Subjects: Oncology, Epidemiology, Colorectal cancer, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Accelerometry [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Molecular Epidemiology::Mendelian Randomization Analysis [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Breast cancer, Epidemiology of cancer, Accelerometry, Odds Ratio, lcsh:Science, skin and connective tissue diseases, Cancer genetics, ComputingMilieux_MISCELLANEOUS, Cancer, 0303 health sciences, Biobank, 3. Good health, 030220 oncology & carcinogenesis, ICEP, Factores de riesgo, medicine.medical_specialty, Science, 631/67/2324, Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms::Colorectal Neoplasms, Hereditary Nonpolyposis [Medical Subject Headings], Breast Neoplasms/genetics, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Càncer colorectal, Anthropology, Education, Sociology and Social Phenomena::Human Activities::Exercise [Medical Subject Headings], Humans, Epidemiologia, Exercise, VLAG, Cancer och onkologi, 45, 631/67/1347, Odds ratio, Mendelian Randomization Analysis, medicine.disease, Colorectal Neoplasms/genetics, 030104 developmental biology, Analyses, Risk factors, Check Tags::Female [Medical Subject Headings], Cancer and Oncology, lcsh:Q, Breast neoplasms, 0301 basic medicine, 631/67/1504/1885, Nutrition and Disease, General Physics and Astronomy, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Risk Factors, Neoplasias colorrectales, Voeding en Ziekte, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Odds Ratio [Medical Subject Headings], Multidisciplinary, article, Public Health, Global Health, Social Medicine and Epidemiology, Polymorphism, Single Nucleotide/genetics, Ejercicio físico, Neoplasias de la mama, Female, Colorectal Neoplasms, 631/67, 141, Breast Neoplasms, 45/23, Polymorphism, Single Nucleotide, Colorectal neoplasms, Càncer de mama, Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Susceptibility::Genetic Predisposition to Disease [Medical Subject Headings], Cancer epidemiology, 631/67/68, Internal medicine, Mendelian randomization, medicine, Journal Article, Life Science, Genetic Predisposition to Disease, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], 030304 developmental biology, Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single Nucleotide [Medical Subject Headings], business.industry, General Chemistry, Physical fitness, Confidence interval, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Condició física
Abstract: Physical activity has been associated with lower risks of breast and colorectal cancer in epidemiological studies; however, it is unknown if these associations are causal or confounded. In two-sample Mendelian randomisation analyses, using summary genetic data from the UK Biobank and GWA consortia, we found that a one standard deviation increment in average acceleration was associated with lower risks of breast cancer (odds ratio [OR]: 0.51, 95% confidence interval [CI]: 0.27 to 0.98, P-value = 0.04) and colorectal cancer (OR: 0.66, 95% CI: 0.48 to 0.90, P-value = 0.01). We found similar magnitude inverse associations for estrogen positive (ER+ve) breast cancer and for colon cancer. Our results support a potentially causal relationship between higher physical activity levels and lower risks of breast cancer and colorectal cancer. Based on these data, the promotion of physical activity is probably an effective strategy in the primary prevention of these commonly diagnosed cancers., United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Cancer Institute (NCI), International Agency for Research on Cancer, Cancer Research UK C18281/A19169, National Institute for Health Research (NIHR)
Published: 2020

20. Associations of autozygosity with a broad range of human phenotypes

Author: Dennis O. Mook-Kanamori, Salma M. Wakil, Lisa R. Yanek, Dominique P.V. de Kleijn, Gert J. de Borst, Alison D. Murray, Kamran Guity, Vincent W. V. Jaddoe, Mario Pirastu, Carole Ober, Giuseppe Matullo, Charles N. Rotimi, Daniela Ruggiero, Teresa Tusié-Luna, Wolfgang Lieb, Chew-Kiat Heng, John R. B. Perry, Hortensia Moreno-Macías, Jie Zhou, John M. Starr, Juhani Junttila, Lei Yu, Danielle Posthuma, Marcus Dörr, Yingchang Lu, Jonathan P. Bradfield, Einat Granot-Hershkovitz, Karina Meidtner, Wouter van Rheenen, T Esko, Maris Alver, Wen-Jane Lee, Zhengming Chen, Jennifer A. Brody, Paolo Gasparini, Yii-Der Ida Chen, Cinzia Sala, Peter P. Pramstaller, Gauri Prasad, Nana Matoba, Natalie Terzikhan, Simonetta Guarrera, Bjarke Feenstra, Peter Vollenweider, Smeeta Shrestha, Yi-Jen Hung, Lilja Stefansdottir, David R. Weir, Felix R. Day, Antonietta Robino, Liang Zhang, Lluis Quintana-Murci, Nicholas J. Timpson, Robyn E Wootton, Xue W. Mei, Dharambir K. Sanghera, Gisli Masson, Debbie A Lawlor, Thomas Meitinger, Sharon L.R. Kardia, Peter K. Joshi, Frank J. A. van Rooij, Claude Bouchard, Cassandra N. Spracklen, Ken K. Ong, Taulant Muka, Guanjie Chen, Laura J. Scott, Walter Palmas, Daniel I. Chasman, Sarah E. Medland, Krista Fischer, Blair H. Smith, Jon K. Sigurdsson, Leon Straker, Clara Viberti, Yuan Shi, Louis Pérusse, Peter J. van der Most, Timo Tõnis Sikka, Chris Haley, Kuang Lin, Leif Groop, Hester M. den Ruijter, Hakon Hakonarson, Masato Akiyama, Stephan J. L. Bakker, Sonja I. Berndt, Jeffery R. O'Connell, Cisca Wijmenga, Daniele Cusi, Lorena Orozco, Kristjan H. S. Moore, Kevin Sandow, Stephen S. Rich, Stephanie J. Loomis, George Davey Smith, Cornelia M. van Duijn, Sharvari Rahul Shukla, Agnar Helgason, Thorsten Kessler, Anuj Goel, Dan Mason, David W. Clark, James S. Pankow, Simona Vaccargiu, Uwe Völker, Tamara B. Harris, Matthew A. Allison, Clicerio Gonzalez, Sarju Ralhan, I-Te Lee, Matthias Laudes, Yen-Feng Chiu, Neil Poulter, Benjamin Lehne, John Wright, Lawrence F. Bielak, Philip L. De Jager, Reinhold Schmidt, Ya Xing Wang, Matthias Nauck, Diana L. Cousminer, Patrick Deelen, Ani Manichaikul, Stephen J. Chanock, Anders Hamsten, Barry I. Freedman, Gudmar Thorleifsson, Peter Kraft, Ozren Polasek, Jie Yao, Yoshinori Murakami, Paul M. Ridker, Anubha Mahajan, Struan F.A. Grant, Claudia Schurmann, Bjarni Gunnarsson, Catriona L. K. Barnes, Jessica van Setten, Sandosh Padmanabhan, Alena Stančáková, Markus M. Lerch, Anuradha Jagadeesan, Franco Giulianini, Daniel F. Gudbjartsson, Dwaipayan Bharadwaj, Shengchao Alfred Li, Peter S. Sever, Trevor A. Mori, Albertine J. Oldehinkel, Koichi Matsuda, Xueling Sim, Evangelos Evangelou, André G. Uitterlinden, Pekka Jousilahti, Yukihide Momozawa, Ioanna Tzoulaki, Chao A. Hsiung, Ginevra Biino, Murielle Bochud, Hannele Mattsson, Ilja M. Nolte, Sarah H. Wild, Patricia B. Munroe, Jianjun Liu, Bruce M. Psaty, Giriraj R. Chandak, Masahiro Kanai, Tony R. Merriman, Teemu Palviainen, Rodney A. Lea, Janie Corley, Nicholas J. Wareham, Alan B. Zonderman, Makoto Hirata, Matthew J. Bixley, Caroline Hayward, Nora Franceschini, Kristel R van Eijk, Etienne Patin, Daniel Shriner, Niek Verweij, Xiuqing Guo, Fredrik Karpe, Ruth J. F. Loos, Tiinamaija Tuomi, Ashley van der Spek, Patricia A. Peyser, Jessica D. Faul, Christian Fuchsberger, David Cesarini, Alex S. F. Doney, Janine F. Felix, Cornelius A. Rietveld, Jagadish Vangipurapu, Tanguy Corre, Line Skotte, Rajkumar Dorajoo, Catherine Igartua, Meena Kumari, Nona Sotoodehnia, Leonard H. van den Berg, Najaf Amin, Dale R. Nyholt, Harry Campbell, Massimiliano Cocca, Scott D. Gordon, Patrik K. E. Magnusson, John C. Chambers, Traci M. Bartz, Mike A. Nalls, Tin Aung, Nduna Dzimiri, Colin N. A. Palmer, Rob M. van Dam, Johanna Kuusisto, Russell P. Tracy, Anna Damulina, Pierre-Emmanuel Morange, Sylvain Foisy, Jing Hua Zhao, Nicholas G. Martin, Ching-Yu Cheng, Mariaelisa Graff, Rashmi B. Prasad, Alice Stanton, David-Alexandre Trégouët, Yu Guo, Helen R. Warren, Lyn R. Griffiths, Weihua Meng, Annika Tillander, Christa Meisinger, Albert V. Smith, Mark I. McCarthy, Jingyun Yang, Marine Germain, Neil Small, Linda Broer, Vilmundur Gudnason, Gunnar K. Pálsson, Michele K. Evans, Alexander Teumer, Mark J. Caulfield, Giorgia Girotto, Thomas Lumley, Tinca J. C. Polderman, Wei Zhao, Carlos A. Aguilar-Salinas, Jari Lahti, Matthew L. Albert, Yechiel Friedlander, Veikko Salomaa, Iona Y Millwood, Jan H. Veldink, Archie Campbell, Andres Metspalu, Ulf Gyllensten, Grant W. Montgomery, Veronique Vitart, Jai Rup Singh, Saima Afaq, Alan R. Shuldiner, Miao-Li Chee, Adebowale Adeyemo, Jennifer A. Smith, David A. van Heel, Jaspal S. Kooner, Daniela Toniolo, Cristian Pattaro, Jerome I. Rotter, John Whitfield, Melissa C. Smart, Kari E. North, Salman M. Tajuddin, Tallapragada Divya Sri Priyanka, Christopher A. Haiman, Diane M. Becker, Bernhard K. Krämer, Paul Elliott, Lihua Wang, He Gao, Patrick Sulem, Jinyan Huang, Chiea Chuen Khor, Ruifang Li-Gao, Åsa Johansson, Winfried März, Shai Carmi, Ilaria Gandin, Eric Boerwinkle, Gardar Sveinbjornsson, Saskia P. Hagenaars, Sander W. van der Laan, Gerard Pasterkamp, E-Shyong Tai, Hagit Hochner, Yih Chung Tham, Kent D. Taylor, Kari Stefansson, Matt J. Neville, Craig E. Pennell, Yanchun Bao, Annelot M. Dekker, Helena Schmidt, Mehdi Hedayati, Joshua Elliott, Ian J. Deary, Iris E. Jansen, Judith B. Borja, Edith Hofer, Martin Gögele, Igor Rudan, Lude Franke, Matthias Munz, Folkert W. Asselbergs, Bengt Sennblad, Imo Hofer, John D. Rioux, Pim van der Harst, Bahareh Sedaghati-khayat, Giovanni Cugliari, Morris A. Swertz, Francine Grodstein, Erwin P. Bottinger, Carol A. Wang, Andre Franke, Brian F. Meyer, Adele M. Taylor, Klodian Dhana, Jian'an Luan, Constance Turman, Robert A. Scott, May E. Montasser, Alison Pattie, Marco Brumat, Liming Li, Heiner Boeing, Karen L. Mohlke, Clemens Baumbach, Bishwa Raj Sapkota, Unnur Thorsteinsdottir, Naveed Sattar, Amy R. Bentley, Matthias B. Schulze, Ivana Kolcic, Stella Trompet, Sarah E. Harris, Ayo P. Doumatey, Charumathi Sabanayagam, David Eccles, Mary F. Feitosa, Jost B. Jonas, Massimo Mezzavilla, Mark O. Goodarzi, David Ellinghaus, Heribert Schunkert, Christian Gieger, Heikki V. Huikuri, Lingyao Zeng, Johan G. Eriksson, Woon-Puay Koh, Yucheng Jia, Gurpreet Singh Wander, James F. Wilson, Torgny Karlsson, Steven C. Hunt, Weihua Zhang, Maria Pina Concas, Zoltán Kutalik, Rebecca Rohde, Chittaranjan S. Yajnik, Yasaman Saba, Dabeeru C. Rao, Robin G. Walters, Reedik Mägi, Marie Loh, Eero Vuoksimaa, Josyf C. Mychaleckyj, Katri Räikkönen, Philippe Goyette, M. Arfan Ikram, Alicia Huerta-Chagoya, David J. Porteous, Teresa Nutile, J. Wouter Jukema, Noha A. Yousri, Yoichiro Kamatani, Maryam S. Daneshpour, Babette S. Zemel, Rona J. Strawbridge, Tien Yin Wong, Claudia Langenberg, Amy Moore, Marcus E. Kleber, Fereidoun Azizi, Avner Halevy, Erika Salvi, Francis S. Collins, Markku Laakso, Tim Kacprowski, S. Sunna Ebenesersdóttir, William R. Scott, Michael Boehnke, Jin-Fang Chai, Markus Perola, Nicola Pirastu, Wayne Huey-Herng Sheu, Robert Karlsson, Lenore J. Launer, Lili Milani, Renée de Mutsert, Fernando Rivadeneira, David A. Bennett, Nicola D. Kerrison, Paolo Manunta, Graciela E. Delgado, Magnus Johannesson, Carolina Medina-Gomez, Alanna C. Morrison, Kay-Tee Khaw, Jian-Min Yuan, Jaakko Kaprio, Melanie Waldenberger, Ralf Ewert, Hugoline G. de Haan, Andrew A. Hicks, Yukinori Okada, Maria Sabater-Lleal, Marilyn C. Cornelis, Stephanie J. London, Federica Rizzi, Jeanette Erdmann, Marina Ciullo, Michiaki Kubo, University of Edinburgh, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Osaka University Graduate School of Medicine, Laboratory for Cardiovascular Genomics and Informatics [Yokohama] (RIKEN IMS), RIKEN Center for Integrative Medical Sciences [Yokohama] (RIKEN IMS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN)-RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), deCODE genetics [Reykjavik], Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK (BIHR), Area Science Park, Università degli studi di Trieste = University of Trieste, MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Interfaculty Institute for Genetics and Functional Genomics, Universität Greifswald - University of Greifswald, Harbor UCLA Medical Center [Torrance, Ca.], Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, Department of Electrical and Computer Engineering [Waterloo] (ECE), University of Waterloo [Waterloo], Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Institute of Pop. Genetics, CNR, Sassari, Shardna life science Pula Cagliari, Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne = University of Lausanne (UNIL), Medstar Research Institute, Florida State University [Tallahassee] (FSU), University Medical Center [Utrecht], Centre for Population Health Sciences, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), California State University [Sacramento], Department of Thrombosis and Haemostasis, Leiden University Medical Center (LUMC), Universiteit Leiden-Universiteit Leiden, Medical University Graz, Department of Neurology, Alzheimer Centre, VU Medical Centre, Amsterdam, Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty of Mannheim, University of Heidelberg, Heidelberg, Frederick National Laboratory for Cancer Research (FNLCR), Wellcome Trust Centre of Human Genetics, University of Oxford, Department of Epidemiology, German Institute of Human Nutrition, University Medical Center Groningen [Groningen] (UMCG), Institute of Genetics and Biophysics, National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), Department of Medicine, Surgery, and Dentistry, University of Milano, Icelandic Heart Association, Kopavogur, Iceland., Department of Epidemiology [Rotterdam], Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Glasgow, Department of Cardiology, Leiden University Medical Center, Leiden, Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, Queen Mary University of London (QMUL), General Internal Medicine, Johns Hopkins School of Medicine, Johns Hopkins University School of Medicine [Baltimore], Institut de biologie moléculaire des plantes (IBMP), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Immunobiologie des Cellules dendritiques, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Translationnelle - Center for Translational Science (CRT), Institut Pasteur [Paris] (IP), Genentech, Inc., Genentech, Inc. [San Francisco], University of Tartu, Duke-NUS Medical School [Singapore], Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke (DifE), Leibniz Association, Human Genome Sequencing Center, Baylor College of Medicine, Baylor College of Medicine (BCM), Baylor University-Baylor University, University of San Carlos, Office of Population Studies Foundation, Icahn School of Medicine at Mount Sinai [New York] (MSSM), King‘s College London, Division of Cancer Epidemiology and Genetics, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), University of Oxford, Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty of Mannheim, University of Heidelberg, Division of Molecular & Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, Department of Internal Medicine B, University Medicine Greifswald, Greifswald, University of Chicago, University of Huddersfield, Infectious diseases division, Department of internal medicine, Washington University in Saint Louis (WUSTL), Section on Nephrology [Winston-Salem, NC, USA] (Department of Internal Medicine), Wake Forest School of Medicine [Winston-Salem], Wake Forest Baptist Medical Center-Wake Forest Baptist Medical Center, Radcliffe Department of Medicine [Oxford], Harvard School of Public Health, Kunming University of Science and Technology (KMUST), Sans affiliation, University of Southern California (USC), National Institute on Aging [Bethesda, USA] (NIA), National Institutes of Health [Bethesda] (NIH), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), MRC Centrer for Nutritional Epidemiology and Cancer Prevention and Survival, University of Cambridge [UK] (CAM), National University of Singapore (NUS), Experimental Cardiology Laboratory (ECL), Unirversity Medical Center, Department of Medical Statistics, Epidemiology and Medical Informatics, University of Zagreb, Department of Medical Genetics, Department of Medicine, University of Eastern Finland-Kuopio University Hospital, MRC Epidemiology Unit, University of Cambridge [UK] (CAM)-Institute of Metabolic Science, Capital Normal University [Beijing], Saw Swee Hock School of Public Health, National Institute for Environmental Health Sciences Research Triangle Park, Brown University, MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, Toyota Research Institute, Helmholtz Zentrum München = German Research Center for Environmental Health, Department of Chemistry and Biochemistry [Boulder], University of Colorado [Boulder], Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital de la Timone [CHU - APHM] (TIMONE), Metacohorts Consortium, Universiteit Leiden, Institute of Clinical Chemistry and Laboratory Medicine, University of Groningen [Groningen], Medical Research Concil Epidemiology Unit, Institute of Medical Science, Faculty of Medicine, Genetics and Pathology, Imperial College London, Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Brigham and Women's Hospital [Boston], Erasmus University Rotterdam, Department of Chronic Disease Prevention, National Institute for Health and Welfare [Helsinki], Department of Biostatistics and Center for Statistical Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU), Stockholm Bioinformatics Center (SBC), Stockholm University, Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, University of Utrecht, Utrecht, INRH, Department of Genetics, Los Angeles Biomedical Research Institute (LA BioMed), Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán - National Institute of Medical Science and Nutrition Salvador Zubiran [Mexico], Western General Hospital, German Research Center for Environmental Health - Helmholtz Center München (GmbH), Medical Research Council, Division of Cancer Control and Population Sciences, University of Pittsburgh Cancer Institute-University of Pittsburgh Graduate School of Public Health, Zhengzhou University of Light Industry, Department of Electrical and Electronic Engineering [Niigata Univ.], Niigata University, Genetic Epidemiology Unit, University College of London [London] (UCL), Aston Business School, Aston University [Birmingham], Division of Cancer Epidemiology and Genetics [Bethesda, MD, États-Unis], Centre Hospitalier Universitaire Vaudois (CHUV), Pennington Biomedical Research Center, University of Washington [Seattle], Guy's and St Thomas' Hospitals, Northwestern Polytechnical University [Xi'an] (NPU), Department of Social Medicine, University of Bristol [Bristol], Department of Genomics of Common Disease [London, UK], Imperial College London-Hammersmith Hospital NHS Imperial College Healthcare, Department of Internal Medicine, Institute of Clinical Molecular Biology, Kiel University, Medizinische Klinik II, Universität zu Lübeck = University of Lübeck [Lübeck], Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina, Institute for Social Research, University of Michigan System-University of Michigan System, Division of Statistical Genomics, Washington University School of Medicine, Institute for Clinical Molecular Biology, Christian-Albrechts-Universität zu Kiel (CAU), Department of Physics, RISSC-Lab-University of Naples Federico II = Università degli studi di Napoli Federico II, Lund University [Lund], Icelandic Heart Association, Heart Preventive Clinic and Research Institute, The Center for Applied Genomics, Children’s Hospital of Philadelphia (CHOP ), Génétique moléculaire de la neurotransmission et des processus neurodégénératifs (LGMNPN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Medical Research Center Oulu, University of Oulu, University of Utah School of Medicine [Salt Lake City], The Generation R Study, Pediatrics, Epidemiology, Center for Translational and Computational Neuroimmunology [New York, NY, États-Unis] (CTCN), Department of Neurology [New York, NY, États-Unis], Columbia University Medical Center (CUMC), Columbia University [New York]-Columbia University [New York]-Columbia University Medical Center (CUMC), Columbia University [New York]-Columbia University [New York], Universität Heidelberg [Heidelberg] = Heidelberg University, Interuniversity Cardiology Institute Netherlands, School of Public Health, University of Michigan [Dearborn], Department of Epidemiology and Public Health, University of Kuopio, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Institute of Epidemiology and Biobank PopGen, Department of Biostatistics, University of Washington, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Clinical Institute of Medical and Chemical Laboratory Diagnostics, Karl-Franzens-Universität Graz, Department of Genetics, Biology and Biochemistry, Università degli studi di Torino = University of Turin (UNITO), Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), QIMR Berghofer Medical Research Institute, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC)-UNC Gillings School of Global Public Health-Carolina Center for Genome Sciences, University of Illinois [Chicago] (UIC), University of Illinois System, Experimental Cardiology Laboratory, Genetic Epidemiology and Clinical Research Group, Umea University Hospital, Functional Genomics, Erasmus Medical Centre, National Human Genome Research Institute (NHGRI), School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), Department of Pathological Biochemistry, Royal Infirmary, German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Institute of Metabolic Science, MRC, University of Maryland School of Medicine [Baltimore, MD, USA], Centre for Molecular Epidemiology, Centre for Causal Analyses in Translational Epidemiology, University of Bristol [Bristol]-Medical Research Council, IRCCS San Raffaele Scientific Institute [Milan, Italie], U937, Génomique cardiovasculaire, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), University of Michigan System, HMNC Brain Health, Singapore Eye Research Institute, Partenaires INRAE, Institut d'Électronique et des Technologies du numéRique (IETR), Université de Nantes (UN)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Institute for Molecular Medicine Finland [Helsinki] (FIMM), Helsinki Institute of Life Science (HiLIFE), Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Department of Psychiatry and Psychotherapy, Rheinische Friedrich-Wilhelms-Universität Bonn, University of Groningen, Department of Genomics of Common Disease, Department of Microbiology, The Freeman Hospital, Department Biostatistics University of North Carolina, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, Clark, D. W., Okada, Y., Moore, K. H. S., Mason, D., Pirastu, N., Gandin, I., Mattsson, H., Barnes, C. L. K., Lin, K., Zhao, J. H., Deelen, P., Rohde, R., Schurmann, C., Guo, X., Giulianini, F., Zhang, W., Medina-Gomez, C., Karlsson, R., Bao, Y., Bartz, T. M., Baumbach, C., Biino, G., Bixley, M. J., Brumat, M., Chai, J. -F., Corre, T., Cousminer, D. L., Dekker, A. M., Eccles, D. A., van Eijk, K. R., Fuchsberger, C., Gao, H., Germain, M., Gordon, S. D., de Haan, H. G., Harris, S. E., Hofer, E., Huerta-Chagoya, A., Igartua, C., Jansen, I. E., Jia, Y., Kacprowski, T., Karlsson, T., Kleber, M. E., Li, S. A., Li-Gao, R., Mahajan, A., Matsuda, K., Meidtner, K., Meng, W., Montasser, M. E., van der Most, P. J., Munz, M., Nutile, T., Palviainen, T., Prasad, G., Prasad, R. B., Priyanka, T. D. S., Rizzi, F., Salvi, E., Sapkota, B. R., Shriner, D., Skotte, L., Smart, M. C., Smith, A. V., van der Spek, A., Spracklen, C. N., Strawbridge, R. J., Tajuddin, S. M., Trompet, S., Turman, C., Verweij, N., Viberti, C., Wang, L., Warren, H. R., Wootton, R. E., Yanek, L. R., Yao, J., Yousri, N. A., Zhao, W., Adeyemo, A. A., Afaq, S., Aguilar-Salinas, C. A., Akiyama, M., Albert, M. L., Allison, M. A., Alver, M., Aung, T., Azizi, F., Bentley, A. R., Boeing, H., Boerwinkle, E., Borja, J. B., de Borst, G. J., Bottinger, E. P., Broer, L., Campbell, H., Chanock, S., Chee, M. -L., Chen, G., Chen, Y. -D. I., Chen, Z., Chiu, Y. -F., Cocca, M., Collins, F. S., Concas, M. P., Corley, J., Cugliari, G., van Dam, R. M., Damulina, A., Daneshpour, M. S., Day, F. R., Delgado, G. E., Dhana, K., Doney, A. S. F., Dorr, M., Doumatey, A. P., Dzimiri, N., Ebenesersdottir, S. S., Elliott, J., Elliott, P., Ewert, R., Felix, J. F., Fischer, K., Freedman, B. I., Girotto, G., Goel, A., Gogele, M., Goodarzi, M. O., Graff, M., Granot-Hershkovitz, E., Grodstein, F., Guarrera, S., Gudbjartsson, D. F., Guity, K., Gunnarsson, B., Guo, Y., Hagenaars, S. P., Haiman, C. A., Halevy, A., Harris, T. B., Hedayati, M., van Heel, D. A., Hirata, M., Hofer, I., Hsiung, C. A., Huang, J., Hung, Y. -J., Ikram, M. A., Jagadeesan, A., Jousilahti, P., Kamatani, Y., Kanai, M., Kerrison, N. D., Kessler, T., Khaw, K. -T., Khor, C. C., de Kleijn, D. P. V., Koh, W. -P., Kolcic, I., Kraft, P., Kramer, B. K., Kutalik, Z., Kuusisto, J., Langenberg, C., Launer, L. J., Lawlor, D. A., Lee, I. -T., Lee, W. -J., Lerch, M. M., Li, L., Liu, J., Loh, M., London, S. J., Loomis, S., Lu, Y., Luan, J., Magi, R., Manichaikul, A. W., Manunta, P., Masson, G., Matoba, N., Mei, X. W., Meisinger, C., Meitinger, T., Mezzavilla, M., Milani, L., Millwood, I. Y., Momozawa, Y., Moore, A., Morange, P. -E., Moreno-Macias, H., Mori, T. A., Morrison, A. C., Muka, T., Murakami, Y., Murray, A. D., de Mutsert, R., Mychaleckyj, J. C., Nalls, M. A., Nauck, M., Neville, M. J., Nolte, I. M., Ong, K. K., Orozco, L., Padmanabhan, S., Palsson, G., Pankow, J. S., Pattaro, C., Pattie, A., Polasek, O., Poulter, N., Pramstaller, P. P., Quintana-Murci, L., Raikkonen, K., Ralhan, S., Rao, D. C., van Rheenen, W., Rich, S. S., Ridker, P. M., Rietveld, C. A., Robino, A., van Rooij, F. J. A., Ruggiero, D., Saba, Y., Sabanayagam, C., Sabater-Lleal, M., Sala, C. F., Salomaa, V., Sandow, K., Schmidt, H., Scott, L. J., Scott, W. R., Sedaghati-Khayat, B., Sennblad, B., van Setten, J., Sever, P. J., Sheu, W. H. -H., Shi, Y., Shrestha, S., Shukla, S. R., Sigurdsson, J. K., Sikka, T. T., Singh, J. R., Smith, B. H., Stancakova, A., Stanton, A., Starr, J. M., Stefansdottir, L., Straker, L., Sulem, P., Sveinbjornsson, G., Swertz, M. A., Taylor, A. M., Taylor, K. D., Terzikhan, N., Tham, Y. -C., Thorleifsson, G., Thorsteinsdottir, U., Tillander, A., Tracy, R. P., Tusie-Luna, T., Tzoulaki, I., Vaccargiu, S., Vangipurapu, J., Veldink, J. H., Vitart, V., Volker, U., Vuoksimaa, E., Wakil, S. M., Waldenberger, M., Wander, G. S., Wang, Y. X., Wareham, N. J., Wild, S., Yajnik, C. S., Yuan, J. -M., Zeng, L., Zhang, L., Zhou, J., Amin, N., Asselbergs, F. W., Bakker, S. J. L., Becker, D. M., Lehne, B., Bennett, D. A., van den Berg, L. H., Berndt, S. I., Bharadwaj, D., Bielak, L. F., Bochud, M., Boehnke, M., Bouchard, C., Bradfield, J. P., Brody, J. A., Campbell, A., Carmi, S., Caulfield, M. J., Cesarini, D., Chambers, J. C., Chandak, G. R., Cheng, C. -Y., Ciullo, M., Cornelis, M., Cusi, D., Smith, G. D., Deary, I. J., Dorajoo, R., van Duijn, C. M., Ellinghaus, D., Erdmann, J., Eriksson, J. G., Evangelou, E., Evans, M. K., Faul, J. D., Feenstra, B., Feitosa, M., Foisy, S., Franke, A., Friedlander, Y., Gasparini, P., Gieger, C., Gonzalez, C., Goyette, P., Grant, S. F. A., Griffiths, L. R., Groop, L., Gudnason, V., Gyllensten, U., Hakonarson, H., Hamsten, A., van der Harst, P., Heng, C. -K., Hicks, A. A., Hochner, H., Huikuri, H., Hunt, S. C., Jaddoe, V. W. V., De Jager, P. L., Johannesson, M., Johansson, A., Jonas, J. B., Jukema, J. W., Junttila, J., Kaprio, J., Kardia, S. L. R., Karpe, F., Kumari, M., Laakso, M., van der Laan, S. W., Lahti, J., Laudes, M., Lea, R. A., Lieb, W., Lumley, T., Martin, N. G., Marz, W., Matullo, G., Mccarthy, M. I., Medland, S. E., Merriman, T. R., Metspalu, A., Meyer, B. F., Mohlke, K. L., Montgomery, G. W., Mook-Kanamori, D., Munroe, P. B., North, K. E., Nyholt, D. R., O'Connell, J. R., Ober, C., Oldehinkel, A. J., Palmas, W., Palmer, C., Pasterkamp, G. G., Patin, E., Pennell, C. E., Perusse, L., Peyser, P. A., Pirastu, M., Polderman, T. J. C., Porteous, D. J., Posthuma, D., Psaty, B. M., Rioux, J. D., Rivadeneira, F., Rotimi, C., Rotter, J. I., Rudan, I., Den Ruijter, H. M., Sanghera, D. K., Sattar, N., Schmidt, R., Schulze, M. B., Schunkert, H., Scott, R. A., Shuldiner, A. R., Sim, X., Small, N., Smith, J. A., Sotoodehnia, N., Tai, E. -S., Teumer, A., Timpson, N. J., Toniolo, D., Tregouet, D. -A., Tuomi, T., Vollenweider, P., Wang, C. A., Weir, D. R., Whitfield, J. B., Wijmenga, C., Wong, T. -Y., Wright, J., Yang, J., Yu, L., Zemel, B. S., Zonderman, A. B., Perola, M., Magnusson, P. K. E., Uitterlinden, A. G., Kooner, J. S., Chasman, D. I., Loos, R. J. F., Franceschini, N., Franke, L., Haley, C. S., Hayward, C., Walters, R. G., Perry, J. R. B., Esko, T., Helgason, A., Stefansson, K., Joshi, P. K., Kubo, M., Wilson, J. F., Læknadeild (HÍ), Faculty of Medicine (UI), Félagsfræði-, mannfræði- og þjóðfræðideild (HÍ), Faculty of Sociology, Anthropology and Folkloristics (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), School of Engineering and Natural Sciences (UI), Verkfræði- og náttúruvísindasvið (HÍ), Félagsvísindasvið (HÍ), School of Social Sciences (UI), Háskóli Íslands, University of Iceland, Clark, David W [0000-0002-1025-9185], Okada, Yukinori [0000-0002-0311-8472], Moore, Kristjan H S [0000-0002-9579-4362], Mason, Dan [0000-0002-0026-9216], Pirastu, Nicola [0000-0002-5363-3886], Gandin, Ilaria [0000-0003-3196-2491], Deelen, Patrick [0000-0002-5654-3966], Schurmann, Claudia [0000-0003-4158-9192], Medina-Gomez, Carolina [0000-0001-7999-5538], Karlsson, Robert [0000-0002-8949-2587], Bao, Yanchun [0000-0002-6102-5098], Biino, Ginevra [0000-0002-9936-946X], Brumat, Marco [0000-0003-3268-039X], Chai, Jin-Fang [0000-0003-3770-1137], Eccles, David A [0000-0003-4634-4995], Gordon, Scott D [0000-0001-7623-328X], Harris, Sarah E [0000-0002-4941-5106], Kacprowski, Tim [0000-0002-5393-2413], Karlsson, Torgny [0000-0001-8095-6149], Kleber, Marcus E [0000-0003-0663-7275], Mahajan, Anubha [0000-0001-5585-3420], Matsuda, Koichi [0000-0001-7292-2686], Meng, Weihua [0000-0001-5388-8494], van der Most, Peter J [0000-0001-8450-3518], Munz, Matthias [0000-0002-4728-3357], Palviainen, Teemu [0000-0002-7847-8384], Prasad, Rashmi B [0000-0002-4400-6741], Salvi, Erika [0000-0002-2724-2291], Skotte, Line [0000-0002-7398-1271], van der Spek, Ashley [0000-0001-7136-0159], Spracklen, Cassandra N [0000-0003-3590-7182], Strawbridge, Rona J [0000-0001-8506-3585], Tajuddin, Salman M [0000-0002-7919-8528], Verweij, Niek [0000-0002-4303-7685], Yanek, Lisa R [0000-0001-7117-1075], Zhao, Wei [0000-0001-7388-0692], Albert, Matthew L [0000-0001-7285-6973], Bentley, Amy R [0000-0002-0827-9101], Chanock, Stephen [0000-0002-2324-3393], Chen, Zhengming [0000-0001-6423-105X], Chiu, Yen-Feng [0000-0002-3352-4500], Cocca, Massimiliano [0000-0002-1127-7596], Collins, Francis S [0000-0002-1023-7410], Cugliari, Giovanni [0000-0002-6080-0718], Damulina, Anna [0000-0001-8241-2727], Day, Felix R [0000-0003-3789-7651], Dhana, Klodian [0000-0002-6397-7009], Dzimiri, Nduna [0000-0003-3395-5754], Elliott, Paul [0000-0002-7511-5684], Felix, Janine F [0000-0002-9801-5774], Freedman, Barry I [0000-0003-0275-5530], Girotto, Giorgia [0000-0003-4507-6589], Goel, Anuj [0000-0003-2307-4021], Goodarzi, Mark O [0000-0001-6364-5103], Gudbjartsson, Daniel F [0000-0002-5222-9857], Guity, Kamran [0000-0002-8379-9668], van Heel, David A [0000-0002-0637-2265], Hirata, Makoto [0000-0002-9994-9958], Ikram, M Arfan [0000-0003-0372-8585], Kamatani, Yoichiro [0000-0001-8748-5597], Kanai, Masahiro [0000-0001-5165-4408], Khor, Chiea Chuen [0000-0002-1128-4729], Kolcic, Ivana [0000-0001-7918-6052], Langenberg, Claudia [0000-0002-5017-7344], Lawlor, Deborah A [0000-0002-6793-2262], Liu, Jianjun [0000-0002-3255-3019], London, Stephanie J [0000-0003-4911-5290], Luan, Jian’an [0000-0003-3137-6337], Matoba, Nana [0000-0001-5329-0134], Mei, Xue W [0000-0002-6279-4884], Mezzavilla, Massimo [0000-0002-9000-4595], Milani, Lili [0000-0002-5323-3102], Mori, Trevor A [0000-0002-5264-9229], Murakami, Yoshinori [0000-0002-2826-4396], Murray, Alison D [0000-0003-4915-4847], Mychaleckyj, Josyf C [0000-0003-2595-0005], Neville, Matt J [0000-0002-6004-5433], Nolte, Ilja M [0000-0001-5047-4077], Ong, Ken K [0000-0003-4689-7530], Pálsson, Gunnar [0000-0002-8231-3961], Pankow, James S [0000-0001-7076-483X], Pattaro, Cristian [0000-0002-4119-0109], Quintana-Murci, Lluis [0000-0003-2429-6320], van Rheenen, Wouter [0000-0002-5860-1533], Rich, Stephen S [0000-0003-3872-7793], Rietveld, Cornelius A [0000-0003-4053-1861], Ruggiero, Daniela [0000-0003-3898-7827], Sabanayagam, Charumathi [0000-0002-4042-4719], Sabater-Lleal, Maria [0000-0002-0128-379X], Sala, Cinzia Felicita [0000-0003-2514-2075], Salomaa, Veikko [0000-0001-7563-5324], Scott, Laura J [0000-0002-4886-5084], Sedaghati-Khayat, Bahareh [0000-0002-7665-8648], Sennblad, Bengt [0000-0002-4360-8003], van Setten, Jessica [0000-0002-4934-7510], Smith, Blair H [0000-0002-5362-9430], Stančáková, Alena [0000-0002-1375-0252], Stanton, Alice [0000-0002-4961-165X], Straker, Leon [0000-0002-7786-4128], Sulem, Patrick [0000-0001-7123-6123], Swertz, Morris A [0000-0002-0979-3401], Taylor, Kent D [0000-0002-2756-4370], Tzoulaki, Ioanna [0000-0002-4275-9328], Veldink, Jan H [0000-0001-5572-9657], Vitart, Veronique [0000-0002-4991-3797], Völker, Uwe [0000-0002-5689-3448], Wander, Gurpreet S [0000-0002-4596-4247], Wang, Ya Xing [0000-0003-2749-7793], Wild, Sarah [0000-0001-7824-2569], Yuan, Jian-Min [0000-0002-4620-3108], Asselbergs, Folkert W [0000-0002-1692-8669], Boehnke, Mike [0000-0002-6442-7754], Bouchard, Claude [0000-0002-0048-491X], Brody, Jennifer A [0000-0001-8509-148X], Campbell, Archie [0000-0003-0198-5078], Caulfield, Mark J [0000-0001-9295-3594], Smith, George Davey [0000-0002-1407-8314], Dorajoo, Rajkumar [0000-0001-6608-2051], Ellinghaus, David [0000-0002-4332-6110], Erdmann, Jeanette [0000-0002-4486-6231], Evangelou, Evangelos [0000-0002-5488-2999], Feenstra, Bjarke [0000-0003-1478-649X], Feitosa, Mary [0000-0002-0933-2410], Franke, Andre [0000-0003-1530-5811], Grant, Struan F A [0000-0003-2025-5302], Griffiths, Lyn R [0000-0002-6774-5475], Groop, Leif [0000-0002-0187-3263], Gudnason, Vilmundur [0000-0001-5696-0084], van der Harst, Pim [0000-0002-2713-686X], Heng, Chew-Kiat [0000-0002-7309-9473], Hicks, Andrew A [0000-0001-6320-0411], Jaddoe, Vincent W V [0000-0003-2939-0041], De Jager, Philip L [0000-0002-8057-2505], Johannesson, Magnus [0000-0001-8759-6393], Johansson, Åsa [0000-0002-2915-4498], Jonas, Jost B [0000-0003-2972-5227], Jukema, J Wouter [0000-0002-3246-8359], Kaprio, Jaakko [0000-0002-3716-2455], Laakso, Markku [0000-0002-3394-7749], van der Laan, Sander W [0000-0001-6888-1404], Lahti, Jari [0000-0002-4310-5297], Martin, Nicholas G [0000-0003-4069-8020], Medland, Sarah E [0000-0003-1382-380X], Merriman, Tony R [0000-0003-0844-8726], Metspalu, Andres [0000-0002-3718-796X], Mohlke, Karen L [0000-0001-6721-153X], Montgomery, Grant W [0000-0002-4140-8139], Munroe, Patricia B [0000-0002-4176-2947], Nyholt, Dale R [0000-0001-7159-3040], Ober, Carole [0000-0003-4626-9809], Oldehinkel, Albertine J [0000-0003-3925-3913], Palmer, Colin [0000-0002-6415-6560], Perusse, Louis [0000-0001-6440-9698], Polderman, Tinca J. C. [0000-0001-5564-301X], Porteous, David J [0000-0003-1249-6106], Rioux, John D [0000-0001-7560-8326], Rivadeneira, Fernando [0000-0001-9435-9441], Rotimi, Charles [0000-0001-5759-053X], Rotter, Jerome I [0000-0001-7191-1723], Rudan, Igor [0000-0001-6993-6884], Sattar, Naveed [0000-0002-1604-2593], Sim, Xueling [0000-0002-1233-7642], Smith, Jennifer A [0000-0002-3575-5468], Teumer, Alexander [0000-0002-8309-094X], Timpson, Nicholas J [0000-0002-7141-9189], Tuomi, Tiinamaija [0000-0002-8306-6202], Wang, Carol A [0000-0002-4301-3974], Weir, David R [0000-0002-1661-2402], Whitfield, John B [0000-0002-1103-0876], Magnusson, Patrik K. E. [0000-0002-7315-7899], Uitterlinden, André G [0000-0002-7276-3387], Loos, Ruth J. F. [0000-0002-8532-5087], Franke, Lude [0000-0002-5159-8802], Haley, Chris S [0000-0002-9811-0210], Hayward, Caroline [0000-0002-9405-9550], Walters, Robin G [0000-0002-9179-0321], Joshi, Peter K [0000-0002-6361-5059], Wilson, James F [0000-0001-5751-9178], Apollo - University of Cambridge Repository, Moore, Kristjan HS [0000-0002-9579-4362], Luan, Jian'an [0000-0003-3137-6337], Grant, Struan FA [0000-0003-2025-5302], Jaddoe, Vincent WV [0000-0003-2939-0041], Polderman, Tinca JC [0000-0001-5564-301X], Magnusson, Patrik KE [0000-0002-7315-7899], Loos, Ruth JF [0000-0002-8532-5087], Neurology, Human genetics, Amsterdam Reproduction & Development (AR&D), Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Cardiovascular Centre (CVC), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Stem Cell Aging Leukemia and Lymphoma (SALL), Institute for Molecular Medicine Finland, Department of Psychology and Logopedics, University Management, Developmental Psychology Research Group, Staff Services, Cognitive and Brain Aging, Research Programs Unit, Diabetes and Obesity Research Program, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, Clinicum, University of Helsinki, Centre of Excellence in Complex Disease Genetics, Department of Public Health, Genetic Epidemiology, Helsinki Collegium for Advanced Studies, HUS Abdominal Center, Endokrinologian yksikkö, Bradford Teaching Hospitals NHS Foundation Trust [Bradford, UK] (BTHFT), University of Trieste, Université de Lausanne (UNIL), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Consiglio Nazionale delle Ricerche (CNR), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Institut Pasteur [Paris], University of Oxford [Oxford], Medical Genetics, Dept. RSD and Public Health, IRCCS-Burlo Garofolo/University of Trieste, sans affiliation, Helmholtz-Zentrum München (HZM), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institute of Cardiovascular Science, University College London, Hammersmith Hospital NHS Imperial College Healthcare-Imperial College London, Universität zu Lübeck [Lübeck], University of Ioannina Medical School, Università degli studi di Napoli Federico II-RISSC-Lab, Universität Heidelberg [Heidelberg], University of Turin, University of California-University of California, Nantes Université (NU)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), University of Helsinki-University of Helsinki, Université de Nantes (UN)-Université de Rennes 1 (UR1), Erasmus MC other, Internal Medicine, and Applied Economics
Subjects: 0301 basic medicine, 631/208/1397, Chemistry(all), Health Status, [SDV]Life Sciences [q-bio], LOCI, General Physics and Astronomy, MESH: Haplotype, MESH: Cognition, 030105 genetics & heredity, Runs of Homozygosity, Biochemistry, Consanguinity, Cognition, Inbreeding depression, 2.1 Biological and endogenous factors, Body Size, Inbreeding, Skyldleikarækt, Aetiology, Human phenotypes, lcsh:Science, MESH: Health Status, Genetics, Multidisciplinary, Inbreeding Depression, Confounding, Homozygote, RUNS, 631/208/205, 631/208/721, 3. Good health, genomic inbreeding coefficients, MESH: Risk-Taking, 631/208/730, Autozygosit, homozygosity, Erfðarannsóknir, Medical Genetics, genomic inbreeding coefficient, MESH: Homozygote, Offspring, Science, Autozygosity, Blóðsifjar, 610 Medicine & health, Biology, INBREEDING DEPRESSION, HOMOZYGOSITY, FERTILITY, QUANTIFICATION, Physics and Astronomy(all), General Biochemistry, Genetics and Molecular Biology, Article, Association, 03 medical and health sciences, Risk-Taking, 360 Social problems & social services, Journal Article, Humans, ddc:610, Allele, Alleles, Medicinsk genetik, Genetic association study, MESH: Consanguinity, MESH: Body Size, MESH: Humans, Biochemistry, Genetics and Molecular Biology(all), MESH: Alleles, Haplotype, MESH: Fertility, General Chemistry, Brain Disorders, MESH: Inbreeding Depression, 030104 developmental biology, Fertility, Haplotypes, Genetic markers, lcsh:Q, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 3111 Biomedicine, Genetics and Molecular Biology(all)
Abstract: Publisher's version (útgefin grein)., In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding., This paper is the work of the ROHgen consortium. We thank the Sigma T2D Consortium, whose members are detailed in Supplementary Note 3. We thank the UK Biobank Resource, approved under application 19655; we acknowledge funding from the UK Medical Research Council Human Genetics Unit and MRC Doctoral Training Programme in Precision Medicine. We also thank Neil Robertson, Wellcome Trust Centre for Human Genetics, Oxford, for use of his author details management software, Authorial. Finally, we thank all the participants, researchers and funders of ROHgen cohorts. Cohort-specific acknowledgements are in Supplementary Data 2; personal acknowledgements and disclosures are in Supplementary Note 2. We thank Rachel Edwards for administrative assistance.
Published: 2019

21. Prospective analysis of circulating metabolites and breast cancer in EPIC

Author: José María Huerta, Salvatore Panico, Antonia Trichopoulou, Joseph A. Rothwell, Sabina Sieri, Anja Olsen, Christina C. Dahm, Ruth C. Travis, Audrey Gicquiau, Pilar Amiano, Elisabete Weiderpass, N. Charlotte Onland-Moret, Antonio Agudo, Anna Karakatsani, Isabelle Romieu, Paolo Vineis, Mathilde His, Elio Riboli, Marc J. Gunter, Guri Skeie, Tilman Kühn, Augustin Scalbert, Carla H. van Gils, Georgia Martimianaki, Therese Haugdahl Nøst, Anne Tjønneland, Heiner Boeing, Laure Dossus, Pietro Ferrari, Julie A. Schmidt, Rosario Tumino, Konstantinos K. Tsilidis, David Achaintre, Torkjel M. Sandanger, Agnès Fournier, Sofia Christakoudi, María José Sánchez, Vivian Viallon, Renée T. Fortner, Kim Overvad, Giovanna Masala, Sabina Rinaldi, J. Ramón Quirós, Gianluca Severi, Eva Ardanaz, [His,M, Viallon,V, Dossus,L, Gicquiau,A, Achaintre,D, Scalbert,A, Ferrari,P, Weiderpass,E, Gunter,MJ, Rinaldi,S] International Agency for Research on Cancer, Lyon, France. [Romieu,I] Centre for Research on Population Health, National Institute of Public Health, Cuernavaca, Mexico. [Onland-Moret,NC, van Gils,CH] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands. [Dahm,CC, Overvad,K] Department of Public Health, Aarhus University, Aarhus, Denmark. [Overvad,K] Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark. [Olsen,A, Tjønneland,A] Danish Cancer Society Research Center, Copenhagen, Denmark. [Tjønneland,A] University of Copenhagen, Copenhagen, Denmark. [Fournier,A, Rothwell,JA, Severi,G] CESP, Université Paris-Sud, UVSQ, INSERM, Université Paris-Saclay, Villejuif, France. [Fournier,A, Severi,G] Gustave Roussy, Villejuif, France. [Kühn,T, Fortner,R] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Boeing,H] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany. [Trichopoulou,A, Karakatsani,A, Martimianaki,G] Hellenic Health Foundation, Athens, Greece. [Karakatsani,A] Pulmonary Medicine Department, School of Medicine, National and Kapodistrian University of Athens, 'ATTIKON' University Hospital, Haidari, Greece. [Masala,G] Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network – ISPRO, Florence, Italy. [Sieri,S] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy. [Tumino,R] Cancer Registry and Histopathology Department, 'M.P.Arezzo'Hospital, ASP Ragusa, Ragusa, Italy. [Vineis,P] Italian Institute for Genomic Medicine (IIGM), Turin, Italy. [Vineis,P] MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK. [Panico,S] Dipartimento di medicina clinica e chirurgia, Federico II University, Naples, Italy. [Nøst,TH, Sandanger,TM, Skeie,G] Department of Community Medicine, UiT the Arctic University of Norway, Tromso, Norway. [Skeie,G] Nutritional Epidemiology Group, School of Food Science and Nutrition, University of Leeds, Leeds, UK. [Quirós,JR] Public Health Directorate, Asturias, Spain. [Agudo,A] Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain. [Sánchez,MJ] Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs.GRANADA, Universidad de Granada, Granada, Spain. [Sánchez,MJ, Amiano,P, Huerta,JM, Ardanaz,E] CIBER Epidemiology and Public Health CIBERESP, Madrid, Spain. [Amiano,P] Public Health Division of Gipuzkoa, BioDonostia Research Institute, San Sebastian, Spain. [Huerta,JM] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Ardanaz,E] Navarra Public Health Institute, Pamplona, Spain. [Ardanaz,E] IdiSNA, Navarra Institute for Health Research, Pamplona, Spain. [Schmidt,JA, Travis,RC] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. [Riboli,E, Tsilidis,KK, Christakoudi,S] Department of Epidemiology and Biostatistics, Imperial College London, St Mary’s Campus, Norfolk Place, London, UK. [Tsilidis,KK] Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece. [Christakoudi,S] MRC Centre for Transplantation, King’s College London, Great Maze Pond, London, SE1 9RT, UK, This work was funded by the French National Cancer Institute (grant number 2015-166). The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), European Research Council (ERC-2009-AdG 232997), and Nordforsk, Nordic Centre of Excellence Programme on Food, Nutrition and Health (Norway), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236), Navarra, and the CERCA Program (Generalitat de Catalunya) (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), and Cancer Research UK (14136 to EPIC-Norfolk, and C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom).
Subjects: 0301 basic medicine, Oncology, lcsh:Medicine, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Mass Spectrometry, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Cohort Studies, 0302 clinical medicine, Breast cancer, Information Science::Information Science::Data Collection::Vital Statistics::Morbidity::Incidence [Medical Subject Headings], Risk Factors, Estudios prospectivos, Prospective Studies, Prospective cohort study, 11 Medical and Health Sciences, Persons::Persons::Age Groups::Adult::Aged [Medical Subject Headings], education.field_of_study, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings], VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, Incidence, Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biochemistry::Metabolomics [Medical Subject Headings], General Medicine, Metabolómica, Middle Aged, metabolomics, 3. Good health, Research Design, 030220 oncology & carcinogenesis, Cohort, Neoplasias de la mama, Female, Chemicals and Drugs::Biological Factors::Biological Markers::Biomarkers, Pharmacological [Medical Subject Headings], Cohort study, Research Article, prospective study, Adult, medicine.medical_specialty, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], Population, Breast Neoplasms, Càncer de mama, 03 medical and health sciences, breast cancer, Internal medicine, Cell Line, Tumor, General & Internal Medicine, medicine, Journal Article, Metabolomics, Humans, Prospective study, education, Persons::Persons::Age Groups::Adult [Medical Subject Headings], Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Aged, business.industry, lcsh:R, Case-control study, Cancer, Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Odds ratio, medicine.disease, 030104 developmental biology, Check Tags::Female [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Case-Control Studies, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Chemistry Techniques, Analytical::Mass Spectrometry [Medical Subject Headings], Biomarkers
Abstract: BackgroundMetabolomics is a promising molecular tool to identify novel etiologic pathways leading to cancer. Using a targeted approach, we prospectively investigated the associations between metabolite concentrations in plasma and breast cancer risk.MethodsA nested case-control study was established within the European Prospective Investigation into Cancer cohort, which included 1624 first primary incident invasive breast cancer cases (with known estrogen and progesterone receptor and HER2 status) and 1624 matched controls. Metabolites (n = 127, acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexose, sphingolipids) were measured by mass spectrometry in pre-diagnostic plasma samples and tested for associations with breast cancer incidence using multivariable conditional logistic regression.ResultsAmong women not using hormones at baseline (n = 2248), and after control for multiple tests, concentrations of arginine (odds ratio [OR] per SD = 0.79, 95% confidence interval [CI] = 0.70–0.90), asparagine (OR = 0.83 (0.74–0.92)), and phosphatidylcholines (PCs) ae C36:3 (OR = 0.83 (0.76–0.90)), aa C36:3 (OR = 0.84 (0.77–0.93)), ae C34:2 (OR = 0.85 (0.78–0.94)), ae C36:2 (OR = 0.85 (0.78–0.88)), and ae C38:2 (OR = 0.84 (0.76–0.93)) were inversely associated with breast cancer risk, while the acylcarnitine C2 (OR = 1.23 (1.11–1.35)) was positively associated with disease risk. In the overall population, C2 (OR = 1.15 (1.06–1.24)) and PC ae C36:3 (OR = 0.88 (0.82–0.95)) were associated with risk of breast cancer, and these relationships did not differ by breast cancer subtype, age at diagnosis, fasting status, menopausal status, or adiposity.ConclusionsThese findings point to potentially novel pathways and biomarkers of breast cancer development. Results warrant replication in other epidemiological studies.
Published: 2019

22. Impact of age on the use of adjuvant treatments in patients undergoing surgery for colorectal cancer: patients with stage III colon or stage II/III rectal cancer

Author: C. Sarasqueta, A. Perales, A. Escobar, M. Baré, M. Redondo, N. Fernández de Larrea, E. Briones, J. M. Piera, M. V. Zunzunegui, J. M. Quintana, the REDISECC-CARESS/CCR group, Instituto de Salud Carlos III, Basque Government (España), Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), REDISECC-CARESS/CCR group, [Sarasqueta,C, Perales,A] Biodonostia Health Research Institute - Donostia University Hospital / Red de Investigación en Servicios de Salud en Enfermedades Crónicas (REDISSEC), Donostia-San Sebastián, Gipuzkoa, Spain. [Escobar,A] Research Unit, Hospital Basurto / Red de Investigación en Servicios de Salud en Enfermedades Crónicas (REDISSEC), Bilbao, Bizkaia, Spain. [Baré,M] Clinical Epidemiology and Cancer Screening, Corporació Sanitaria Parc Taulí / Red de Investigación en Servicios de Salud en Enfermedades Crónicas (REDISSEC), Sabadell, Barcelona, Spain. [Redondo,M] Research Unit, Costa del Sol Hospital / Red de Investigación en Servicios de Salud en Enfermedades Crónicas (REDISSEC), Marbella, Málaga, Spain. [Fernández de Larrea,N] Cancer and Environmental Epidemiology Unit, National Center for Epidemiology, Instituto de Salud Carlos III / Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain. [Briones,E] Epidemiology Unit, Seville Health District, Andalusian Health Service / Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Seville, Spain. [Piera,JM] Medical Oncology Unit, Donostia University Hospital, Donostia-San Sebastián, Gipuzkoa, Spain. [Zunzunegui,MV] Departement de médecine sociale et préventive Institut de recherche en santé publique (IRSPUM), University of Montréal, Montréal, Québec, Canada. [Quintana,JM] Research Unit, Galdakao-Usansolo Hospital / REDISSEC, Labeaga Auzoa, 48960, Galdakao, Bizkaia, Spain., Eusko Jaurlaritza, and European Commission
Subjects: Male, 0301 basic medicine, Cancer Research, Colorectal cancer, medicine.medical_treatment, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Combined Modality Therapy::Chemotherapy, Adjuvant [Medical Subject Headings], Quimioterapia adyuvante, Comorbidity, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Combined Modality Therapy::Neoadjuvant Therapy [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Neoplasias colorrectales, Surgical oncology, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Epidemiologic Factors::Comorbidity [Medical Subject Headings], Antineoplastic agents, Medicine, Prospective Studies, Stage (cooking), Prospective cohort study, Colectomy, Persons::Persons::Age Groups::Adult::Aged [Medical Subject Headings], Aged, 80 and over, Proctectomy, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Epidemiologic Factors::Age Factors [Medical Subject Headings], Age Factors, Equity, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Neoadjuvant Therapy, Oncology, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Colonic Neoplasms, Practice Guidelines as Topic, Female, Drug therapy, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Neoplasm Staging [Medical Subject Headings], Colorectal Neoplasms, Adjuvant, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Digestive System Surgical Procedures::Colectomy [Medical Subject Headings], Research Article, medicine.medical_specialty, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], lcsh:RC254-282, Health Care::Health Services Administration::Quality of Health Care::Quality Assurance, Health Care::Guidelines as Topic::Practice Guidelines as Topic [Medical Subject Headings], 03 medical and health sciences, Age, Genetics, Anthropology, Education, Sociology and Social Phenomena::Social Sciences::Sociology::Socioeconomic Factors [Medical Subject Headings], Chemotherapy, Humans, Aged, Neoplasm Staging, Rectal Neoplasms, business.industry, Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [Medical Subject Headings], Odds ratio, Antineoplásicos, medicine.disease, Surgery, 030104 developmental biology, Check Tags::Female [Medical Subject Headings], Socioeconomic Factors, Persons::Persons::Age Groups::Adult::Aged::Aged, 80 and over [Medical Subject Headings], Adherence, Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms::Colonic Neoplasms [Medical Subject Headings], Quimioterapia, business, Preoperative radiotherapy
Abstract: Consortia: The REDISECC-CARESS/CCR group: Jose María Quintana, Marisa Baré, Maximino Redondo, Eduardo Briones Pérez de la Briones, Nerea Fernández de Larrea, Cristina Sarasqueta, Antonio Escobar , Francisco Rivas, Maria Morales-Suárez, Juan Antonio Blasco, Isabel del Cura , Inmaculada Arostegui, Amaia Bilbao, Nerea González , Susana García-Gutiérrez, Iratxe Lafuente, Urko Aguirre, Miren Orive, Josune Martin, Ane Antón-Ladislao, Núria Torà, Marina Pont, María Purificación Martínez del, Alberto Loizate, Ignacio Zabalza, José Errasti, Antonio Gimeno, Santiago Lázaro, Mercè Comas, Jose María Enríquez-Navascues, Carlos Placer, Amaia Perales, Iñaki Urkidi, Jose María Erro, Enrique Cormenzana, Adelaida Lacasta, Pep Piera, Elena Campano, Ana Isabel Sotelo, Segundo Gómez-Abril, F. Medina-Cano, Julia Alcaide, Arturo Del Rey-Moreno, Manuel Jesús Alcántara, Rafael Campo, Alex Casalots, Carles Pericay, Maria José Gil, Miquel Pera, Pablo Collera, Josep Alfons Espinàs, Mercedes Martínez, Mireia Espallargues, Caridad Almazán, Paula Dujovne, José María Fernández-Cebrián, Rocío Anula, Julio Mayol, Ramón Cantero, Héctor Guadalajara, María Alexandra Heras, Damián García, Mariel Morey & Alberto Colina., [Background]: Many older patients don’t receive appropriate oncological treatment. Our aim was to analyse whether there are age differences in the use of adjuvant chemotherapy and preoperative radiotherapy in patients with colorectal cancer., [Methods]: A prospective cohort study was conducted in 22 hospitals including 1157 patients with stage III colon or stage II/III rectal cancer who underwent surgery. Primary outcomes were the use of adjuvant chemotherapy for stage III colon cancer and preoperative radiotherapy for stage II/III rectal cancer. Generalised estimating equations were used to adjust for education, living arrangements, area deprivation, comorbidity and clinical tumour characteristics., [Results]: In colon cancer 92% of patients aged under 65 years, 77% of those aged 65 to 80 years and 27% of those aged over 80 years received adjuvant chemotherapy (χ2trends, [Conclusions]: The probability of older patients with colorectal cancer receiving adjuvant chemotherapy and preoperative radiotherapy is lower than that of younger patients; many of them are not receiving the treatments recommended by clinical practice guidelines. Differences in comorbidity, tumour characteristics, curative resection, and socioeconomic factors do not explain this lower probability of treatment. Research is needed to identify the role of physical and cognitive functional status, doctors’ attitudes, and preferences of patients and their relatives, in the use of adjuvant therapies., This work was supported in part by grants from the Spanish Health Research Fund (PS09/00314, PS09/00910, PS09/00746, PS09/00805, PI09/90460, PI09/90490, PI09/90397, PI09/90453, PI09/90441); Department of Health of the Basque Country (2010111098); KRONIKGUNE–Research Centre on Chronicity (KRONIK 11/006); and the European Regional Development Fund.
Published: 2019

23. Epigenome-wide association study for lifetime estrogen exposure identifies an epigenetic signature associated with breast cancer risk

Author: Cyrille Cuenin, Salvatore Panico, Rosario Tumino, Anthony J. Swerdlow, Domenico Palli, Pierre Antoine Dugué, Nick Orr, Sara Grioni, Michael Jones, Francesca Fasanelli, Isabelle Romieu, Silvia Polidoro, Vittorio Perduca, Srikant Ambatipudi, Melissa C. Southey, Minouk J. Schoemaker, Olivia Fletcher, Graham G. Giles, Paolo Vineis, Maria Concetta Giurdanella, Giovanna Masala, James M. Flanagan, Annelie Johansson, Amalia Mattiello, Nichola Johnson, Dallas R. English, Gianluca Severi, Katarzyna Tomczyk, Roger L. Milne, Carlotta Sacerdote, Claudia Agnoli, Laura Baglietto, Veronique Chajes, Zdenko Herceg, Breast Cancer Now, Molecular and Nutritional Epidemiology Unit, CSPO-Scientific Institute of Tuscany, Molecular and Nutritional Epidemiology Unit (ISPO), Cancer Research and Prevention Institute, Epidemiology, Fondazione IRCCS Istituto Nazionale dei Tumori, Cancer Registry and Histopathology Unit, Civile - M.P.Arezzo Hospital, Cancer Registry, Center for Cancer Prevention, CPO-Piemonte, Department of Clinical and Experimental Medicine, Università degli studi di Napoli Federico II, Human Genetics Foundation (HuGeF), Torino, Italy., The institute of cancer research [London], Clinical Genetics Branch, Division of Cancer Epidemiology & Genetics, National Institutes of Health [Bethesda] (NIH)-National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Université Paris Descartes - Paris 5 (UPD5)-Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS), Cancer Epidemiology Centre, Cancer Council of Victoria, Melbourne, Australia, parent, entre for Molecular, Environmental, Genetic and Analytic (MEGA) Epidemiology, University of Melbourne, Cancer Epidemiology Centre, Cancer Council Victoria, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), International Agency for Cancer Research (IACR), Epidemiology section, Institute of Cancer Research in Sutton, University of Torino and CPO-Piemonte, Università degli studi di Torino (UNITO), Perduca, Vittorio, University of Naples Federico II = Università degli studi di Napoli Federico II, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), and Università degli studi di Torino = University of Turin (UNITO)
Subjects: BIOMARKER, 0301 basic medicine, Oncology, Bisulfite sequencing, Epigenesis, Genetic, Cancer risk, REANALYSIS, Breast cancer, 0302 clinical medicine, [STAT.AP] Statistics [stat]/Applications [stat.AP], Prospective Studies, skin and connective tissue diseases, Prospective cohort study, Genetics (clinical), Genetics & Heredity, [STAT.AP]Statistics [stat]/Applications [stat.AP], OUTCOMES, DNA methylation, WOMEN, Middle Aged, Biomarker, Epigenetics, Estrogen exposure, EWAS, Hormonal exposures, 3. Good health, Italy, CpG site, 030220 oncology & carcinogenesis, Female, Life Sciences & Biomedicine, medicine.medical_specialty, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, PERIPHERAL-BLOOD, 03 medical and health sciences, AGE, [SDV.CAN] Life Sciences [q-bio]/Cancer, SDG 3 - Good Health and Well-being, Internal medicine, Genetics, medicine, Humans, Genetic Predisposition to Disease, Molecular Biology, METAANALYSIS, Science & Technology, business.industry, Research, Case-control study, Cancer, Estrogens, medicine.disease, BODY-MASS INDEX, 030104 developmental biology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Case-Control Studies, CpG Islands, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, SEX-HORMONES, business, Genome-Wide Association Study, Developmental Biology
Abstract: Background It is well established that estrogens and other hormonal factors influence breast cancer susceptibility. We hypothesized that a woman’s total lifetime estrogen exposure accumulates changes in DNA methylation, detectable in the blood, which could be used in risk assessment for breast cancer. Methods An estimated lifetime estrogen exposure (ELEE) model was defined using epidemiological data from EPIC-Italy (n = 31,864). An epigenome-wide association study (EWAS) of ELEE was performed using existing Illumina HumanMethylation450K Beadchip (HM450K) methylation data obtained from EPIC-Italy blood DNA samples (n = 216). A methylation index (MI) of ELEE based on 31 CpG sites was developed using HM450K data from EPIC-Italy and the Generations Study and evaluated for association with breast cancer risk in an independent dataset from the Generations Study (n = 440 incident breast cancer cases matched to 440 healthy controls) using targeted bisulfite sequencing. Lastly, a meta-analysis was conducted including three additional cohorts, consisting of 1187 case-control pairs. Results We observed an estimated 5% increase in breast cancer risk per 1-year longer ELEE (OR = 1.05, 95% CI 1.04–1.07, P = 3 × 10−12) in EPIC-Italy. The EWAS identified 694 CpG sites associated with ELEE (FDR Q
Published: 2019

24. KIM-1 as a blood-based marker for early detection of kidney cancer: a prospective nested case–control study

Author: Roel Vermeulen, Prateek Khanna, David C. Muller, Paolo Vineis, Antonio Agudo, Heiner Boeing, Rupal S. Bhatt, Elio Riboli, Joseph V. Bonventre, Domenico Palli, Amanda J. Cross, Antonia Trichopoulou, H. Bas Bueno-de-Mesquita, Maria Dolores Chirlaque, Kim Overvad, Timothy J. Key, Therese Haugdahl Nøst, Anna Karakatsani, Sabina Sieri, Ghislaine Scelo, Paul Brennan, Konstantinos K. Tsilidis, Torkjel M. Sandanger, Elisabete Weiderpass, Mattias Johansson, Salvatore Panico, J. Ramón Quirós, Gianluca Severi, Marina Kvaskoff, Venkata S. Sabbisetti, Vittorio Perduca, Miguel Rodríguez-Barranco, Carlo La Vecchia, Petra H.M. Peeters, Unit of Nutrition and Cancer, International Agency for Cancer Research (IACR), Centre for Environment and Health, Imperial College London-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU), Unit of Environment Cancer Epidemiology, IARC, Danish Cancer Society Research Center, Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Section of Epidemiology, Aarhus University [Aarhus], National Institute for Public Health and the Environment [Bilthoven] (RIVM), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Université Paris Descartes - Paris 5 (UPD5)-Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS), Nutrition, hormones et cancer: épidémiologie et prévention (E3N), Epidémiologie, sciences sociales, santé publique (IFR 69), Université Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Mode de vie, génétique et santé : études intégratives et transgénérationnelles (U1018 (Équipe 9)), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR), Istituto Mario Negri and Universita di Milano, Istituto Mario Negri and Università di Milano, Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Department of Clinical and Experimental Medicine, Università degli studi di Napoli Federico II, Genetic Epidemiology Group [Helsinki], Folkhälsan Research Center, Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki-Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, Unit of Nutrition, Environment and Cancer, Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Consorcio de Investigación Biomédica en Red especializado en Epidemiología y Salud Pública (CIBERESP), Los Centros de Investigación Biomédica en Red (CIBER), Cancer Epidemiology Unit, University of Oxford [Oxford], Harvard Medical School [Boston] (HMS), Cancer Research UK, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Gustave Roussy (IGR), One Health Chemisch, dIRAS RA-2, Scelo, Ghislaine, Muller, David C, Riboli, Elio, Johansson, Mattia, Cross, Amanda J, Vineis, Paolo, Tsilidis, Konstantinos K, Brennan, Paul, Boeing, Heiner, Peeters, Petra H M, Vermeulen, Roel C H, Overvad, Kim, Bueno-de-Mesquita, H Ba, Severi, Gianluca, Perduca, Vittorio, Kvaskoff, Marina, Trichopoulou, Antonia, La Vecchia, Carlo, Karakatsani, Anna, Palli, Domenico, Sieri, Sabina, Panico, Salvatore, Weiderpass, Elisabete, Sandanger, Torkjel M, Nøst, Therese H, Agudo, Antonio, Quirós, J Ramón, Rodríguez-Barranco, Miguel, Chirlaque, Maria-Dolore, Key, Timothy J, Khanna, Prateek, Bonventre, Joseph V, Sabbisetti, Venkata S, and Bhatt, Rupal S
Subjects: BIOMARKER, Oncology, Male, Cancer Research, 030232 urology & nephrology, urologic and male genital diseases, Rate ratio, 0302 clinical medicine, Renal cell carcinoma, Hepatitis A Virus Cellular Receptor 1, Prospective cohort study, ComputingMilieux_MISCELLANEOUS, Early Detection of Cancer, 2. Zero hunger, education.field_of_study, Incidence (epidemiology), Prognosis, female genital diseases and pregnancy complications, Kidney Neoplasms, 3. Good health, 030220 oncology & carcinogenesis, Cohort, Female, Life Sciences & Biomedicine, INJURY MOLECULE-1, medicine.medical_specialty, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Article, 03 medical and health sciences, Internal medicine, medicine, Biomarkers, Tumor, Humans, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, education, neoplasms, Carcinoma, Renal Cell, Survival analysis, Neoplasm Staging, Science & Technology, business.industry, medicine.disease, ROC Curve, Case-Control Studies, Nested case-control study, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Follow-Up Studies
Abstract: Purpose: Renal cell carcinoma (RCC) has the potential for cure with surgery when diagnosed at an early stage. Kidney injury molecule-1 (KIM-1) has been shown to be elevated in the plasma of RCC patients. We aimed to test whether plasma KIM-1 could represent a means of detecting RCC prior to clinical diagnosis. Experimental Design: KIM-1 concentrations were measured in prediagnostic plasma from 190 RCC cases and 190 controls nested within a population-based prospective cohort study. Cases had entered the cohort up to 5 years before diagnosis, and controls were matched on cases for date of birth, date at blood donation, sex, and country. We applied conditional logistic regression and flexible parametric survival models to evaluate the association between plasma KIM-1 concentrations and RCC risk and survival. Results: The incidence rate ratio (IRR) of RCC for a doubling in KIM-1 concentration was 1.71 [95% confidence interval (CI), 1.44–2.03, P = 4.1 × 10−23], corresponding to an IRR of 63.3 (95% CI, 16.2–246.9) comparing the 80th to the 20th percentiles of the KIM-1 distribution in this sample. Compared with a risk model including known risk factors of RCC (age, sex, country, body mass index, and tobacco smoking status), a risk model additionally including KIM-1 substantially improved discrimination between cases and controls (area under the receiver-operating characteristic curve of 0.8 compared with 0.7). High plasma KIM-1 concentrations were also associated with poorer survival (P = 0.0053). Conclusions: Plasma KIM-1 concentrations could predict RCC incidence up to 5 years prior to diagnosis and were associated with poorer survival. Clin Cancer Res; 24(22); 5594–601. ©2018 AACR.
Published: 2019

25. Association of Selenoprotein and Selenium Pathway Genotypes with Risk of Colorectal Cancer and Interaction with Selenium Status

Author: Krasimira Aleksandrova, Leila Lujan-Barroso, Kim Overvad, Marc J. Gunter, Jeb Jones, Anna Karakatsani, Giovanna Masala, J. Ramón Quirós, John E. Hesketh, José María Huerta, Sophia Harlid, Aurelio Barricarte, Salvatore Panico, Anastasia Kotanidou, Kostas Tsilidis, Afshan Siddiq, Bas Bueno-de-Mesquita, Dagfinn Aune, Tilman Kühn, Therese Haugdahl Nøst, Guri Skeie, Mazda Jenab, Kay-Tee Khaw, Catherine Méplan, Marie-Christine Boutron-Ruault, Elio Riboli, Hanane Omichessan, Rosario Tumino, Antonia Trichopoulou, Wanzhe Zhu, Heinz Freisling, Claudia Agnoli, Nicholas J. Wareham, Alessio Naccarati, Kathryn E. Bradbury, Miguel Rodríguez-Barranco, Neil Murphy, Verena Katzke, Elisabete Weiderpass, Veronika Fedirko, Björn Gylling, Vittorio Perduca, Roel Vermeulen, Sandra Hybsier, Anne Tjønneland, David J. Hughes, Lutz Schomburg, Department of Medical and Clinical Genetics, Medicum, Faculty of Medicine, International Agency for Cancer Research (IACR), Experimental Endocrinology, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Imperial College London, Department of Clinical Epidemiology, Aarhus University Hospital, Institute of Cancer Epidemiology, Danish Cancer Society, Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Université Paris Descartes - Paris 5 (UPD5)-Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS), Nutrition, hormones et cancer: épidémiologie et prévention (E3N), Epidémiologie, sciences sociales, santé publique (IFR 69), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Thermo Fisher Scientific, Thermo Fisher Scientific Inc., Division of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department of Epidemiology, Deutsches Institut für Ernahrungsforschung Potsdam-Rehbrücke (DIFE), Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School [Athens], Cancer Registry and Histopathology Unit, Civile - M.P.Arezzo Hospital, Department of Clinical and Experimental Medicine, Università degli studi di Napoli Federico II, Molecular and Nutritional Epidemiology Unit (ISPO), Cancer Research and Prevention Institute, Fondazione IRCCS Istituto Nazionale dei Tumori, National Institute for Public Health and the Environment [Bilthoven] (RIVM), Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Institute of Community Medicine, University of Tromsø (UiT), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), CIBER de Epidemiología y Salud Pública (CIBERESP), Danish Cancer Society Research Center, MRC epidemiology Unit, Addenbrooke's Hospital, Clinical Gerontology Unit, University of Cambridge [UK] (CAM), Nutrition and Metabolism Section, University of Oxford [Oxford], Department of Epidemiology and Biostatistics, School of Cellular and Molecular Biosciences, Newcastle University [Newcastle], Charite Medical School Berlin, Aalborg Hospital-Aarhus University Hospital, Université Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), 'Civile M.P.Arezzo' hospital, Jones, Jeb S [0000-0001-9165-1658], Schomburg, Lutz [0000-0001-9445-1555], Perduca, Vittorio [0000-0003-0339-0473], Tumino, Rosario [0000-0003-2666-414X], Agnoli, Claudia [0000-0003-4472-1179], Weiderpass, Elisabete [0000-0003-2237-0128], Skeie, Guri [0000-0003-2476-4251], Lujan-Barroso, Leila [0000-0001-6224-1764], Huerta, José María [0000-0002-9637-3869], Rodríguez-Barranco, Miguel [0000-0002-9972-9779], Gylling, Björn [0000-0002-4688-8952], Harlid, Sophia [0000-0001-8540-6891], Freisling, Heinz [0000-0001-8648-4998], Hughes, David J [0000-0003-1668-8770], and Apollo - University of Cambridge Repository
Subjects: 0301 basic medicine, Male, Colorectal cancer, selenoprotein P, SUSCEPTIBILITY, Selenoprotein gene variation, Cohort Studies, Epidemiologia genètica, 0302 clinical medicine, GENETIC-VARIANTS, Genetic epidemiology, Prospective Studies, Selenoproteins, selenium, ComputingMilieux_MISCELLANEOUS, Genetics, chemistry.chemical_classification, ARCHITECTURE, Nutrition and Dietetics, integumentary system, Selenoprotein P, Middle Aged, VDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710, CROHNS-DISEASE, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Näringslära, selenium pathway, 030220 oncology & carcinogenesis, selenium status, Female, HEALTH, Selenium status, 3143 Nutrition, Life Sciences & Biomedicine, lcsh:Nutrition. Foods and food supply, FRIZZLED-RELATED PROTEIN, Adult, MEGALIN, genetic epidemiology, Genotype, BIOMARKERS, prospective cohort, Nutritional Status, Environmental Sciences & Ecology, lcsh:TX341-641, Single-nucleotide polymorphism, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Polymorphism, Single Nucleotide, selenoprotein gene variation, Colorectal cancer risk, Article, Colorectal neoplasms, 03 medical and health sciences, Selenium, Seleni, Càncer colorectal, Selenium pathway, medicine, SNP, Humans, Genetic Predisposition to Disease, METAANALYSIS, Aged, Science & Technology, Nutrition & Dietetics, colorectal cancer risk, VDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710, colorectal neoplasms, Prospective cohort, medicine.disease, POLYMORPHISM, biomarkers, 030104 developmental biology, Frzb, chemistry, Gene Expression Regulation, 3121 General medicine, internal medicine and other clinical medicine, 1111 Nutrition and Dietetics, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Selenoprotein, Environmental Sciences, 0908 Food Sciences, Genètica, Biomarkers, Food Science
Abstract: Selenoprotein genetic variations and suboptimal selenium (Se) levels may contribute to the risk of colorectal cancer (CRC) development. We examined the association between CRC risk and genotype for single nucleotide polymorphisms (SNPs) in selenoprotein and Se metabolic pathway genes. Illumina Goldengate assays were designed and resulted in the genotyping of 1040 variants in 154 genes from 1420 cases and 1421 controls within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Multivariable logistic regression revealed an association of 144 individual SNPs from 63 Se pathway genes with CRC risk. However, regarding the selenoprotein genes, only TXNRD1 rs11111979 retained borderline statistical significance after adjustment for correlated tests (PACT = 0.10, PACT significance threshold was P &lt, 0.1). SNPs in Wingless/Integrated (Wnt) and Transforming growth factor (TGF) beta-signaling genes (FRZB, SMAD3, SMAD7) from pathways affected by Se intake were also associated with CRC risk after multiple testing adjustments. Interactions with Se status (using existing serum Se and Selenoprotein P data) were tested at the SNP, gene, and pathway levels. Pathway analyses using the modified Adaptive Rank Truncated Product method suggested that genes and gene x Se status interactions in antioxidant, apoptosis, and TGF-beta signaling pathways may be associated with CRC risk. This study suggests that SNPs in the Se pathway alone or in combination with suboptimal Se status may contribute to CRC development.
Published: 2019

26. Associations of circulating very-long-chain saturated fatty acids and incident type 2 diabetes:a pooled analysis of prospective cohort studies

Author: Matti Marklund, Sari Voutilainen, Claudine Berr, Nicholas J. Wareham, Dariush Mozaffarian, Albert Koulman, Cécilia Samieri, Ingeborg A. Brouwer, Jenna Veenstra, Amanda M. Fretts, Luc Djoussé, David S. Siscovick, V. Gudnason, Lynne E. Wagenknecht, Lyn M. Steffen, Maria Lankinen, Michael Y. Tsai, Nathan L. Tintle, Nona Sotoodehnia, Jyrki K. Virtanen, Fumiaki Imamura, Barbara McKnight, Catherine Helmer, Kuo-Liong Chien, Kerry L. M. Wong, Jason H Y Wu, Rozenn N. Lemaitre, Bill Harris, Chaoyu Yu, Renata Micha, Matti Uusitupa, Tamara B. Harris, Kalina Rajaobelina, Nita G. Forouhi, Alexis C. Wood, Waqas Qureshi, Rachel A. Murphy, Markku Laakso, Brian T. Steffen, Anya Kalsbeek, Cardiovascular Health Research Unit [Seattle, WA, USA] (Department of Medicine), University of Washington [Seattle], MRC Integrative Epidemiology Unit [Bristol, Royaume-Uni] (MRC IEU), University of Bristol [Bristol], Departments of Epidemiology and Nutrition, Harvard School of Public Health, MRC Epidemiology Unit, University of Cambridge [UK] (CAM)-Institute of Metabolic Science, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), National Institute on Aging [Bethesda, USA] (NIA), National Institutes of Health [Bethesda] (NIH), MRC epidemiology Unit, Addenbrooke's Hospital, Department of Medicine, Kuopio University Hospital, NIHR Core Metabolomics and Lipidomics Laboratory, University of Cambridge, Epidémiologie, santé publique et développement, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR99-ISPED, Icelandic Heart Association, Kopavogur, Iceland., School of Public Health and Clinical Nutrition, University of Eastern Finland, Laboratory Medicine and Pathology in Minnesota [Rochester], Mayo Clinic, Institute of Public Health and Clinical Nutrition, Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Berr, Claudine, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition and Health, APH - Health Behaviors & Chronic Diseases, and APH - Mental Health
Subjects: Adult, Male, medicine.medical_specialty, Percentile, [SDV]Life Sciences [q-bio], Medicine (miscellaneous), Lignoceric acid, 030209 endocrinology & metabolism, Type 2 diabetes, Lower risk, Logistic regression, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Eicosanoic Acids, Internal medicine, Diabetes mellitus, Medicine, Humans, saturated fatty acids, Prospective Studies, Prospective cohort study, 030304 developmental biology, Aged, 2. Zero hunger, Aged, 80 and over, 0303 health sciences, Nutrition and Dietetics, Fatty Acids and Outcomes Research Consortium, diabetes, business.industry, Fatty Acids, Middle Aged, medicine.disease, 3. Good health, very-long-chain saturated fatty acids, [SDV] Life Sciences [q-bio], meta-analysis, Original Research Communications, chemistry, Diabetes Mellitus, Type 2, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Meta-analysis, Cohorts for Heart and Aging Research in Genomic Epidemiology, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: International audience; BACKGROUND:Saturated fatty acids (SFAs) of different chain lengths have unique metabolic and biological effects, and a small number of recent studies suggest that higher circulating concentrations of the very-long-chain SFAs (VLSFAs) arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0) are associated with a lower risk of diabetes. Confirmation of these findings in a large and diverse population is needed.OBJECTIVE:We investigated the associations of circulating VLSFAs 20:0, 22:0, and 24:0 with incident type 2 diabetes in prospective studies.METHODS:Twelve studies that are part of the Fatty Acids and Outcomes Research Consortium participated in the analysis. Using Cox or logistic regression within studies and an inverse-variance-weighted meta-analysis across studies, we examined the associations of VLSFAs 20:0, 22:0, and 24:0 with incident diabetes among 51,431 participants.RESULTS:There were 14,276 cases of incident diabetes across participating studies. Higher circulating concentrations of 20:0, 22:0, and 24:0 were each associated with a lower risk of incident diabetes. Pooling across cohorts, the RR (95% CI) for incident diabetes comparing the 90th percentile to the 10th percentile was 0.78 (0.70, 0.87) for 20:0, 0.84 (0.77, 0.91) for 22:0, and 0.75 (0.69, 0.83) for 24:0 after adjustment for demographic, lifestyle, adiposity, and other health factors. Results were fully attenuated in exploratory models that adjusted for circulating 16:0 and triglycerides.CONCLUSIONS:Results from this pooled analysis indicate that higher concentrations of circulating VLSFAs 20:0, 22:0, and 24:0 are each associated with a lower risk of diabetes.
Published: 2019

27. The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Author: Figlioli, G., Bogliolo, M., Catucci, I., Caleca, L., Lasheras, S. V., Pujol, R., Kiiski, J. I., Muranen, T. A., Barnes, D. R., Dennis, J., Michailidou, K., Bolla, M. K., Leslie, G., Aalfs, C. M., Balleine, R., Baxter, R., Braye, S., Carpenter, J., Dahlstrom, J., Forbes, J., Lee, C. S., Marsh, D., Morey, A., Pathmanathan, N., Scott, R., Simpson, P., Spigelman, A., Wilcken, N., Yip, D., Zeps, N., Adank, M. A., Adlard, J., Agata, S., Cadoo, K., Agnarsson, B. A., Ahearn, T., Aittomaki, K., Ambrosone, C. B., Andrews, L., Anton-Culver, H., Antonenkova, N. N., Arndt, V., Arnold, N., Aronson, K. J., Arun, B. K., Asseryanis, E., Auber, B., Auvinen, P., Azzollini, J., Balmana, J., Barkardottir, R. B., Barrowdale, D., Barwell, J., Beane Freeman, L. E., Beauparlant, C. J., Beckmann, M. W., Behrens, S., Benitez, J., Berger, R., Bermisheva, M., Blanco, A. M., Blomqvist, C., Bogdanova, N. V., Bojesen, A., Bojesen, S. E., Bonanni, B., Borg, A., Brady, A. F., Brauch, H., Brenner, H., Bruning, T., Burwinkel, B., Buys, S. S., Caldes, T., Caliebe, A., Caligo, M. A., Campa, D., Campbell, I. G., Canzian, F., Castelao, J. E., Chang-Claude, J., Chanock, S. J., Claes, K. B. M., Clarke, C. L., Collavoli, A., Conner, T. A., Cox, D. G., Cybulski, C., Czene, K., Daly, M. B., de la Hoya, M., Devilee, P., Diez, O., Ding, Y. C., Dite, G. S., Ditsch, N., Domchek, S. M., Dorfling, C. M., dos-Santos-Silva, I., Durda, K., Dwek, M., Eccles, D. M., Ekici, A. B., Eliassen, A. H., Ellberg, C., Eriksson, M., Evans, D. G., Fasching, P. A., Figueroa, J., Flyger, H., Foulkes, W. D., Friebel, T. M., Friedman, E., Gabrielson, M., Gaddam, P., Gago-Dominguez, M., Gao, C., Gapstur, S. M., Garber, J., Garcia-Closas, M., Garcia-Saenz, J. A., Gaudet, M. M., Gayther, S. A., Belotti, M., Bertrand, O., Birot, A. -M., Buecher, B., Caputo, S., Dupre, A., Fourme, E., Gauthier-Villars, M., Golmard, L., Le Mentec, M., Moncoutier, V., de Pauw, A., Saule, C., Boutry-Kryza, N., Calender, A., Giraud, S., Leone, M., Bressac-de-Paillerets, B., Caron, O., Guillaud-Bataille, M., Bignon, Y. -J., Uhrhammer, N., Bonadona, V., Lasset, C., Berthet, P., Castera, L., Vaur, D., Bourdon, V., Nogues, C., Noguchi, T., Popovici, C., Remenieras, A., Sobol, H., Coupier, I., Pujol, P., Adenis, C., Dumont, A., Revillion, F., Muller, D., Barouk-Simonet, E., Bonnet, F., Bubien, V., Longy, M., Sevenet, N., Gladieff, L., Guimbaud, R., Feillel, V., Toulas, C., Dreyfus, H., Leroux, C. D., Peysselon, M., Rebischung, C., Legrand, C., Baurand, A., Bertolone, G., Coron, F., Faivre, L., Jacquot, C., Lizard, S., Kientz, C., Lebrun, M., Prieur, F., Fert-Ferrer, S., Mari, V., Venat-Bouvet, L., Bezieau, S., Delnatte, C., Mortemousque, I., Colas, C., Coulet, F., Soubrier, F., Warcoin, M., Bronner, M., Sokolowska, J., Collonge-Rame, M. -A., Damette, A., Gesta, P., Lallaoui, H., Chiesa, J., Molina-Gomes, D., Ingster, O., Manouvrier-Hanu, S., Lejeune, S., Giles, G. G., Glendon, G., Godwin, A. K., Goldberg, M. S., Goldgar, D. E., Guenel, P., Gutierrez-Barrera, A. M., Haeberle, L., Haiman, C. A., Hakansson, N., Hall, P., Hamann, U., Harrington, P. A., Hein, A., Heyworth, J., Hillemanns, P., Hollestelle, A., Hopper, J. L., Hosgood, H. D., Howell, A., Hu, C., Hulick, P. J., Hunter, D. J., Imyanitov, E. N., Aghmesheh, M., Greening, S., Amor, D., Gattas, M., Botes, L., Buckley, M., Friedlander, M., Koehler, J., Meiser, B., Saleh, M., Salisbury, E., Trainer, A., Tucker, K., Antill, Y., Dobrovic, A., Fellows, A., Fox, S., Harris, M., Nightingale, S., Phillips, K., Sambrook, J., Thorne, H., Armitage, S., Arnold, L., Kefford, R., Kirk, J., Rickard, E., Bastick, P., Beesley, J., Hayward, N., Spurdle, A., Walker, L., Beilby, J., Saunders, C., Bennett, I., Blackburn, A., Bogwitz, M., Gaff, C., Lindeman, G., Pachter, N., Scott, C., Sexton, A., Visvader, J., Taylor, J., Winship, I., Brennan, M., Brown, M., French, J., Edwards, S., Burgess, M., Burke, J., Patterson, B., Butow, P., Culling, B., Caldon, L., Callen, D., Chauhan, D., Eisenbruch, M., Heiniger, L., Chauhan, M., Christian, A., Dixon, J., Kidd, A., Cohen, P., Colley, A., Fenton, G., Crook, A., Dickson, R., Field, M., Cui, J., Cummings, M., Dawson, S. -J., Defazio, A., Delatycki, M., Dudding, T., Edkins, T., Farshid, G., Flanagan, J., Fong, P., Forrest, L., Gallego-Ortega, D., George, P., Gill, G., Kollias, J., Haan, E., Hart, S., Jenkins, M., Hunt, C., Lakhani, S., Lipton, L., Lobb, L., Mann, G., Mclachlan, S. A., O'Connell, S., O'Sullivan, S., Pieper, E., Robinson, B., Saunus, J., Scott, E., Shelling, A., Williams, R., Young, M. A., Isaacs, C., Jakimovska, M., Jakubowska, A., James, P., Janavicius, R., Janni, W., John, E. M., Jones, M. E., Jung, A., Kaaks, R., Karlan, B. Y., Khusnutdinova, E., Kitahara, C. M., Konstantopoulou, I., Koutros, S., Kraft, P., Lambrechts, D., Lazaro, C., Le Marchand, L., Lester, J., Lesueur, F., Lilyquist, J., Loud, J. T., K. H., Lu, Luben, R. N., Lubinski, J., Mannermaa, A., Manoochehri, M., Manoukian, S., Margolin, S., Martens, J. W. M., Maurer, T., Mavroudis, D., Mebirouk, N., Meindl, A., Menon, U., Miller, A., Montagna, M., Nathanson, K. L., Neuhausen, S. L., Newman, W. G., Nguyen-Dumont, T., Nielsen, F. C., Nielsen, S., Nikitina-Zake, L., Offit, K., Olah, E., Olopade, O. I., Olshan, A. F., Olson, J. E., Olsson, H., Osorio, A., Ottini, L., Peissel, B., Peixoto, A., Peto, J., Plaseska-Karanfilska, D., Pocza, T., Presneau, N., Pujana, M. A., Punie, K., Rack, B., Rantala, J., Rashid, M. U., Rau-Murthy, R., Rennert, G., Lejbkowicz, F., Rhenius, V., Romero, A., Rookus, M. A., Ross, E. A., Rossing, M., Rudaitis, V., Ruebner, M., Saloustros, E., Sanden, K., Santamarina, M., Scheuner, M. T., Schmutzler, R. K., Schneider, M., Senter, L., Shah, M., Sharma, P., Shu, X. -O., Simard, J., Singer, C. F., Sohn, C., Soucy, P., Southey, M. C., Spinelli, J. J., Steele, L., Stoppa-Lyonnet, D., Tapper, W. J., Teixeira, M. R., Terry, M. B., Thomassen, M., Thompson, J., Thull, D. L., Tischkowitz, M., Tollenaar, R. A. E. M., Torres, D., Troester, M. A., Truong, T., Tung, N., Untch, M., Vachon, C. M., van Rensburg, E. J., van Veen, E. M., Vega, A., Viel, A., Wappenschmidt, B., Weitzel, J. N., Wendt, C., Wieme, G., Wolk, A., Yang, X. R., Zheng, W., Ziogas, A., Zorn, K. K., Dunning, A. M., Lush, M., Wang, Q., Mcguffog, L., Parsons, M. T., Pharoah, P. D. P., Fostira, F., Toland, A. E., Andrulis, I. L., Ramus, S. J., Swerdlow, A. J., Greene, M. H., Chung, W. K., Milne, R. L., Chenevix-Trench, G., Dork, T., Schmidt, M. K., Easton, D. F., Radice, P., Hahnen, E., Antoniou, A. C., Couch, F. J., Nevanlinna, H., Surralles, J., Peterlongo, P., Caleca, Laura [0000-0002-3381-7493], Muranen, Taru A. [0000-0002-5895-1808], Dennis, Joe [0000-0003-4591-1214], Adlard, Julian [0000-0002-1693-0435], Arndt, Volker [0000-0001-9320-8684], Auber, Bernd [0000-0003-1880-291X], Bonanni, Bernardo [0000-0003-3589-2128], Brauch, Hiltrud [0000-0001-7531-2736], Devilee, Peter [0000-0002-8023-2009], Foulkes, William D. [0000-0001-7427-4651], Isaacs, Claudine [0000-0002-9646-1260], Jakimovska, Milena [0000-0002-1506-0669], Konstantopoulou, Irene [0000-0002-0470-0309], Lesueur, Fabienne [0000-0001-7404-4549], Menon, Usha [0000-0003-3708-1732], Miller, Austin [0000-0001-9739-8462], Peto, Julian [0000-0002-1685-8912], Punie, Kevin [0000-0002-1162-7963], Romero, Atocha [0000-0002-1634-7397], Saloustros, Emmanouil [0000-0002-0485-0120], Scott, Christopher [0000-0003-1340-0647], Viel, Alessandra [0000-0003-2804-0840], Wieme, Greet [0000-0003-2718-5300], Zheng, Wei [0000-0003-1226-070X], Ziogas, Argyrios [0000-0003-4529-3727], Greene, Mark H. [0000-0003-1852-9239], Nevanlinna, Heli [0000-0002-0916-2976], Peterlongo, Paolo [0000-0001-6951-6855], Apollo - University of Cambridge Repository, Medical Oncology, Department of Genetics and Microbiology, Universitat Autònoma de Barcelona (UAB), IFOM, Istituto FIRC di Oncologia Molecolare (IFOM), Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Department of Clinical Genetics, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), Yorkshire Regional Genetics Service, Department of Pathology, University Hospital and University of Iceland School of Medicine, Division of Oncology, Department of Gynaecology and Obstetrics, University Hospital Schleswig–Holstein, Università degli Studi di Milano [Milano] (UNIMI), Medical Oncology Department, Vall d'Hebron University Hospital [Barcelona], University of Iceland [Reykjavik]-Landspitali - University Hospital, Centre for Cancer Genetic Epidemiology, University of Cambridge [UK] (CAM), Leicestershire Clinical Genetics Service, University Hospitals Leicester, Occupational and Environmental Epidemiology Branch [Bethesda, Maryland], Division of Cancer Epidemiology and Genetics [Bethesda, Maryland], National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH)-National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Laboratoire Interuniversitaire des Systèmes Atmosphériques (LISA (UMR_7583)), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Departemento Genetica Humana, Centro Nacional Investigaciones Oncologicas, Chaim Sheba Medical Center, Institute of Biochemistry and Genetics of Ufa Scientific Centre, Russian Academy of Sciences [Moscow] (RAS), Department of Oncology, Department of Obstetrics and Gynaecology (MHH), Hannover Medical School [Hannover] (MHH), Division of Cancer Prevention and Genetics, Department of Oncology, Clinical Sciences, Lund University [Lund]-Skåne University Hospital, North West Thames Regional Genetics, Northwick Park Hospital, Dr. Margarete Fischer-Bosch Institute for Clinical Pharmacology [Stuttgart], Division of Clinical Epidemiology and Aging Research, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Molecular Epidemiology Research Group, Department of Internal Medicine, Huntsman Cancer Institute, Molecular Oncology Laboratory, Hospital Clínico San Carlos, Section of Genetic Oncology, University of Pisa - Università di Pisa, Department of Cancer Epidemiology, Division of Cancer Epidemiology, Division of Cancer Epidemiology and Genetics, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Genetics and Pathology, International Hereditary Cancer Centre-Pomeranian Medical University [Szczecin] (PUM), Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Division of Population Science, Fox Chase Cancer Center, Department of Human Genetics & Department of Pathology, Leiden University Medical Center (LUMC), Oncogenetics Laboratory, Vall d'Hebron Institute of Oncology (VHIO), Department of Obstetrics and Gynecology [Munich, Germany], University-Hospital Munich-Großhadern [München]-Ludwig Maximilian University [Munich] (LMU), Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], Wessex clinical genetics service, Lund University Hospital, Department of Genomic Medicine, University of Manchester [Manchester], Department of Breast Surgery, Herlev and Gentofte Hospital, Department of Human Genetics [Montréal], McGill University = Université McGill [Montréal, Canada], The Susanne Levy Gertner Oncogenetics Unit, Institute of Human Genetics, National Institutes of Health [Bethesda] (NIH), Epidemiology Research Program, American Cancer Society, Department of Preventive Medicine, University of Southern California (USC)-Keck School of Medicine [Los Angeles], University of Southern California (USC), University of Melbourne, Ontario Cancer Genetics Network, Cancer Care Ontario, Department of Pathology and Laboratory Medicine, University of Kansas Medical Center [Kansas City, KS, USA], International Agency for Cancer Research (IACR), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of OB/Gyn, University Breast Center Franconia, Univeristy Hospital Erlangen, Molecular Genetics of Breast Cancer, Centre for Cancer Genetic Epidemiology [Cambridge], University of Cambridge [UK] (CAM)-Department of Oncology, Department of Medical Oncology, Josephine Nefkens Institute and Daniel den Hoed Cancer Center, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Centre for MEGA Epidemiology, The University of Melbourne, Victoria, Australia, The Christie, Department of Statistics, Penn State University, University of Pennsylvania [Philadelphia], Laboratory of Molecular Oncology, N.N. Petrov Institute of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Department of Molecular and Regenerative Medicine, Hematology, Oncology and Transfusion, Vilnius University [Vilnius]-Hospital Santariskiu Clinics, Department of Gynecology and Obstetrics, Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Department of Epidemiology, Cancer Prevention Institute of California, Unit of Nutrition and Cancer, Women's Cancer Program, Samuel Oschin Comprehensive Cancer Institute, Institute of Biochemistry and Genetics [Bashkortostan Republic, Russia], Russian Academy of Sciences / Ufa Scientific Centre [Bashkortostan Republic, Russia]], National Center for Scientific Research 'Demokritos' (NCSR), Harvard School of Public Health, Laboratory for translational genetics Leuven, Genetic Counseling and Hereditary Cancer Programme, Catalan Institute of Oncology, University of Hawai‘i [Mānoa] (UHM), Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinical Genetics Branch, Strangeways Research Laboratory, Unit of Medical Genetics, Fondazione IRCCS INT, Department of Gynaecology and Obstetrics, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Institute for Women's Health [London], University College London Hospitals (UCLH), Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV - IRCCS, Department of Medicine, Medical Genetics, Abramson Cancer Center-Perelman School of Medicine, Department of Population Sciences, Beckman Research Institute of City of Hope, Section Génétique - Groupe Prédispositions génétiques au cancer, Centre International de Recherche contre le Cancer (CIRC), Clinical Genetics Service, Memorial Sloane Kettering Cancer Center [New York], Department of Molecular Genetics and Department of Chemotherapy, National Institute of Oncology, University of Chicago, Recherches épidémiologiques et statistiques sur l'environnement et la santé., Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Human Genetics Group, Spanish National Cancer Research Centre, Department of Molecular Medicine, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Department of Genetics, Portuguese Oncology Institute, Non-Communicable Disease Epidemiology Unit, London School of Hygiene and Tropical Medicine (LSHTM), University of Munich, Karolinska University Hospital [Stockholm], Umm Al-Qura University, Department of Community Medicine and Epidemiology, CHS National Cancer Control Center, Netherlands Cancer Institute, IT University of Copenhagen (ITU), Division of Molecular Gyneco-Oncology, Department of Gynaecology and Obstetrics, Clinical Center Un, Queen's University [Belfast] (QUB), Vanderbilt Epidemiology Center, Institute for Medicine and Public Health, Vanderbilt University School of Medicine [Nashville], Laboratoire de Génomique des Cancers, Université Laval [Québec] (ULaval), Division of Special Gynecology, Medizinische Universität Wien = Medical University of Vienna-Department of OB/GYN, Division Molecular Biology of Breast Cancer, Department of Gynecology and Obstetrics, Universität Heidelberg [Heidelberg], Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec, Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto = University of Porto, Department of Epidemiology [Columbia University], Columbia University [New York]-Columbia Mailman School of Public Health, Columbia University [New York], Odense University Hospital, Instituto de Genética Humana, Pontificia Universidad Javeriana (PUJ), HELIOS Hospital Berlin-Buch, Cancer Genetics Laboratory, University of Pretoria [South Africa], Genomic Medicine Group, Universidade de Santiago de Compostela [Spain] (USC ), Division of Experimental Oncology 1, Centro di Riferimento Oncologico (CRO), Division of Molecular Gyneco-Oncology, Department of Gynaecology and Obstetrics, City of Hope Comprehensive Cancer Center and Department of Population Sciences, Beckman Research Institute, Center for Astrophysical Sciences [Baltimore], Johns Hopkins University (JHU), European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, University of Science and Technology Beijing [Beijing] (USTB), University of Cambridge [UK] (CAM)-Department of Public Health and Primary Care-Centre for Cancer Genetic Epidemiology, Université de Pau et des Pays de l'Adour (UPPA), Department of Molecular Virology, Immunology and Medical Genetics [Colombus], Ohio State University [Columbus] (OSU)-College of Medicine and Public Health [Colombus], Departments of Molecular Genetics and Laboratory Medicine and Pathobiology, University of Toronto-Cancer Care Ontario, The institute of cancer research [London], Department of Medical Genetics, Mayo Clinic, Cancer Epidemiology Centre, Cancer Council Victoria, Queensland Institute of Medical Research, Cancer Research U.K. Genetic Epidemiology Unit, Unit of Genetic Susceptibility to Cancer, Department of Experimental Oncology and Molecular Medici, Department of Laboratory Medicine and Pathology, Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine-Fondazione IRCCS Istituto Nazionale Tumori (INT), Muranen, Taru A [0000-0002-5895-1808], Foulkes, William D [0000-0001-7427-4651], Greene, Mark H [0000-0003-1852-9239], Institut Català de la Salut, [Figlioli G, Catucci I] IFOM - the FIRC Institute for Molecular Oncology, Genome Diagnostics Program, Milan, Italy. [Bogliolo M, Pujol R] Department of Genetics and Microbiology, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain. Center for Biomedical Network Research on Rare Diseases (CIBERER), Madrid, Spain. Institute of Biomedical Research, Sant Pau Hospital, Barcelona, Spain. [Caleca L] Fondazione IRCCS Istituto Nazionale dei Tumori, Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Research, Milan, Italy. [Lasheras SV] Department of Genetics and Microbiology, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain. [Balmaña J] High Risk and Cancer Prevention Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Diez O] Oncogenetics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Genètica, Vall d’Hebron Hospital Universitari, Barcelona, Spain, Hospital Universitari Vall d'Hebron, University of Iceland [Reykjavik], Università degli Studi di Milano = University of Milan (UNIMI), Universiteit Leiden-Universiteit Leiden, University of Pennsylvania-University of Pennsylvania, University of Pennsylvania, Georgetown University [Washington] (GU), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Universität Heidelberg [Heidelberg] = Heidelberg University, European Project: 634935,H2020,H2020-PHC-2014-two-stage,BRIDGES(2015), European Project: 633784,H2020,H2020-PHC-2014-two-stage,B-CAST(2015), European Project: 223175,EC:FP7:HEALTH,FP7-HEALTH-2007-B,COGS(2009), Human Genetics, Vall d'Hebron Barcelona Hospital Campus, Autonomous University of Barcelona, Universitat Autònoma de Barcelona [Barcelona] (UAB), Università degli studi di Milano [Milano], University Hospitals of Leicester, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Department of Biology, University of Pisa, Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pomeranian Medical University-International Hereditary Cancer Centre, McGill University, University of Kansas Medical Center [Lawrence], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Oncology-University of Cambridge [UK] (CAM), Heinrich-Heine-Universität Düsseldorf [Düsseldorf], Cancer et génôme: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Technical University of Munich (TUM), Università degli Studi di Roma 'La Sapienza' [Rome], IT University of Copenhagen, Laval University [Québec], Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Pontificia Universidad Javeriana, University of Santiago de Compostela, Læknadeild (HÍ), Faculty of Medicine (UI), Biomedical Center (UI), Lífvísindasetur (HÍ), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), MINES ParisTech - École nationale supérieure des mines de Paris, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Universidade do Porto, Ministerio de Economía y Competitividad (España), Unión Europea. Comisión Europea, Against Breast Cancer, Cancer Research UK (Reino Unido), Unión Europea. Comisión Europea. H2020, Cancer UK Grant, Canadian Institutes of Health Research, Ministère de Économie, de la science et de innovation (Canadá), NIH - National Cancer Institute (NCI) (Estados Unidos), Dutch Cancer Society (Holanda), Instituto de Salud Carlos III, Xunta de Galicia (España), Canadian Cancer Society, California Breast Cancer Research Program, California Department of Public Health, Medical Research Council (Reino Unido), Free State of Saxony, Germany (LIFE -Leipzig Research Centre for Civilization Diseases), Federal Ministry of Education & Research (Alemania), German Cancer Aid, Helsinki University Central Hospital Research Fund, Finlands Akademi (Finlandia), Deutsche Forschungsgemeinschaft (Alemania), Russian Foundation for Basic Research, Ministry of Science and Higher Education (Rusia), National Health and Medical Research Council (Australia), Biobanking and BioMolecular resources Research Infrastructure (Países Bajos), Estée Lauder Companies’ Breast Cancer Campaign, Swedish Research Council, NIH - National Cancer Institute (NCI). Specialized Programs of Research Excellence (SPOREs) (Estados Unidos), Lon V. Smith Foundation, Research Coincil of Lithuania, Italian Association for Cancer Research, University of Kansas. Cancer Center (Estados Unidos), Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), French National Cancer Institute, Netherlands Organisation for Health Research and Development, Pink Ribbons Project, United States of Department of Health & Human Services, HUS Gynecology and Obstetrics, Clinicum, University of Helsinki, Medicum, Kristiina Aittomäki / Principal Investigator, HUSLAB, University Management, HUS Comprehensive Cancer Center, Biosciences, Helsinki University Hospital, and Lietuvos Mokslo Taryba (Lituania)
Subjects: 0301 basic medicine, Gene mutation, Càncer - Aspectes genètics, chemistry.chemical_compound, 0302 clinical medicine, Breast cancer, Mama - Càncer, Fanconi anemia, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Brjóstakrabbamein, Medicine and Health Sciences, Pharmacology (medical), FANCM, 631/208/68, skin and connective tissue diseases, Cancer genetics, Triple-negative breast cancer, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Manchester Cancer Research Centre, Otros calificadores::Otros calificadores::/genética [Otros calificadores], article, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, Oncology, 030220 oncology & carcinogenesis, Neoplasms::Neoplasms by Site::Breast Neoplasms::Triple Negative Breast Neoplasms [DISEASES], [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Life Sciences & Biomedicine, 3122 Cancers, ABCTB Investigators, lcsh:RC254-282, KConFab, Olaparib, Càncer de mama, GEMO Study Collaborators, 03 medical and health sciences, breast cancer, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, SDG 3 - Good Health and Well-being, 631/67/68, medicine, Other subheadings::Other subheadings::/genetics [Other subheadings], Erfðafræði, Radiology, Nuclear Medicine and imaging, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, ddc:610, Risk factor, CHEK2, Krabbamein, Cancer och onkologi, FancM, Science & Technology, cancer, MUTATIONS, business.industry, ResearchInstitutes_Networks_Beacons/mcrc, Biology and Life Sciences, nutritional and metabolic diseases, cancer genetics, medicine.disease, GENE, Expressió gènica, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, neoplasias::neoplasias por localización::neoplasias de la mama::neoplasias de mama triple negativos [ENFERMEDADES], 030104 developmental biology, chemistry, 692/4028/67/68, Cancer and Oncology, FANCONI-ANEMIA, Cancer research, gene expression, C.5791C-GREATER-THAN-T, business
Abstract: Publisher's version (útgefin grein), Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors., Peterlongo laboratory is supported by Associazione Italiana Ricerca sul Cancro (AIRC; IG2015 no.16732) to P. Peterlongo and by a fellowship from Fondazione Umberto Veronesi to G. Figlioli. Surrallés laboratory is supported by the ICREA-Academia program, the Spanish Ministry of Health (projects FANCOSTEM and FANCOLEN), the Spanish Ministry of Economy and Competiveness (projects CB06/07/0023 and RTI2018-098419-B-I00), the European Commission (EUROFANCOLEN project HEALTH-F5-2012-305421 and P-SPHERE COFUND project), the Fanconi Anemia Research Fund Inc, and the “Fondo Europeo de Desarrollo Regional, una manera de hacer Europa” (FEDER). CIBERER is an initiative of the Instituto de Salud Carlos III, Spain. BCAC: we thank all the individuals who took part in these studies and all the researchers, clinicians, technicians and administrative staff who have enabled this work to be carried out. ABCFS thank Maggie Angelakos, Judi Maskiell, Tu Nguyen-Dumont is a National Breast Cancer Foundation (Australia) Career Development Fellow. ABCS thanks the Blood bank Sanquin, The Netherlands. Samples are made available to researchers on a non-exclusive basis. BCEES thanks Allyson Thomson, Christobel Saunders, Terry Slevin, BreastScreen Western Australia, Elizabeth Wylie, Rachel Lloyd. The BCINIS study would not have been possible without the contributions of Dr. Hedy Rennert, Dr. K. Landsman, Dr. N. Gronich, Dr. A. Flugelman, Dr. W. Saliba, Dr. E. Liani, Dr. I. Cohen, Dr. S. Kalet, Dr. V. Friedman, Dr. O. Barnet of the NICCC in Haifa, and all the contributing family medicine, surgery, pathology and oncology teams in all medical institutes in Northern Israel. The BREOGAN study would not have been possible without the contributions of the following: Manuela Gago-Dominguez, Jose Esteban Castelao, Angel Carracedo, Victor Muñoz Garzón, Alejandro Novo Domínguez, Maria Elena Martinez, Sara Miranda Ponte, Carmen Redondo Marey, Maite Peña Fernández, Manuel Enguix Castelo, Maria Torres, Manuel Calaza (BREOGAN), José Antúnez, Máximo Fraga and the staff of the Department of Pathology and Biobank of the University Hospital Complex of Santiago-CHUS, Instituto de Investigación Sanitaria de Santiago, IDIS, Xerencia de Xestion Integrada de Santiago-SERGAS; Joaquín González-Carreró and the staff of the Department of Pathology and Biobank of University Hospital Complex of Vigo, Instituto de Investigacion Biomedica Galicia Sur, SERGAS, Vigo, Spain. BSUCH thanks Peter Bugert, Medical Faculty Mannheim. CBCS thanks study participants, co-investigators, collaborators and staff of the Canadian Breast Cancer Study, and project coordinators Agnes Lai and Celine Morissette. CCGP thanks Styliani Apostolaki, Anna Margiolaki, Georgios Nintos, Maria Perraki, Georgia Saloustrou, Georgia Sevastaki, Konstantinos Pompodakis. CGPS thanks staff and participants of the Copenhagen General Population Study. For the excellent technical assistance: Dorthe Uldall Andersen, Maria Birna Arnadottir, Anne Bank, Dorthe Kjeldgård Hansen. The Danish Cancer Biobank is acknowledged for providing infrastructure for the collection of blood samples for the cases. Investigators from the CPS-II cohort thank the participants and Study Management Group for their invaluable contributions to this research. They also acknowledge the contribution to this study from central cancer registries supported through the Centers for Disease Control and Prevention National Program of Cancer Registries, as well as cancer registries supported by the National Cancer Institute Surveillance Epidemiology and End Results program. The CTS Steering Committee includes Leslie Bernstein, Susan Neuhausen, James Lacey, Sophia Wang, Huiyan Ma, and Jessica Clague DeHart at the Beckman Research Institute of City of Hope, Dennis Deapen, Rich Pinder, and Eunjung Lee at the University of Southern California, Pam Horn-Ross, Peggy Reynolds, Christina Clarke Dur and David Nelson at the Cancer Prevention Institute of California, Hoda Anton-Culver, Argyrios Ziogas, and Hannah Park at the University of California Irvine, and Fred Schumacher at Case Western University. DIETCOMPLYF thanks the patients, nurses and clinical staff involved in the study. The DietCompLyf study was funded by the charity Against Breast Cancer (Registered Charity Number 1121258) and the NCRN. We thank the participants and the investigators of EPIC (European Prospective Investigation into Cancer and Nutrition). ESTHER thanks Hartwig Ziegler, Sonja Wolf, Volker Hermann, Christa Stegmaier, Katja Butterbach. FHRISK thanks NIHR for funding. GC-HBOC thanks Stefanie Engert, Heide Hellebrand, Sandra Kröber and LIFE - Leipzig Research Centre for Civilization Diseases (Markus Loeffler, Joachim Thiery, Matthias Nüchter, Ronny Baber). The GENICA Network: Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, and University of Tübingen, Germany [HB, Wing-Yee Lo], German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) [HB], Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy - EXC 2180 - 390900677 [HB], Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany [Yon-Dschun Ko, Christian Baisch], Institute of Pathology, University of Bonn, Germany [Hans-Peter Fischer], Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany [Ute Hamann], Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, Germany [TB, Beate Pesch, Sylvia Rabstein, Anne Lotz]; and Institute of Occupational Medicine and Maritime Medicine, University Medical Center Hamburg-Eppendorf, Germany [Volker Harth]. HABCS thanks Michael Bremer. HEBCS thanks Heidi Toiminen, Kristiina Aittomäki, Irja Erkkilä and Outi Malkavaara. HMBCS thanks Peter Hillemanns, Hans Christiansen and Johann H. Karstens. HUBCS thanks Shamil Gantsev. KARMA thanks the Swedish Medical Research Counsel. KBCP thanks Eija Myöhänen, Helena Kemiläinen. LMBC thanks Gilian Peuteman, Thomas Van Brussel, EvyVanderheyden and Kathleen Corthouts. MABCS thanks Milena Jakimovska (RCGEB “Georgi D. Efremov), Katerina Kubelka, Mitko Karadjozov (Adzibadem-Sistina” Hospital), Andrej Arsovski and Liljana Stojanovska (Re-Medika” Hospital) for their contributions and commitment to this study. MARIE thanks Petra Seibold, Dieter Flesch-Janys, Judith Heinz, Nadia Obi, Alina Vrieling, Sabine Behrens, Ursula Eilber, Muhabbet Celik, Til Olchers and Stefan Nickels. MBCSG (Milan Breast Cancer Study Group) thanks Daniela Zaffaroni, Irene Feroce, and the personnel of the Cogentech Cancer Genetic Test Laboratory. We thank the coordinators, the research staff and especially the MMHS participants for their continued collaboration on research studies in breast cancer. MSKCC thanks Marina Corines and Lauren Jacobs. MTLGEBCS would like to thank Martine Tranchant (CHU de Québec Research Center), Marie-France Valois, Annie Turgeon and Lea Heguy (McGill University Health Center, Royal Victoria Hospital; McGill University) for DNA extraction, sample management and skillful technical assistance. J.S. is Chairholder of the Canada Research Chair in Oncogenetics. NBHS thanks study participants and research staff for their contributions and commitment to the studies. We would like to thank the participants and staff of the Nurses’ Health Study and Nurses’ Health Study II for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. The study protocol was approved by the institutional review boards of the Brigham and Women’s Hospital and Harvard T.H. Chan School of Public Health, and those of participating registries as required. The authors assume full responsibility for analyses and interpretation of these data. OFBCR thanks Teresa Selander and Nayana Weerasooriya. ORIGO thanks E. Krol-Warmerdam, and J. Blom for patient accrual, administering questionnaires, and managing clinical information. PBCS thanks Louise Brinton, Mark Sherman, Neonila Szeszenia-Dabrowska, Beata Peplonska, Witold Zatonski, Pei Chao and Michael Stagner. The ethical approval for the POSH study is MREC /00/6/69, UKCRN ID: 1137. We thank staff in the Experimental Cancer Medicine Centre (ECMC) supported Faculty of Medicine Tissue Bank and the Faculty of Medicine DNA Banking resource. PREFACE thanks Sonja Oeser and Silke Landrith. PROCAS thanks NIHR for funding. RBCS thanks Petra Bos, Jannet Blom, Ellen Crepin, Elisabeth Huijskens, Anja Kromwijk-Nieuwlaat, Annette Heemskerk, the Erasmus MC Family Cancer Clinic. We thank the SEARCH and EPIC teams. SKKDKFZS thanks all study participants, clinicians, family doctors, researchers and technicians for their contributions and commitment to this study. We thank the SUCCESS Study teams in Munich, Duessldorf, Erlangen and Ulm. SZBCS thanks Ewa Putresza. UCIBCS thanks Irene Masunaka. UKBGS thanks Breast Cancer Now and the Institute of Cancer Research for support and funding of the Breakthrough Generations Study, and the study participants, study staff, and the doctors, nurses and other health care providers and health information sources who have contributed to the study. We acknowledge NHS funding to the Royal Marsden/ICR NIHR Biomedical Research Centre. CIMBA: we are grateful to all the families and clinicians who contribute to the studies; Sue Healey, in particular taking on the task of mutation classification with the late Olga Sinilnikova; Maggie Angelakos, Judi Maskiell, Helen Tsimiklis; members and participants in the New York site of the Breast Cancer Family Registry; members and participants in the Ontario Familial Breast Cancer Registry; Vilius Rudaitis and Laimonas Griškevičius; Yuan Chun Ding and Linda Steele for their work in participant enrollment and biospecimen and data management; Bent Ejlertsen and Anne-Marie Gerdes for the recruitment and genetic counseling of participants; Alicia Barroso, Rosario Alonso and Guillermo Pita; all the individuals and the researchers who took part in CONSIT TEAM (Consorzio Italiano Tumori Ereditari Alla Mammella), thanks in particular: Giulia Cagnoli, Roberta Villa, Irene Feroce, Mariarosaria Calvello, Riccardo Dolcetti, Giuseppe Giannini, Laura Papi, Gabriele Lorenzo Capone, Liliana Varesco, Viviana Gismondi, Maria Grazia Tibiletti, Daniela Furlan, Antonella Savarese, Aline Martayan, Stefania Tommasi, Brunella Pilato, Isabella Marchi, Elena Bandieri, Antonio Russo, Daniele Calistri and the personnel of the Cogentech Cancer Genetic Test Laboratory, Milan, Italy. FPGMX: members of the Cancer Genetics group (IDIS): Ana Blanco, Miguel Aguado, Uxía Esperón and Belinda Rodríguez. We thank all participants, clinicians, family doctors, researchers, and technicians for their contributions and commitment to the DKFZ study and the collaborating groups in Lahore, Pakistan (Noor Muhammad, Sidra Gull, Seerat Bajwa, Faiz Ali Khan, Humaira Naeemi, Saima Faisal, Asif Loya, Mohammed Aasim Yusuf) and Bogota, Colombia (Diana Torres, Ignacio Briceno, Fabian Gil). Genetic Modifiers of Cancer Risk in BRCA1/2 Mutation Carriers (GEMO) study is a study from the National Cancer Genetics Network UNICANCER Genetic Group, France. We wish to pay a tribute to Olga M. Sinilnikova, who with Dominique Stoppa-Lyonnet initiated and coordinated GEMO until she sadly passed away on the 30th June 2014. The team in Lyon (Olga Sinilnikova, Mélanie Léoné, Laure Barjhoux, Carole Verny-Pierre, Sylvie Mazoyer, Francesca Damiola, Valérie Sornin) managed the GEMO samples until the biological resource centre was transferred to Paris in December 2015 (Noura Mebirouk, Fabienne Lesueur, Dominique Stoppa-Lyonnet). We want to thank all the GEMO collaborating groups for their contribution to this study. Drs.Sofia Khan, Irja Erkkilä and Virpi Palola; The Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON) consists of the following Collaborating Centers: Netherlands Cancer Institute (coordinating center), Amsterdam, NL: M.A. Rookus, F.B.L. Hogervorst, F.E. van Leeuwen, M.A. Adank, M.K. Schmidt, N.S. Russell, D.J. Jenner; Erasmus Medical Center, Rotterdam, NL: J.M. Collée, A.M.W. van den Ouweland, M.J. Hooning, C.M. Seynaeve, C.H.M. van Deurzen, I.M. Obdeijn; Leiden University Medical Center, NL: C.J. van Asperen, P. Devilee, T.C.T.E.F. van Cronenburg; Radboud University Nijmegen Medical Center, NL: C.M. Kets, A.R. Mensenkamp; University Medical Center Utrecht, NL: M.G.E.M. Ausems, M.J. Koudijs; Amsterdam Medical Center, NL: C.M. Aalfs, H.E.J. Meijers-Heijboer; VU University Medical Center, Amsterdam, NL: K. van Engelen, J.J.P. Gille; Maastricht University Medical Center, NL: E.B. Gómez-Garcia, M.J. Blok; University of Groningen, NL: J.C. Oosterwijk, A.H. van der Hout, M.J. Mourits, G.H. de Bock; The Netherlands Comprehensive Cancer Organisation (IKNL): S. Siesling, J.Verloop; The nationwide network and registry of histo- and cytopathology in The Netherlands (PALGA): A.W. van den Belt-Dusebout. HEBON thanks the study participants and the registration teams of IKNL and PALGA for part of the data collection. Overbeek; the Hungarian Breast and Ovarian Cancer Study Group members (Janos Papp, Aniko Bozsik, Zoltan Matrai, Miklos Kasler, Judit Franko, Maria Balogh, Gabriella Domokos, Judit Ferenczi, Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary) and the clinicians and patients for their contributions to this study; HVH (University Hospital Vall d’Hebron) the authors acknowledge the Oncogenetics Group (VHIO) and the High Risk and Cancer Prevention Unit of the University Hospital Vall d’Hebron, Miguel Servet Progam (CP10/00617), and the Cellex Foundation for providing research facilities and equipment; the ICO Hereditary Cancer Program team led by Dr. Gabriel Capella; the ICO Hereditary Cancer Program team led by Dr. Gabriel Capella; Dr Martine Dumont for sample management and skillful assistance; Catarina Santos and Pedro Pinto; members of the Center of Molecular Diagnosis, Oncogenetics Department and Molecular Oncology Research Center of Barretos Cancer Hospital; Heather Thorne, Eveline Niedermayr, all the kConFab investigators, research nurses and staff, the heads and staff of the Family Cancer Clinics, and the Clinical Follow Up Study (which has received funding from the NHMRC, the National Breast Cancer Foundation, Cancer Australia, and the National Institute of Health (USA)) for their contributions to this resource, and the many families who contribute to kConFab; the investigators of the Australia New Zealand NRG Oncology group; members and participants in the Ontario Cancer Genetics Network; Kevin Sweet, Caroline Craven, Julia Cooper, Amber Aielts, and Michelle O’Conor; Christina Selkirk; Helena Jernström, Karin Henriksson, Katja Harbst, Maria Soller, Ulf Kristoffersson; from Gothenburg Sahlgrenska University Hospital: Anna Öfverholm, Margareta Nordling, Per Karlsson, Zakaria Einbeigi; from Stockholm and Karolinska University Hospital: Anna von Wachenfeldt, Annelie Liljegren, Annika Lindblom, Brita Arver, Gisela Barbany Bustinza; from Umeå University Hospital: Beatrice Melin, Christina Edwinsdotter Ardnor, Monica Emanuelsson; from Uppsala University: Hans Ehrencrona, Maritta Hellström Pigg, Richard Rosenquist; from Linköping University Hospital: Marie Stenmark-Askmalm, Sigrun Liedgren; Cecilia Zvocec, Qun Niu; Joyce Seldon and Lorna Kwan; Dr. Robert Nussbaum, Beth Crawford, Kate Loranger, Julie Mak, Nicola Stewart, Robin Lee, Amie Blanco and Peggy Conrad and Salina Chan; Carole Pye, Patricia Harrington and Eva Wozniak. OSUCCG thanks Kevin Sweet, Caroline Craven, Julia Cooper, Michelle O’Conor and Amber Aeilts. BCAC is funded by Cancer Research UK [C1287/A16563, C1287/A10118], the European Union’s Horizon 2020 Research and Innovation Programme (grant numbers 634935 and 633784 for BRIDGES and B-CAST respectively), and by the European Community´s Seventh Framework Programme under grant agreement number 223175 (grant number HEALTH-F2-2009-223175) (COGS). The EU Horizon 2020 Research and Innovation Programme funding source had no role in study design, data collection, data analysis, data interpretation or writing of the report. Genotyping of the OncoArray was funded by the NIH Grant U19 CA148065, and Cancer UK Grant C1287/A16563 and the PERSPECTIVE project supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research (grant GPH-129344) and, the Ministère de l’Économie, Science et Innovation du Québec through Genome Québec and the PSRSIIRI-701 grant, and the Quebec Breast Cancer Foundation. The Australian Breast Cancer Family Study (ABCFS) was supported by grant UM1 CA164920 from the National Cancer Institute (USA). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the USA Government or the BCFR. The ABCFS was also supported by the National Health and Medical Research Council of Australia, the New South Wales Cancer Council, the Victorian Health Promotion Foundation (Australia) and the Victorian Breast Cancer Research Consortium. J.L.H. is a National Health and Medical Research Council (NHMRC) Senior Principal Research Fellow. M.C.S. is a NHMRC Senior Research Fellow. The ABCS study was supported by the Dutch Cancer Society [grants NKI 2007-3839; 2009 4363]. The Australian Breast Cancer Tissue Bank (ABCTB) was supported by the National Health and Medical Research Council of Australia, The Cancer Institute NSW and the National Breast Cancer Foundation. The AHS study is supported by the intramural research program of the National Institutes of Health, the National Cancer Institute (grant number Z01-CP010119), and the National Institute of Environmental Health Sciences (grant number Z01-ES049030). The work of the BBCC was partly funded by ELAN-Fond of the University Hospital of Erlangen. The BBCS is funded by Cancer Research UK and Breast Cancer Now and acknowledges NHS funding to the NIHR Biomedical Research Centre, and the National Cancer Research Network (NCRN). The BCEES was funded by the National Health and Medical Research Council, Australia and the Cancer Council Western Australia. For the BCFR-NY, BCFR-PA, BCFR-UT this work was supported by grant UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR. BCINIS study was funded by the BCRF (The Breast Cancer Research Foundation, USA). The BREast Oncology GAlician Network (BREOGAN) is funded by Acción Estratégica de Salud del Instituto de Salud Carlos III FIS PI12/02125/Cofinanciado FEDER; Acción Estratégica de Salud del Instituto de Salud Carlos III FIS Intrasalud (PI13/01136); Programa Grupos Emergentes, Cancer Genetics Unit, Instituto de Investigacion Biomedica Galicia Sur. Xerencia de Xestion Integrada de Vigo-SERGAS, Instituto de Salud Carlos III, Spain; Grant 10CSA012E, Consellería de Industria Programa Sectorial de Investigación Aplicada, PEME I + D e I + D Suma del Plan Gallego de Investigación, Desarrollo e Innovación Tecnológica de la Consellería de Industria de la Xunta de Galicia, Spain; Grant EC11-192. Fomento de la Investigación Clínica Independiente, Ministerio de Sanidad, Servicios Sociales e Igualdad, Spain; and Grant FEDER-Innterconecta. Ministerio de Economia y Competitividad, Xunta de Galicia, Spain. The BSUCH study was supported by the Dietmar-Hopp Foundation, the Helmholtz Society and the German Cancer Research Center (DKFZ). Sample collection and processing was funded in part by grants from the National Cancer Institute (NCI R01CA120120 and K24CA169004). CBCS is funded by the Canadian Cancer Society (grant # 313404) and the Canadian Institutes of Health Research. CCGP is supported by funding from the University of Crete. The CECILE study was supported by Fondation de France, Institut National du Cancer (INCa), Ligue Nationale contre le Cancer, Agence Nationale de Sécurité Sanitaire, de l’Alimentation, de l’Environnement et du Travail (ANSES), Agence Nationale de la Recherche (ANR). The CGPS was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council, and Herlev and Gentofte Hospital. The American Cancer Society funds the creation, maintenance, and updating of the CPS-II cohort. The CTS was initially supported by the California Breast Cancer Act of 1993 and the California Breast Cancer Research Fund (contract 97-10500) and is currently funded through the National Institutes of Health (R01 CA77398, K05 CA136967, UM1 CA164917, and U01 CA199277). Collection of cancer incidence data was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885. The University of Westminster curates the DietCompLyf database funded by Against Breast Cancer Registered Charity No. 1121258 and the NCRN. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by: Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF) (Germany); the Hellenic Health Foundation, the Stavros Niarchos Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom). The ESTHER study was supported by a grant from the Baden Württemberg Ministry of Science, Research and Arts. Additional cases were recruited in the context of the VERDI study, which was supported by a grant from the German Cancer Aid (Deutsche Krebshilfe). FHRISK is funded from NIHR grant PGfAR 0707-10031. The GC-HBOC (German Consortium of Hereditary Breast and Ovarian Cancer) is supported by the German Cancer Aid (grant no 110837, coordinator: Rita K. Schmutzler, Cologne). This work was also funded by the European Regional Development Fund and Free State of Saxony, Germany (LIFE - Leipzig Research Centre for Civilization Diseases, project numbers 713-241202, 713-241202, 14505/2470, 14575/2470). The GENICA was funded by the Federal Ministry of Education and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0 and 01KW0114, the Robert Bosch Foundation, Stuttgart, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, the Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, as well as the Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany. The GEPARSIXTO study was conducted by the German Breast Group GmbH. The GESBC was supported by the Deutsche Krebshilfe e. V. [70492] and the German Cancer Research Center (DKFZ). The HABCS study was supported by the Claudia von Schilling Foundation for Breast Cancer Research, by the Lower Saxonian Cancer Society, and by the Rudolf Bartling Foundation. The HEBCS was financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society, and the Sigrid Juselius Foundation. The HMBCS was supported by a grant from the German Research Foundation (Do 761/10-1). The HUBCS was supported by a grant from the German Federal Ministry of Research and Education (RUS08/017), and by the Russian Foundation for Basic Research and the Federal Agency for Scientific Organizations for support the Bioresource collections and RFBR grants 14-04-97088, 17-29-06014 and 17-44-020498. E.K was supported by the program for support the bioresource collections №007-030164/2 and study was performed as part of the assignment of the Ministry of Science and Higher Education of Russian Federation (№АААА-А16-116020350032-1). Financial support for KARBAC was provided through the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet, the Swedish Cancer Society, The Gustav V Jubilee foundation and Bert von Kantzows foundation. The KARMA study was supported by Märit and Hans Rausings Initiative Against Breast Cancer. The KBCP was financially supported by the special Government Funding (EVO) of Kuopio University Hospital grants, Cancer Fund of North Savo, the Finnish Cancer Organizations, and by the strategic funding of the University of Eastern Finland. LMBC is supported by the ‘Stichting tegen Kanker’. DL is supported by the FWO. The MABCS study is funded by the Research Centre for Genetic Engineering and Biotechnology “Georgi D. Efremov” and supported by the German Academic Exchange Program, DAAD. The MARIE study was supported by the Deutsche Krebshilfe e.V. [70-2892-BR I, 106332, 108253, 108419, 110826, 110828], the Hamburg Cancer Society, the German Cancer Research Center (DKFZ) and the Federal Ministry of Education and Research (BMBF) Germany [01KH0402]. MBCSG is supported by grants from the Italian Association for Cancer Research (AIRC) and by funds from the Italian citizens who allocated the 5/1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects “5 × 1000”). The MCBCS was supported by the NIH grants CA192393, CA116167, CA176785 an NIH Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201], and the Breast Cancer Research Foundation and a generous gift from the David F. and Margaret T. Grohne Family Foundation. MCCS cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC grants 209057 and 396414, and by infrastructure provided by Cancer Council Victoria. Cases and their vital status were ascertained through the Victorian Cancer Registry (VCR) and the Australian Institute of Health and Welfare (AIHW), including the National Death Index and the Australian Cancer Database. The MEC was support by NIH grants CA63464, CA54281, CA098758, CA132839 and CA164973. The MISS study is supported by funding from ERC-2011-294576 Advanced grant, Swedish Cancer Society, Swedish Research Council, Local hospital funds, Berta Kamprad Foundation, Gunnar Nilsson. The MMHS study was supported by NIH grants CA97396, CA128931, CA116201, CA140286 and CA177150. MSKCC is supported by grants from the Breast Cancer Research Foundation and Robert and Kate Niehaus Clinical Cancer Genetics Initiative. The work of MTLGEBCS was supported by the Quebec Breast Cancer Foundation, the Canadian Institutes of Health Research for the “CIHR Team in Familial Risks of Breast Cancer” program – grant # CRN-87521 and the Ministry of Economic Development, Innovation and Export Trade – grant # PSR-SIIRI-701. The NBHS was supported by NIH grant R01CA100374. Biological sample preparation was conducted the Survey and Biospecimen Shared Resource, which is supported by P30 CA68485. The Northern California Breast Cancer Family Registry (NC-BCFR) and Ontario Familial Breast Cancer Registry (OFBCR) were supported by grant UM1 CA164920 from the National Cancer Institute (USA). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the USA Government or the BCFR. The Carolina Breast Cancer Study was funded by Komen Foundation, the National Cancer Institute (P50 CA058223, U54 CA156733, U01 CA179715), and the North Carolina University Cancer Research Fund. The NHS was supported by NIH grants P01 CA87969, UM1 CA186107, and U19 CA148065. The NHS2 was supported by NIH grants UM1 CA176726 and U19 CA148065. The ORIGO study was supported by the Dutch Cancer Society (RUL 1997-1505) and the Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL CP16). The PBCS was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. Genotyping for PLCO was supported by the Intramural Research Program of the National Institutes of Health, NCI, Division of Cancer Epidemiology and Genetics. The PLCO is supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, National Institutes of Health. The POSH study is funded by Cancer Research UK (grants C1275/A11699, C1275/C22524, C1275/A19187, C1275/A15956 and Breast Cancer Campaign 2010PR62, 2013PR044. PROCAS is funded from NIHR grant PGfAR 0707-10031. The RBCS was funded by the Dutch Cancer Society (DDHK 2004-3124, DDHK 2009-4318). SEARCH is funded by Cancer Research UK [C490/A10124, C490/A16561] and supported by the UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge. The University of Cambridge has received salary support for PDPP from the NHS in the East of England through the Clinical Academic Reserve. The Sister Study (SISTER) is supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES044005 and Z01-ES049033). The Two Sister Study (2SISTER) was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES044005 and Z01-ES102245), and, also by a grant from Susan G. Komen for the Cure, grant FAS0703856. SKKDKFZS is supported by the DKFZ. The SMC is funded by the Swedish Cancer Foundation and the Swedish Research Council [grant 2017-00644 for the Swedish Infrastructure for Medical Population-based Life-course Environmental Research (SIMPLER)]. The SZBCS is financially supported under the program of Minister of Science and Higher Education “Regional Initiative of Excellence” in years 2019-2022, Grant No 002/RID/2018/19. The TNBCC was supported by: a Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a grant from the Breast Cancer Research Foundation, a generous gift from the David F. and Margaret T. Grohne Family Foundation. The UCIBCS component of this research was supported by the NIH [CA58860, CA92044] and the Lon V Smith Foundation [LVS39420]. The UKBGS is funded by Breast Cancer Now and the Institute of Cancer Research (ICR), London. ICR acknowledges NHS funding to the NIHR Biomedical Research Centre. The UKOPS study was funded by The Eve Appeal (The Oak Foundation) and supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. The USRT Study was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. CIMBA CIMBA: The CIMBA data management and data analysis were supported by Cancer Research – UK grants C12292/A20861, C12292/A11174. ACA is a Cancer Research -UK Senior Cancer Research Fellow. GCT and ABS are NHMRC Research Fellows. The PERSPECTIVE project was supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the Ministry of Economy, Science and Innovation through Genome Québec, and The Quebec Breast Cancer Foundation. BCFR: UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR. BFBOCC: Lithuania (BFBOCC-LT): Research Council of Lithuania grant SEN-18/2015 and Nr. P-MIP-19-164. BIDMC: Breast Cancer Research Foundation. BMBSA: Cancer Association of South Africa (PI Elizabeth J. van Rensburg). CNIO: Spanish Ministry of Health PI16/00440 supported by FEDER funds, the Spanish Ministry of Economy and Competitiveness (MINECO) SAF2014-57680-R and the Spanish Research Network on Rare diseases (CIBERER). COH-CCGCRN: Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under grant number R25CA112486, and RC4CA153828 (PI: J. Weitzel) from the National Cancer Institute and the Office of the Director, National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. CONSIT TEAM: Associazione Italiana Ricerca sul Cancro (AIRC; IG2014 no.15547) to P. Radice. Funds from Italian citizens who allocated the 5 × 1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects ‘5 × 1000’) to S. Manoukian. UNIROMA1: Italian Association for Cancer Research (AIRC; grant no. 21389) to L. Ottini. DFKZ: German Cancer Research Center. EMBRACE: Cancer Research UK Grants C1287/A10118 and C1287/A11990. D. Gareth Evans and Fiona Lalloo are supported by an NIHR grant to the Biomedical Research Centre, Manchester (IS-BRC-1215-20007). The Investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Ros Eeles and Elizabeth Bancroft are supported by Cancer Research UK Grant C5047/A8385. Ros Eeles is also supported by NIHR support to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. FCCC: NIH/NCI grant P30-CA006927. The University of Kansas Cancer Center (P30 CA168524) and the Kansas Bioscience Authority Eminent Scholar Program. A.K.G. was funded by R0 1CA140323, R01 CA214545, and by the Chancellors Distinguished Chair in Biomedical Sciences Professorship. Ana Vega is supported by the Spanish Health Research Foundation, Instituto de Salud Carlos III (ISCIII), partially supported by FEDER funds through Research Activity Intensification Program (contract grant numbers: INT15/00070, INT16/00154, INT17/00133), and through Centro de Investigación Biomédica en Red de Enferemdades Raras CIBERER (ACCI 2016: ER17P1AC7112/2018); Autonomous Government of Galicia (Consolidation and structuring program: IN607B), and by the Fundación Mutua Madrileña (call 2018). GC-HBOC: German Cancer Aid (grant no 110837, Rita K. Schmutzler) and the European Regional Development Fund and Free State of Saxony, Germany (LIFE - Leipzig Research Centre for Civilization Diseases, project numbers 713-241202, 713-241202, 14505/2470, 14575/2470). GEMO: Ligue Nationale Contre le Cancer; the Association “Le cancer du sein, parlons-en!” Award, the Canadian Institutes of Health Research for the “CIHR Team in Familial Risks of Breast Cancer” program, the French National Institute of Cancer (INCa) (grants AOR 01 082, 2013-1-BCB-01-ICH-1 and SHS-E-SP 18-015) and the Fondation ARC pour la recherche sur le cancer (grant PJA 20151203365). GEORGETOWN: the Survey, Recruitment and Biospecimen Shared Resource at Georgetown University (NIH/NCI grant P30-CA051008) and the Fisher Center for Hereditary Cancer and Clinical Genomics Research. HCSC: Spanish Ministry of Health PI15/00059, PI16/01292, and CB-161200301 CIBERONC from ISCIII (Spain), partially supported by European Regional Development FEDER funds. HEBCS: Helsinki University Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society and the Sigrid Juselius Foundation. HEBON: the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the Netherlands Organization of Scientific Research grant NWO 91109024, the Pink Ribbon grants 110005 and 2014-187.WO76, the BBMRI grant NWO 184.021.007/CP46 and the Transcan grant JTC 2012 Cancer 12-054. HUNBOCS: Hungarian Research Grants KTIA-OTKA CK-80745 and NKFI_OTKA K-112228. HVH (University Hospital Vall d’Hebron) This work was supported by Spanish Instituto de Salud Carlos III (ISCIII) funding, an initiative of the Spanish Ministry of Economy and Innovation partially supported by European Regional Development FEDER Funds: FIS PI12/02585 and PI15/00355. ICO: The authors would like to particularly acknowledge the support of the Asociación Española Contra el Cáncer (AECC), the Instituto de Salud Carlos III (organismo adscrito al Ministerio de Economía y Competitividad) and “Fondo Europeo de Desarrollo Regional (FEDER), una manera de hacer Europa” (PI10/01422, PI13/00285, PIE13/00022, PI15/00854, PI16/00563, P18/01029, and CIBERONC) and the Institut Català de la Salut and Autonomous Government of Catalonia (2009SGR290, 2014SGR338, 2017SGR449, and PERIS Project MedPerCan), and CERCA program. IHCC: PBZ_KBN_122/P05/2004. ILUH: Icelandic Association “Walking for Breast Cancer Research” and by the Landspitali University Hospital Research Fund. INHERIT: Canadian Institutes of Health Research for the “CIHR Team in Familial Risks of Breast Cancer” program – grant # CRN-87521 and the Ministry of Economic Development, Innovation and Export Trade – grant # PSR-SIIRI-701. IOVHBOCS: Ministero della Salute and “5 × 1000” Istituto Oncologico Veneto grant. IPOBCS: Liga Portuguesa Contra o Cancro. kConFab: The National Breast Cancer Foundation, and previously by the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. MAYO: NIH grants CA116167, CA192393 and CA176785, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), and a grant from the Breast Cancer Research Foundation. MCGILL: Jewish General Hospital Weekend to End Breast Cancer, Quebec Ministry of Economic Development, Innovation and Export Trade. Marc Tischkowitz is supported by the funded by the European Union Seventh Framework Program (2007Y2013)/European Research Council (Grant No. 310018). MSKCC: the Breast Cancer Research Foundation, the Robert and Kate Niehaus Clinical Cancer Genetics Initiative, the Andrew Sabin Research Fund and a Cancer Center Support Grant/Core Grant (P30 CA008748). NCI: the Intramural Research Program of the US National Cancer Institute, NIH, and by support services contracts NO2-CP-11019-50, N02-CP-21013-63 and N02-CP-65504 with Westat, Inc, Rockville, MD. NNPIO: the Russian Foundation for Basic Research (grants 17-54-12007, 17-00-00171 and 18-515-45012). NRG Oncology: U10 CA180868, NRG SDMC grant U10 CA180822, NRG Administrative Office and the NRG Tissue Bank (CA 27469), the NRG Statistical and Data Center (CA 37517) and the Intramural Research Program, NCI. OSUCCG: was funded by the Ohio State University Comprehensive Cancer Center. PBCS: Italian Association of Cancer Research (AIRC) [IG 2013 N.14477] and Tuscany Institute for Tumors (ITT) grant 2014-2015-2016. SMC: the Israeli Cancer Association. SWE-BRCA: the Swedish Cancer Society. UCHICAGO: NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA125183), R01 CA142996, 1U01CA161032 and by the Ralph and Marion Falk Medical Research Trust, the Entertainment Industry Fund National Women’s Cancer Research Alliance and the Breast Cancer research Foundation. UCSF: UCSF Cancer Risk Program and Helen Diller Family Comprehensive Cancer Center. UKFOCR: Cancer Researc h UK. UPENN: National Institutes of Health (NIH) (R01-CA102776 and R01-CA083855; Breast Cancer Research Foundation; Susan G. Komen Foundation for the cure, Basser Research Center for BRCA. UPITT/MWH: Hackers for Hope Pittsburgh. VFCTG: Victorian Cancer Agency, Cancer Australia, National Breast Cancer Foundation. WCP: Dr Karlan is funded by the American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN) and the National Center for Advancing Translational Sciences (NCATS), Grant UL1TR000124.
Published: 2019

28. Development and validation of circulating CA125 prediction models in postmenopausal women

Author: J. Ramón Quirós, N. Charlotte Onland-Moret, Anna Karakatsani, Marina Kvaskoff, Raina N. Fichorova, Pilar Amiano, Eva Lundin, Louise Hansen, Kathryn L. Terry, Sara Grioni, Kay-Tee Khaw, Leila Lujan-Barroso, Amalia Mattiello, Renée T. Fortner, Agnès Fournier, Linda J. Titus, Rudolf Kaaks, Sandra Colorado-Yohar, Anne Tjønneland, Timothy J. Key, Marc J. Gunter, Aurelio Barricarte, Shelley S. Tworoger, Laure Dossus, Britton Trabert, Naoko Sasamoto, Inger T. Gram, David C. Muller, Hanna Sartor, Bernard Rosner, Allison F. Vitonis, Francesca Mancini, Eleni Peppa, Valentina Fiano, María José Sánchez, Heiner Boeing, Daniel W. Cramer, Ana Babic, Hidemi S. Yamamoto, Rosario Tumino, Nicolas Wentzensen, Domenico Palli, Annika Idahl, Elisabete Weiderpass, Antonia Trichopoulou, Elio Riboli, Sasamoto, Naoko [0000-0002-4526-2181], Tjønneland, Anne [0000-0003-4385-2097], Tumino, Rosario [0000-0003-2666-414X], Apollo - University of Cambridge Repository, [Sasamoto,N, Vitonis,AF, Cramer,DW, Terry,KL] Obstetrics and Gynecology Epidemiology Center, Brigham and Women’s Hospital and Harvard Medical School, 221 Longwood Avenue, Boston, MA, USA. [Babic,A] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. [Rosner,BA] Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA. [Fortner,RT, Kaaks,R] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Yamamoto,H, Fichorova,RN] Laboratory of Genital Tract Biology, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women’s Hospital, Boston, MA, USA.[Titus,LJ] Departments of Epidemiology and Pediatrics, Geisel School of Medicine at Dartmouth and Norris Cotton Cancer Center, Hanover, NH, USA. [Tjønneland,A, Hansen,L] Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark. [Tjønneland,A] Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. [Kvaskoff,M, Fournier,A, Mancini,FR] CESP, Fac. de médecine - Univ. Paris-Sud, Fac. de médecine - UVSQ, INSERM, Université Paris-Saclay, Villejuif, France. [Kvaskoff,M, Mancini,FR] Gustave Roussy, Villejuif, France. [Boeing,H] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. [Trichopoulou,A, Peppa,E, Karakatsani,A] Hellenic Health Foundation, Athens, Greece. [Trichopoulou,A] WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Dept. of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. [Karakatsani,A] 2nd Pulmonary Medicine Department, School of Medicine, 'ATTIKON' University Hospital, National and Kapodistrian University of Athens, Haidari, Greece. [Palli,D] Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network - ISPRO, Florence, Italy. [Grioni,S] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milano, Italy. [Mattiello,A] Dipartimento Di Medicina Clinica E Chirurgia, Federico II University, Naples, Italy. [Tumino,R] Cancer Registry and Histopathology Department, 'Civic - M.P. Arezzo'Hospital, ASP, Ragusa, Italy. [Fiano,V] Unit of Cancer Epidemiology– CeRMS, Department of Medical Sciences, University of Turin, Turin, Italy. [Onland-Moret,NC] Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands. [Weiderpass,E, Gunter,M, Dossus,L] International Agency for Research on Cancer, Lyon, France. [Gram,IT] Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway. [Quirós,JR] Public Health Directorate, Asturias, Spain. [Lujan-Barroso,L] Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO-IDIBELL), L’ Hospitalet de Llobregat, Barcelona, Spain. [Sánchez,MJ] Andalusian School of Public Health (EASP), Granada, Spain. [Sánchez,MJ] Instituto de Investigación Biosanitaria de Granada (ibs. GRANADA). Universidad de Granada, Granada, Spain. [Sánchez,MJ, Colorado-Yohar,S, Barricarte,A, Amiano,P] CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain. [Colorado-Yohar,S] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Colorado-Yohar,S] Research Group on Demography and Health, National Faculty of Public Health, University of Antioquia, Medellín, Colombia. [Barricarte,A] Navarra Public Health Institute, Navarra Institute for Health Research (IdiSNA), Pamplona, Spain. [Amiano,P] Public Health Division of Gipuzkoa, BioDonostia Research Institute, San Sebastian, Spain. [Idahl,A] Department of Clinical Sciences, Obstetrics and Gynecology, Umeå University, Umeå, Sweden. [Lundin,E] Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden. [Sartor,H] Department of Medical Imaging and Physiology, Skåne University Hospital, Lund, Sweden. [Sartor,H] Department of Translational Medicine, Lund University, Lund, Sweden. [Khaw,KT] Cancer Epidemiology Unit, University of Cambridge, Cambridge, UK. [Key,TJ] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. [Muller,D, Riboli,E] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Trabert,B, Wentzensen,N] Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Washington, D.C, USA. [Tworoger,SS] Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida, USA. [Tworoger,SS, Terry,KL] Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA., Research reported in this publication was supported by U.S. National Institutes of Health under the following award numbers: R01 CA193965 (to K.L. Terry), R01 CA 158119 and R35 CA197605 (to D.W. Cramer), P01 CA087969 (to S.S. Tworoger), UM1 CA186107, R01 CA49449, UM1 CA176726, R01 CA67262, and supported in part by the intramural research program of the U.S. National Cancer Institute, National Institutes of Health, Department of Health and Human Services. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway), Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten, The Cancer Research Foundation of Northern Sweden (Sweden), Cancer Research UK (14136 to EPIC-Norfolk, and C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom).
Subjects: Antígeno Ca-125, Oncology, endocrine system diseases, medicine.medical_treatment, Càncer d'ovari, Ovarian neoplasms, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical [Medical Subject Headings], 0302 clinical medicine, Neoplasms, PROSTATE, 030212 general & internal medicine, CA-125, Early Detection of Cancer, Persons::Persons::Age Groups::Adult::Aged [Medical Subject Headings], 2. Zero hunger, RISK, Reproductive Biology, Biochemical markers, Obstetrics and Gynecology, Early detection, Diseases::Neoplasms [Medical Subject Headings], Middle Aged, Early diagnosis, female genital diseases and pregnancy complications, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Menopause, Postmenopause, Posmenopausia, 030220 oncology & carcinogenesis, Marcadors bioquímics, Biomarker (medicine), Female, Postmenopausal, Life Sciences & Biomedicine, Menopausa, medicine.medical_specialty, Neoplasias ováricas, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Early Diagnosis::Early Detection of Cancer [Medical Subject Headings], BIOMARKERS, CA125, Ovarian cancer, Prediction model, Reproduktionsmedicin och gynekologi, lcsh:Gynecology and obstetrics, Chemicals and Drugs::Biological Factors::Antigens::Antigens, Neoplasm::Antigens, Tumor-Associated, Carbohydrate::CA-125 Antigen [Medical Subject Headings], OVARIAN-CANCER, 03 medical and health sciences, Diagnóstico precoz, Internal medicine, Obstetrics, Gynecology and Reproductive Medicine, medicine, Journal Article, Humans, VDP::Medisinske Fag: 700, Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Reproductive Physiological Processes::Sexual Development::Climacteric::Menopause::Postmenopause [Medical Subject Headings], lcsh:RG1-991, Aged, Hysterectomy, Science & Technology, business.industry, Research, Case-control study, CANCER SCREENING TRIAL, Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Stepwise regression, Models, Theoretical, medicine.disease, VDP::Medical disciplines: 700, Detección precoz del cáncer, Check Tags::Female [Medical Subject Headings], CA-125 Antigen, Hormone therapy, business, Body mass index, LUNG
Abstract: Background Cancer Antigen 125 (CA125) is currently the best available ovarian cancer screening biomarker. However, CA125 has been limited by low sensitivity and specificity in part due to normal variation between individuals. Personal characteristics that influence CA125 could be used to improve its performance as screening biomarker. Methods We developed and validated linear and dichotomous (≥35 U/mL) circulating CA125 prediction models in postmenopausal women without ovarian cancer who participated in one of five large population-based studies: Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO, n = 26,981), European Prospective Investigation into Cancer and Nutrition (EPIC, n = 861), the Nurses’ Health Studies (NHS/NHSII, n = 81), and the New England Case Control Study (NEC, n = 923). The prediction models were developed using stepwise regression in PLCO and validated in EPIC, NHS/NHSII and NEC. Result The linear CA125 prediction model, which included age, race, body mass index (BMI), smoking status and duration, parity, hysterectomy, age at menopause, and duration of hormone therapy (HT), explained 5% of the total variance of CA125. The correlation between measured and predicted CA125 was comparable in PLCO testing dataset (r = 0.18) and external validation datasets (r = 0.14). The dichotomous CA125 prediction model included age, race, BMI, smoking status and duration, hysterectomy, time since menopause, and duration of HT with AUC of 0.64 in PLCO and 0.80 in validation dataset. Conclusions The linear prediction model explained a small portion of the total variability of CA125, suggesting the need to identify novel predictors of CA125. The dichotomous prediction model showed moderate discriminatory performance which validated well in independent dataset. Our dichotomous model could be valuable in identifying healthy women who may have elevated CA125 levels, which may contribute to reducing false positive tests using CA125 as screening biomarker.
Published: 2019

29. Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders

Author: Symen Ligthart, Ahmad Vaez, Urmo Võsa, Maria G. Stathopoulou, Paul S. de Vries, Bram P. Prins, Peter J. Van der Most, Toshiko Tanaka, Elnaz Naderi, Lynda M. Rose, Ying Wu, Robert Karlsson, Maja Barbalic, Honghuang Lin, René Pool, Gu Zhu, Aurélien Macé, Carlo Sidore, Stella Trompet, Massimo Mangino, Maria Sabater-Lleal, John P. Kemp, Ali Abbasi, Tim Kacprowski, Niek Verweij, Albert V. Smith, Tao Huang, Carola Marzi, Mary F. Feitosa, Kurt K. Lohman, Marcus E. Kleber, Yuri Milaneschi, Christian Mueller, Mahmudul Huq, Efthymia Vlachopoulou, Leo-Pekka Lyytikäinen, Christopher Oldmeadow, Joris Deelen, Markus Perola, Jing Hua Zhao, Bjarke Feenstra, Marzyeh Amini, Jari Lahti, Katharina E. Schraut, Myriam Fornage, Bhoom Suktitipat, Wei-Min Chen, Xiaohui Li, Teresa Nutile, Giovanni Malerba, Jian’an Luan, Tom Bak, Nicholas Schork, Fabiola Del Greco M., Elisabeth Thiering, Anubha Mahajan, Riccardo E. Marioni, Evelin Mihailov, Joel Eriksson, Ayse Bilge Ozel, Weihua Zhang, Maria Nethander, Yu-Ching Cheng, Stella Aslibekyan, Wei Ang, Ilaria Gandin, Loïc Yengo, Laura Portas, Charles Kooperberg, Edith Hofer, Kumar B. Rajan, Claudia Schurmann, Wouter den Hollander, Tarunveer S. Ahluwalia, Jing Zhao, Harmen H.M. Draisma, Ian Ford, Nicholas Timpson, Alexander Teumer, Hongyan Huang, Simone Wahl, YongMei Liu, Jie Huang, Hae-Won Uh, Frank Geller, Peter K. Joshi, Lisa R. Yanek, Elisabetta Trabetti, Benjamin Lehne, Diego Vozzi, Marie Verbanck, Ginevra Biino, Yasaman Saba, Ingrid Meulenbelt, Jeff R. O’Connell, Markku Laakso, Franco Giulianini, Patrik K.E. Magnusson, Christie M. Ballantyne, Jouke Jan Hottenga, Grant W. Montgomery, Fernando Rivadineira, Rico Rueedi, Maristella Steri, Karl-Heinz Herzig, David J. Stott, Cristina Menni, Mattias Frånberg, Beate St. Pourcain, Stephan B. Felix, Tune H. Pers, Stephan J.L. Bakker, Peter Kraft, Annette Peters, Dhananjay Vaidya, Graciela Delgado, Johannes H. Smit, Vera Großmann, Juha Sinisalo, Ilkka Seppälä, Stephen R. Williams, Elizabeth G. Holliday, Matthijs Moed, Claudia Langenberg, Katri Räikkönen, Jingzhong Ding, Harry Campbell, Michele M. Sale, Yii-Der I. Chen, Alan L. James, Daniela Ruggiero, Nicole Soranzo, Catharina A. Hartman, Erin N. Smith, Gerald S. Berenson, Christian Fuchsberger, Dena Hernandez, Carla M.T. Tiesler, Vilmantas Giedraitis, David Liewald, Krista Fischer, Dan Mellström, Anders Larsson, Yunmei Wang, William R. Scott, Matthias Lorentzon, John Beilby, Kathleen A. Ryan, Craig E. Pennell, Dragana Vuckovic, Beverly Balkau, Maria Pina Concas, Reinhold Schmidt, Carlos F. Mendes de Leon, Erwin P. Bottinger, Margreet Kloppenburg, Lavinia Paternoster, Michael Boehnke, A.W. Musk, Gonneke Willemsen, David M. Evans, Pamela A.F. Madden, Mika Kähönen, Zoltán Kutalik, Magdalena Zoledziewska, Ville Karhunen, Stephen B. Kritchevsky, Naveed Sattar, Genevieve Lachance, Robert Clarke, Tamara B. Harris, Olli T. Raitakari, John R. Attia, Diana van Heemst, Eero Kajantie, Rossella Sorice, Giovanni Gambaro, Robert A. Scott, Andrew A. Hicks, Luigi Ferrucci, Marie Standl, Cecilia M. Lindgren, John M. Starr, Magnus Karlsson, Lars Lind, Jun Z. Li, John C. Chambers, Trevor A. Mori, Eco J.C.N. de Geus, Andrew C. Heath, Nicholas G. Martin, Juha Auvinen, Brendan M. Buckley, Anton J.M. de Craen, Melanie Waldenberger, Konstantin Strauch, Thomas Meitinger, Rodney J. Scott, Mark McEvoy, Marian Beekman, Cristina Bombieri, Paul M. Ridker, Karen L. Mohlke, Nancy L. Pedersen, Alanna C. Morrison, Dorret I. Boomsma, John B. Whitfield, David P. Strachan, Albert Hofman, Peter Vollenweider, Francesco Cucca, Marjo-Riitta Jarvelin, J. Wouter Jukema, Tim D. Spector, Anders Hamsten, Tanja Zeller, André G. Uitterlinden, Matthias Nauck, Vilmundur Gudnason, Lu Qi, Harald Grallert, Ingrid B. Borecki, Jerome I. Rotter, Winfried März, Philipp S. Wild, Marja-Liisa Lokki, Michael Boyle, Veikko Salomaa, Mads Melbye, Johan G. Eriksson, James F. Wilson, Brenda W.J.H. Penninx, Diane M. Becker, Bradford B. Worrall, Greg Gibson, Ronald M. Krauss, Marina Ciullo, Gianluigi Zaza, Nicholas J. Wareham, Albertine J. Oldehinkel, Lyle J. Palmer, Sarah S. Murray, Peter P. Pramstaller, Stefania Bandinelli, Joachim Heinrich, Erik Ingelsson, Ian J. Deary, Reedik Mägi, Liesbeth Vandenput, Pim van der Harst, Karl C. Desch, Jaspal S. Kooner, Claes Ohlsson, Caroline Hayward, Terho Lehtimäki, Alan R. Shuldiner, Donna K. Arnett, Lawrence J. Beilin, Antonietta Robino, Philippe Froguel, Mario Pirastu, Tine Jess, Wolfgang Koenig, Ruth J.F. Loos, Denis A. Evans, Helena Schmidt, George Davey Smith, P. Eline Slagboom, Gudny Eiriksdottir, Andrew P. Morris, Bruce M. Psaty, Russell P. Tracy, Ilja M. Nolte, Eric Boerwinkle, Sophie Visvikis-Siest, Alex P. Reiner, Myron Gross, Joshua C. Bis, Lude Franke, Oscar H. Franco, Emelia J. Benjamin, Daniel I. Chasman, Josée Dupuis, Harold Snieder, Abbas Dehghan, Behrooz Z. Alizadeh, H. Marike Boezen, Gerjan Navis, Marianne Rots, Morris Swertz, Bruce H.R. Wolffenbuttel, Cisca Wijmenga, Emelia Benjamin, Tarunveer Singh Ahluwalia, James Meigs, Russell Tracy, Josh Bis, Nathan Pankratz, Alex Rainer, James G. Wilson, Josee Dupuis, Bram Prins, Urmo Vaso, Maria Stathopoulou, Terho Lehtimaki, Yalda Jamshidi, Sophie Siest, Andre G. Uitterlinden, Mohammadreza Abdollahi, Renate Schnabel, Ursula M. Schick, Aldi Kraja, Yi-Hsiang Hsu, Daniel S. Tylee, Alyson Zwicker, Rudolf Uher, George Davey-Smith, Andrew Hicks, Cornelia M. van Duijn, Cavin Ward-Caviness, J. Rotter, Ken Rice, Leslie Lange, Eco de Geus, Kari Matti Makela, David Stacey, Johan Eriksson, Tim M. Frayling, Eline P. Slagboom, Erasmus University Medical Center [Rotterdam] (Erasmus MC), University Medical Center Groningen [Groningen] (UMCG), University of Isfahan, University of Tartu, Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), The University of Texas Health Science Center at Houston (UTHealth), National Institute on Aging [Bethesda, USA] (NIA), National Institutes of Health [Bethesda] (NIH), Brigham and Women's Hospital [Boston], University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], University of Split, Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Process & Energy Laboratory, Delft University of Technology (TU Delft), Grand Lyon : communauté urbaine de Lyon, Interuniversity Cardiology Institute Netherlands, Department of Twin Research and Genetic Epidemiology, King's College London, London, Huazhong University of Science and Technology [Wuhan] (HUST), Division of Statistical Genomics, Washington University School of Medicine, Department of Psychiatry, VU University Medical Center [Amsterdam], Institut fuer Theoretische Physik (Institut fuer Theoretische Physik), Universität Heidelberg [Heidelberg] = Heidelberg University, Molecular Epidemiology, MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Mahidol University [Bangkok], Northwest A and F University, Laboratoire d'Optimisation des Systèmes Industriels (LOSI), Institut Charles Delaunay (ICD), Université de Technologie de Troyes (UTT)-Centre National de la Recherche Scientifique (CNRS)-Université de Technologie de Troyes (UTT)-Centre National de la Recherche Scientifique (CNRS), Institute of Genetics and Biophysics, CNR, Naples, Università degli studi di Verona = University of Verona (UNIVR), Department of Molecular Medicine [Scripps Research Institute], The Scripps Research Institute [La Jolla, San Diego], Department of Physics, Indian Institute of Technology Kanpur (IIT Kanpur), Deptartment of Medical Biochemistry and Microbiology, Uppsala University, Department of Electrical and Computer Engineering [Waterloo] (ECE), University of Waterloo [Waterloo], University of Maryland School of Medicine, University of Maryland System, Institut National de l'Environnement Industriel et des Risques (INERIS), Institute of Pop. Genetics, CNR, Sassari, Interfaculty Institute for Genetics and Functional Genomics, Universität Greifswald - University of Greifswald, IT University of Copenhagen (ITU), Robertson Centre for Biostatistics, University of Glasgow, Centre for Causal Analyses in Translational Epidemiology, University of Bristol [Bristol]-Medical Research Council, King‘s College London, Jinan University [Guangzhou], Institute of Oceanology [China], School Medicine, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), General Internal Medicine, Johns Hopkins School of Medicine, Johns Hopkins University School of Medicine [Baltimore], Shardna life science Pula Cagliari, Section Molecular Epidemiology, Leiden University Medical Center (LUMC), Department of Medicine, University of Eastern Finland-Kuopio University Hospital, Medstar Research Institute, Department of Cardiology, Ernst-Moritz-Arndt University, Center for Biological Sequence Analysis [Lyngby], Danmarks Tekniske Universitet = Technical University of Denmark (DTU), Department of Internal Medicine, University of Groningen and University Medical Center Groningen, Department of Epidemiology, Harvard School of Public Health, German Research Center for Environmental Health - Helmholtz Center München (GmbH), Metacohorts Consortium, INEOS Technologies (SWITZERLAND), MRC Epidemiology Unit, University of Cambridge [UK] (CAM)-Institute of Metabolic Science, University of Edinburgh, School of Population Health [Crawley, Western Australia], The University of Western Australia (UWA), Institute of Genetics and Biophysics, National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), The Scripps Translational Science Institute and Scripps Health, Tulane Center for Cardiovascular Health, Tulane University Health Sciences Center, Centre for Population Health Sciences, Genomic Research Laboratory, Service of Infectious Disease, Hôpitaux Universitaires de Genève (HUG), Infectious diseases division, Department of internal medicine, Washington University in Saint Louis (WUSTL), Luleå University of Technology (LUT), Recherche en épidémiologie et biostatistique, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Austrian Institute of Technology [Vienna] (AIT), Icahn School of Medicine at Mount Sinai [New York] (MSSM), Department of Rheumatology and Clinical Epidemiology, Leiden University Medical Center (LUMC), Department of Rheumatology and Clinical Epidemiology [Leiden University Medical Center] (LUMC), Leiden University Medical Center (LUMC), Universiteit Leiden-Universiteit Leiden-Leiden University Medical Center (LUMC), Universiteit Leiden-Universiteit Leiden, Department of Biostatistics and Center for Statistical Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, University of Virginia, Tampere University Hospital, Department of Medical Genetics, Université de Lausanne = University of Lausanne (UNIL), Department of Pathological Biochemistry, Royal Infirmary, Oxford University, University of Oxford, University of Newcastle [Callaghan, Australia] (UoN), Department of neurology, Institute of Metabolic Science, MRC, The Wellcome Trust Centre for Human Genetics [Oxford], Uppsala Universitet [Uppsala], QIMR Berghofer Medical Research Institute, Institute of Genetic Epidemiology [Neuherberg, Germany], Institute of Human Genetics, Helmholtz Zentrum München = German Research Center for Environmental Health, Schizophrenia Research Institute [Sydney], Department of Genetics, University of North Carolina System (UNC)-University of North Carolina System (UNC), Vrije Universiteit Brussel (VUB), Population Health Sciences and Education, St George's University of London, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Institute of Health Sciences and Biocenter Oulu, University of Oulu, Medizinische Klinik und Poliklinik, Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Institute of Clinical Chemistry and Laboratory Medicine, Icelandic Heart Association, Heart Preventive Clinic and Research Institute, Departments of Epidemiology and Nutrition, Institute of Epidemiology [Neuherberg] (EPI), Medical University Graz, Transplantation Laboratory [Helsinki], Haartman Institute [Helsinki], Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Department of Chronic Disease Prevention, National Institute for Health and Welfare [Helsinki], Dept. of Epidemiology Research, Statens Serum Institut [Copenhagen], CLinical Psychology, Genetics and Pathology, Geriatric Rehabilitation Unit, Azienda Sanitaria Firenze, Center For Narcolepsy, Stanford University, Centre for Bone and Arthritis Research, University of Gothenburg (GU)-Institute of Medicine, MRC Human Gentics Unit, Inst Genet and Mol Med, Western General Hospital, Edinburgh, University of Maryland School of Medicine [Baltimore, MD, USA], Génétique des maladies multifactorielles (GMM), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Department of Physics [Stockholm], Stockholm University, University of Bristol [Bristol], Universiteit Leiden, Department of Epidemiology, University of Washington, University of Washington [Seattle], Department of Epidemiology [Rotterdam], University of Groningen [Groningen], Dutch Initiative on Crohn and Colitis (ICC), Icelandic Heart Association [Kopavogur, Iceland] (IHA), Department of Physiology and Biophysics [Jackson, MS, USA], University of Southern Mississippi (USM), Human Genetics Branch, National Institutes of Health [Bethesda] (NIH)-National Institute of Mental Health (NIMH), Faculty of Medicine and Life Sciences [Tampere], University of Tampere [Finland], German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), MRC Centre for Neuropsychiatric Genetics and Genomics, Medical Research Council-Cardiff University, Department of Social Medicine, School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), Department of Medicine [Aurora, CO, USA], University of Colorado [Denver], Institute for Molecular Medicine Finland [Helsinki] (FIMM), Helsinki Institute of Life Science (HiLIFE), Mathematical Institute [Oxford] (MI), Institute of Psychiatry, Psychology & Neuroscience, King's College London, LifeLines Cohort Study, CHARGE Inflammation Working Group, Ligthart, S., Vaez, A., Vosa, U., Stathopoulou, M. G., de Vries, P. S., Prins, B. P., Van der Most, P. J., Tanaka, T., Naderi, E., Rose, L. M., Wu, Y., Karlsson, R., Barbalic, M., Lin, H., Pool, R., Zhu, G., Mace, A., Sidore, C., Trompet, S., Mangino, M., Sabater-Lleal, M., Kemp, J. P., Abbasi, A., Kacprowski, T., Verweij, N., Smith, A. V., Huang, T., Marzi, C., Feitosa, M. F., Lohman, K. K., Kleber, M. E., Milaneschi, Y., Mueller, C., Huq, M., Vlachopoulou, E., Lyytikainen, L. -P., Oldmeadow, C., Deelen, J., Perola, M., Zhao, J. H., Feenstra, B., Alizadeh, B. Z., Boezen, H. M., Franke, L., van der Harst, P., Navis, G., Rots, M., Snieder, H., Swertz, M., Wolffenbuttel, B. H. R., Wijmenga, C., Amini, M., Benjamin, E., Chasman, D. I., Dehghan, A., Ahluwalia, T. S., Meigs, J., Tracy, R., Bis, J., Eiriksdottir, G., Pankratz, N., Gross, M., Rainer, A., Wilson, J. G., Psaty, B. M., Dupuis, J., Prins, B., Vaso, U., Stathopoulou, M., Lehtimaki, T., Koenig, W., Jamshidi, Y., Siest, S., Uitterlinden, A. G., Abdollahi, M., Schnabel, R., Schick, U. M., Nolte, I. M., Kraja, A., Hsu, Y. -H., Tylee, D. S., Zwicker, A., Uher, R., Davey-Smith, G., Morrison, A. C., Hicks, A., van Duijn, C. M., Ward-Caviness, C., Boerwinkle, E., Rotter, J., Rice, K., Lange, L., de Geus, E., Morris, A. P., Makela, K. M., Stacey, D., Eriksson, J., Frayling, T. M., Slagboom, E. P., Lahti, J., Schraut, K. E., Fornage, M., Suktitipat, B., Chen, W. -M., Li, X., Nutile, T., Malerba, G., Luan, J., Bak, T., Schork, N., Del Greco, M. F., Thiering, E., Mahajan, A., Marioni, R. E., Mihailov, E., Ozel, A. B., Zhang, W., Nethander, M., Cheng, Y. -C., Aslibekyan, S., Ang, W., Gandin, I., Yengo, L., Portas, L., Kooperberg, C., Hofer, E., Rajan, K. B., Schurmann, C., den Hollander, W., Zhao, J., Draisma, H. H. M., Ford, I., Timpson, N., Teumer, A., Huang, H., Wahl, S., Liu, Y., Huang, J., Uh, H. -W., Geller, F., Joshi, P. K., Yanek, L. R., Trabetti, E., Lehne, B., Vozzi, D., Verbanck, M., Biino, G., Saba, Y., Meulenbelt, I., O'Connell, J. R., Laakso, M., Giulianini, F., Magnusson, P. K. E., Ballantyne, C. M., Hottenga, J. J., Montgomery, G. W., Rivadineira, F., Rueedi, R., Steri, M., Herzig, K. -H., Stott, D. J., Menni, C., Franberg, M., S, t. Pourcain B., Felix, S. B., Pers, T. H., Bakker, S. J. L., Kraft, P., Peters, A., Vaidya, D., Delgado, G., Smit, J. H., Grossmann, V., Sinisalo, J., Seppala, I., Williams, S. R., Holliday, E. G., Moed, M., Langenberg, C., Raikkonen, K., Ding, J., Campbell, H., Sale, M. M., Chen, Y. -D. I., James, A. L., Ruggiero, D., Soranzo, N., Hartman, C. A., Smith, E. N., Berenson, G. S., Fuchsberger, C., Hernandez, D., Tiesler, C. M. T., Giedraitis, V., Liewald, D., Fischer, K., Mellstrom, D., Larsson, A., Wang, Y., Scott, W. R., Lorentzon, M., Beilby, J., Ryan, K. A., Pennell, C. E., Vuckovic, D., Balkau, B., Concas, M. P., Schmidt, R., Mendes de Leon, C. F., Bottinger, E. P., Kloppenburg, M., Paternoster, L., Boehnke, M., Musk, A. W., Willemsen, G., Evans, D. M., Madden, P. A. F., Kahonen, M., Kutalik, Z., Zoledziewska, M., Karhunen, V., Kritchevsky, S. B., Sattar, N., Lachance, G., Clarke, R., Harris, T. B., Raitakari, O. T., Attia, J. R., van Heemst, D., Kajantie, E., Sorice, R., Gambaro, G., Scott, R. A., Hicks, A. A., Ferrucci, L., Standl, M., Lindgren, C. M., Starr, J. M., Karlsson, M., Lind, L., Li, J. Z., Chambers, J. C., Mori, T. A., de Geus, E. J. C. N., Heath, A. C., Martin, N. G., Auvinen, J., Buckley, B. M., de Craen, A. J. M., Waldenberger, M., Strauch, K., Meitinger, T., Scott, R. J., Mcevoy, M., Beekman, M., Bombieri, C., Ridker, P. M., Mohlke, K. L., Pedersen, N. L., Boomsma, D. I., Whitfield, J. B., Strachan, D. P., Hofman, A., Vollenweider, P., Cucca, F., Jarvelin, M. -R., Jukema, J. W., Spector, T. D., Hamsten, A., Zeller, T., Nauck, M., Gudnason, V., Qi, L., Grallert, H., Borecki, I. B., Rotter, J. I., Marz, W., Wild, P. S., Lokki, M. -L., Boyle, M., Salomaa, V., Melbye, M., Eriksson, J. G., Wilson, J. F., Penninx, B. W. J. H., Becker, D. M., Worrall, B. B., Gibson, G., Krauss, R. M., Ciullo, M., Zaza, G., Wareham, N. J., Oldehinkel, A. J., Palmer, L. J., Murray, S. S., Pramstaller, P. P., Bandinelli, S., Heinrich, J., Ingelsson, E., Deary, I. J., Magi, R., Vandenput, L., Desch, K. C., Kooner, J. S., Ohlsson, C., Hayward, C., Shuldiner, A. R., Arnett, D. K., Beilin, L. J., Robino, A., Froguel, P., Pirastu, M., Jess, T., Loos, R. J. F., Evans, D. A., Schmidt, H., Slagboom, P. E., Tracy, R. P., Visvikis-Siest, S., Reiner, A. P., Bis, J. C., Franco, O. H., Benjamin, E. J., AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Graduate School, Epidemiology, Internal Medicine, Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Cardiovascular Centre (CVC), Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Stem Cell Aging Leukemia and Lymphoma (SALL), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), VU University medical center, Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, APH - Methodology, APH - Digital Health, Biological Psychology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Universität Heidelberg [Heidelberg], University of Verona (UNIVR), Department of Molecular and Experimental Medicine, The Scripps Research Institute, The Scripps Research Institute, Université Grenoble Alpes - UFR Sciences de l'Homme et de la Société (UGA UFR SHS), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), IT University of Copenhagen, Technical University of Denmark [Lyngby] (DTU), Consiglio Nazionale delle Ricerche (CNR), University of Virginia [Charlottesville], Université de Lausanne (UNIL), University of Oxford [Oxford], University of Newcastle [Australia] (UoN), Centre d'économie industrielle i3 (CERNA i3), Centre National de la Recherche Scientifique (CNRS)-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Helmholtz-Zentrum München (HZM), Laboratoire Interuniversitaire des Systèmes Atmosphériques (LISA (UMR_7583)), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Universitätsmedizin der Johannes-Gutenberg Universität Mainz, University of Helsinki-University of Helsinki-Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, Cardiff University-Medical Research Council, University of California-University of California, and DE CARVALHO, Philippe
Subjects: 0301 basic medicine, Male, Netherlands Twin Register (NTR), Bipolar Disorder, LD SCORE REGRESSION, [SDV]Life Sciences [q-bio], Genome-wide association study, [SDV.GEN] Life Sciences [q-bio]/Genetics, Body Mass Index, inflammatory disorder, 80 and over, WIDE ASSOCIATION, EPIDEMIOLOGY, ta318, International HapMap Project, Child, Genetics (clinical), 2. Zero hunger, Genetics, Genetics & Heredity, Aged, 80 and over, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, C-reactive proteingenome-wide association studyinflammationMendelian randomizationinflammatory disordersDEPICTcoronary artery diseaseschizophreniasystem biology, system biology, DEPICT, Mendelian Randomization Analysis, 11 Medical And Health Sciences, Middle Aged, C-reactive protein, coronary artery disease, genome-wide association study, inflammation, inflammatory disorders, Mendelian randomization, schizophrenia, Adolescent, Adult, Aged, Biomarkers, C-Reactive Protein, Female, Genetic Loci, Genome-Wide Association Study, Humans, Inflammation, Liver, Metabolic Networks and Pathways, Schizophrenia, Young Adult, 3. Good health, [SDV] Life Sciences [q-bio], Medical genetics, Biomarker (medicine), Life Sciences & Biomedicine, Human, medicine.medical_specialty, CHARGE Inflammation Working Group, Biology, IMMUNITY, ta3111, Article, 03 medical and health sciences, SDG 3 - Good Health and Well-being, medicine, CORONARY-HEART-DISEASE, Mendelian Randomization Analysi, 1000 Genomes Project, METAANALYSIS, Genetic association, [SDV.GEN]Life Sciences [q-bio]/Genetics, Science & Technology, ta1184, Metabolic Networks and Pathway, Biomarker, INSTRUMENTS, 06 Biological Sciences, 030104 developmental biology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, LifeLines Cohort Study
Abstract: International audience; C-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204,402 European individuals. Additionally, we performed in silico functional analyses and Mendelian randomization analyses with several clinical outcomes. The GWAS meta-analyses of CRP revealed 58 distinct genetic loci (p < 5 × 10-8). After adjustment for body mass index in the regression analysis, the associations at all except three loci remained. The lead variants at the distinct loci explained up to 7.0% of the variance in circulating amounts of CRP. We identified 66 gene sets that were organized in two substantially correlated clusters, one mainly composed of immune pathways and the other characterized by metabolic pathways in the liver. Mendelian randomization analyses revealed a causal protective effect of CRP on schizophrenia and a risk-increasing effect on bipolar disorder. Our findings provide further insights into the biology of inflammation and could lead to interventions for treating inflammation and its clinical consequences.Copyright © 2018 American Society of Human Genetics. All rights reserved.
Published: 2018

30. Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990-2013

Author: Meghan D. Mooney, Ken Takahashi, Andrea Stewart, Jonathan C Brown, Shireen Sindi, Amany H Refaat, Ruben Castro, Sara Sheikhbahaei, Kyle R. Heuton, Gillian M. Hansen, Chante Karimkhani, Bryan K. Phillips, Ibrahim Abubakar, Yohannes Kinfu, Victoria F Bachman, Konstantinos Stroumpoulis, Megan Coggeshall, Lucía Cuevas-Nasu, Yichong Li, Vineet K. Chadha, Andrew G. M. Bulloch, Takayoshi Ohkubo, Don C. Des Jarlais, Giancarlo Logroscino, Francis Apolinary Mhimbira, Jefferson G Fernandes, Cheng Huang, Ejaz Ahmad Khan, Fortuné Gbètoho Gankpé, Roderick J Hay, Itamar S. Santos, Zanfina Ademi, Fiona J Charlson, Norlinah Mohamed Ibrahim, Anwar Rafay, Andrew L. Thorne-Lyman, Juanita A. Haagsma, Emmanuel A. Ameh, John J. McGrath, Massimo Cirillo, Wubegzier Mekonnen, Holly Hagan, Naohiro Yonemoto, Frida Namnyak Ngalesoni, Dietrich Plass, Matias Trillini, David Phillips, Braden Te Ao, Wanqing Chen, Yun Jin Kim, David Rojas-Rueda, Christina Papachristou, Andrew E. Moran, Richard A. Gosselin, Maziar Moradi-Lakeh, Soraya Seedat, Janet L Leasher, Belinda K Lloyd, Lorenzo Monasta, Bruno F. Sunguya, Eun-Kee Park, Eduardo A. Undurraga, Mohammad A. AlMazroa, Mohammad H. Forouzanfar, Young-Ho Khang, Vasiliki Stathopoulou, Dima M. Qato, James Scott, Ileana Heredia-Pi, Luca Ronfani, Haidong Kan, Tasara T. Mazorodze, Murugesan Raju, Saeid Shahraz, Taavi Tillmann, Wang Wenzhi, Neil Pearce, Eric Y. Tenkorang, Aliya Naheed, Ferrán Catalá-López, Sudan Prasad Neupane, Emily Dansereau, Michael McKee, Derrick A Bennett, Mazeda Hossain, Paul S. F. Yip, Grant Nguyen, Norberto Perico, Miguel Angel Alegretti, Babak Eshrati, Boris Bikbov, Palwasha Anwari, Guoqing Hu, Amelia Bertozzi-Villa, Peter A. Meaney, Farshad Farzadfar, Svetlana Popova, Tara Templin, Hmwe H Kyu, Uche S. Uchendu, Kebede Deribe, Sergey Soshnikov, Nobhojit Roy, Daniel Kim, Ilana N. Ackerman, Homie Razavi, Leslie T. Cooper, Sandra Nolte, David T. Felson, John J Huang, Yang Liu, Fiorella Cavalleri, Adrian Davis, Héctor Gómez Dantés, Klara Dokova, Yuantao Hao, Catalina Medina, Austin E Schumacher, Stan Biryukov, Jane Rowley, Arindam Basu, Jose C. Adsuar, Rosana E. Norman, Yousef Khader, Rafael Alfonso-Cristancho, Sukanta Saha, Simón Barquera, Diego Gonzalez-Medina, Philip B. Mitchell, Lars Barregard, Haidong Wang, Yongmei Li, Ami R. Moore, Marie Ng, Raghib Ali, Peter T. Serina, Lijing L Yan, Ayse Abbasoglu Ozgoren, Ricky Leung, Michelle L. Bell, Tim Driscoll, Azmeraw T. Amare, Farshad Pourmalek, Tea Lallukka, Benjamin O Anderson, Raimundas Lunevicius, Corine Karema, Robert G. Weintraub, Erin C Mullany, Anders Larsson, Glen Mola, Paulo A. Lotufo, Luke Nyakarahuka, Sayed Saidul Alam, Louisa Degenhardt, Hugh R. Taylor, E. Ray Dorsey, Suzanne Polinder, Hilton Lam, Urbano Fra Paleo, David Zonies, Rahman Shiri, Marco A Avila, Alicia Elena Beatriz Lawrynowicz, Katya Anne Shackelford, Lynne Gaffikin, Konstantin Kazanjan, Mark T Mackay, Jasvinder A. Singh, Bryan L. Sykes, Sadaf G. Sepanlou, Chantal Huynh, Rakhi Dandona, Logan Sandar, Lavanya Singh, Dietrich Rothenbacher, Theo Vos, Steven E. Lipshultz, Coen H. Van Gool, Peggy P. Chiang, Mark G. Shrime, Christopher J L Murray, Scott Weichenthal, Jae-Hyun Park, Samia Alhabib, Philimon Gona, Christian Kieling, Yuichiro Yano, Ronny Westerman, Thomas Truelsen, Rajeev Gupta, Megan Bohensky, Abdullatif Husseini, Qing Lan, Luke D. Knibbs, Yousef M. Elshrek, H. Ross Anderson, Guohong Jiang, Madeline L. Moyer, Vinod K. Paul, Wim H. van Brakel, Emin Murat Tuzcu, Kara Estep, Lalit Dandona, Uchechukwu K.A. Sampson, Mohammad Tavakkoli, Ying Jiang, Joseph A Wagner, Mitsuru Mukaigawara, In-Hwan Oh, Siyi Shangguan, Noela M. Prasad, Charles D.A. Wolfe, Borja del Pozo-Cruz, Gokalp Kadri Yentur, Hilda L Harb, Elena Alvarez, Carlos A Castañeda-Orjuela, Mustafa Z. Younis, Herbert C. Duber, Erica Leigh Slepak, George A. Mensah, Knud Juel, Graeme J. Hankey, Natan M. Bornstein, Martha Híjar, Johan Ärnlöv, Mohamed Hsairi, Katherine T. Lofgren, Murray B. Stein, Renata Micha, Luigi Naldi, Margreet ten Have, Bolajoko O. Olusanya, Kyle J Foreman, Kenji Shibuya, F. Gerry R. Fowkes, Abdullah Sulieman Terkawi, Rana J. Asghar, Karen M. Tabb, Kovin Naidoo, Rogelio Pérez-Padilla, Honglei Chen, Antônio Luiz Pinho Ribeiro, Rasmus Havmoeller, Yukito Shinohara, Bongani M. Mayosi, Ernst J Kuipers, Konrad Pesudovs, Mouhanad Hammami, Lee Richardson, Rintaro Mori, Thomas D. Fleming, Pouria Heydarpour, Stephen G. Waller, Nicholas Graetz, Chanda Kulkarni, Peter Brooks, Gulfaraz Khan, Marcel Tanner, Van C. Lansingh, François Alla, Jamie Hancock, Yohannes Adama Melaku, Neeraj Bedi, Anthony D. Woolf, Tariku Jibat Beyene, Amanda W Pain, Eric L. Ding, Narayanaswamy Venketasubramanian, Semaw Ferede Abera, Devina Nand, Odgerel Chimed-Ochir, George D Thurston, Victor Aboyans, Alanur Çavlin, Jefferson Traebert, Michael R. Phillips, Yingfeng Zheng, Baffour Awuah, Carlo Irwin A. Panelo, Selen Begüm Uzun, Muhammad Imran Nisar, Samir Soneji, Veena S. Kulkarni, Mukesh Dherani, Stephen S Lim, Andre Keren, Kingsley N. Ukwaja, Sajjad Ur Rahman, Giuseppe Remuzzi, Kjetil Søreide, Blake Thomson, Samath D Dharmaratne, Christopher D. Blosser, David H. Rothstein, Amanda G. Thrift, Fabrizio Tediosi, Andrew H. Kemp, H. Dean Hosgood, Yoshihiro Kokubo, Miia Kivipelto, Amitava Banerjee, Edgar P. Simard, Reza Malekzadeh, Maggie Lind, Robert P. Dellavalle, Emerito Jose A. Faraon, Lydia S. Atkins, Tom Achoki, Aslam Pervaiz, Peter Scarborough, Hans W. Hoek, Ettore Beghi, Emilie Agardh, Abraham D. Flaxman, Dariush Mozaffarian, Juan R. Sanabria, Muluken Dessalegn, David C. Schwebel, Caitlyn Steiner, Ubai Alsharif, Richard C. Franklin, Gail Davey, Gelin Xu, Reyna A Gutiérrez, Joannie Lortet-Tieulent, Ashish Bhalla, Jost B. Jonas, Paul N. Jensen, Simon I. Hay, Xiaonong Zou, Andre Pascal Kengne, Tolesa Bekele, Brittany Wurtz, Jung-Chen Chang, Joseph Murray, Luciano A. Sposato, Stefan Ma, Summer Lockett Ohno, Charles R. Newton, Bradford D. Gessner, JianLi Wang, Scott B. Patten, Thomas Fürst, Carol Brayne, Christina Fitzmaurice, Peilin Shi, Ted R. Miller, Kinnari S. Murthy, Habib Benzian, Peter W. Gething, Cesar Diaz-Torne, Burcu Kucuk Bicer, Bo Norrving, Carly E Levitz, Adam D M Briggs, Sungroul Kim, Isabela M. Benseñor, John A. Crump, Sergey Petrovich Ermakov, Kalpana Balakrishnan, Awoke Misganaw Temesgen, Marcella Montico, Sanjay Krishnaswami, Kim Moesgaard Iburg, Ann Kristin Knudsen, Sun Ha Jee, Valery L. Feigin, Christine M. Budke, Anne Bulchis, Anand Dayama, Jonathan R. Carapetis, Cyrus Cooper, Teresa Shamah Levy, Ismael R. Campos-Nonato, Nataliya A. Foigt, Beth E. Ebel, Max Petzold, Heresh Amini, Ole Frithjof Norheim, Zulfiqar A Bhutta, Dan Poenaru, Jim van Os, Michele E. Murdoch, Samantha M. Colquhoun, Michael H. Criqui, Giorgia Giussani, Man Mohan Mehndiratta, Thomas N. Williams, Chandrashekhar T Sreeramareddy, Chuanhua Yu, Luis M. Coppola, Thomas J. Montine, Alaa Badawi, Eduardo Bernabé, Melvin Barrientos Marzan, James Leigh, Frédéric B. Piel, Ratilal Lalloo, Panniyammakal Jeemon, Maheswar Satpathy, Hélène Carabin, Corina Benjet, Seyed-Mohammad Fereshtehnejad, Ryan M Barber, Fotis Topouzis, Bin Li, Serge Resnikoff, Taavi Lai, Rachelle Buchbinder, Randah R. Hamadeh, Valeria Caso, Holly E. Erskine, Dragos Virgil Davitoiu, Miltiadis K. Tsilimbaris, Rachel L. Pullan, Ben Schöttker, Rafael Lozano, Damian G Hoy, Fiona M. Blyth, Belinda J. Gabbe, Hebe N. Gouda, Farhad Islami, Atte Meretoja, Christopher Margono, Marissa Iannarone, Ronan A Lyons, Wilkister N. Moturi, Donald H. Silberberg, Alexandra Brazinova, Monica Cortinovis, Deena Alasfoor, Richard Matzopoulos, Jerry Abraham, Francesco Saverio Violante, Monika Sawhney, Dorairaj Prabhakaran, Valentina Colistro, Derek F J Fay, Mamta Swaroop, Nima Hafezi-Nejad, John Nelson Opio, Hanne Christensen, Jun She, Soewarta Kosen, Atsushi Goto, Costas A. Christophi, Jeyaraj D. Pandian, Peter J. Hotez, K. Srinath Reddy, Al Artaman, Peter Allebeck, Jonas Minet Kinge, Graham S Cooke, Dan J. Stein, Kawkab Shishani, Laith J. Abu-Raddad, Katrina F Ortblad, Deborah Jarvis, Arsène Kouablan Adou, Barthelemy Kuate Defo, Alan D. Lopez, G Anil Kumar, K.M. Venkat Narayan, Yong Zhao, Rajiv Chowdhury, Hadi Danawi, George C Patton, Vasiliy Victorovich Vlassov, André Karch, Tommi J. Vasankari, Matthias Endres, Ione Jayce Ceola Schneider, Nelson Alvis-Guzman, Charles N Mock, Katharine J Looker, Bach Xuan Tran, Fernando Perez-Ruiz, Harish Chander Gugnani, Reza Assadi, Hannah Hamavid, Rosario Cárdenas, Mohammed I. Albittar, Sarah Derrett, Mohammad Yahya Saeedi, Traolach S. Brugha, Jan Hendrik Richardus, Alireza Esteghamati, Seok Jun Yoon, Josep Maria Haro, Michael Brainin, Ziad A. Memish, Rupert R A Bourne, Katherine B Gibney, David M. Pereira, Kathryn H. Jacobsen, Luc E. Coffeng, Joshua A. Salomon, Xia Wan, Ian Bolliger, Boris I. Pavlin, Karen Sliwa, Tati S. Warouw, Geoffrey Buckle, Chakib Nejjari, Diego De Leo, Ashkan Afshin, Vinay Nangia, Daniel Pope, Johanna M. Geleijnse, Nikhil Tandon, Kelly Bienhoff, Jed D. Blore, Walid Ammar, D. Allen Roberts, Elisabete Weiderpass, Gregory A. Roth, Manami Inoue, James D. Wilkinson, Hideaki Toyoshima, Soufiane Boufous, Ivy Shiue, Edward J Mills, Leilei Duan, Matthew M Coates, Ganesan Karthikeyan, Alberto Ortiz, Steven van de Vijver, David Carpenter, Suzanne Lyn Barker-Collo, Antony Stevens, Sanjay Basu, Maria Cecilia Bahit, Kaire Innos, Lindsay N. Boyers, Nicholas J K Breitborde, Alize J. Ferrari, Timothy M. Wolock, Simerjot K. Jassal, Mohammad Ali Sahraian, Joanna Moschandreas, Howard J. Hoffman, Hideki Higashi, George M. Ruhago, Karzan Abdulmuhsin Mohammad, Mohammed Basulaiman, D. Alex Quistberg, Justin Beardsley, Marcello Tonelli, Maurice Giroud, Karen Edmond, Norito Kawakami, Mohammad T Mashal, Neeraj Bhala, Carl Abelardo T. Antonio, David Tanne, Abhishek Singh, Kazem Rahimi, Vivekanand Jha, Wagner Marcenes, David J. Margolis, Yara A. Halasa, Zewdie Aderaw Alemu, Carrie Beth Peterson, Edson Serván-Mori, Anil Kaul, Foad Abd-Allah, Marek Majdan, Rahul Gupta, Robyn M. Lucas, Sarah Wulf, Lars Jacob Stovner, Mohsen Naghavi, Vegard Skirbekk, Ulrich Otto Mueller, Pengpeng Ye, Ali H. Mokdad, Dipan Bose, Saleem M Rana, Jeffrey D Stanaway, Abigail Mclain, Timothy J. Steiner, Amira Shaheen, Stein Emil Vollset, Andrea Werdecker, Michele Meltzer, Richie G Poulton, Joseph R. Masci, Inga Dora Sigfusdottir, Daniel Dicker, Maysaa El Sayed Zaki, Shiwei Liu, Julio C. Montañez Hernandez, Valentina Arsić Arsenijević, William Msemburi, Lope H Barrero, Linhong Wang, Soumya Swaminathan, Harvey Whiteford, Michael F. Macintyre, Berrak Bora Basara, Gregory R. Wagner, Paul I. Dargan, Hermann Brenner, Carolyn C. Gotay, Niveen M E Abu-Rmeileh, Nicholas J Kassebaum, Shams Eldin Ali Hassan Khalifa, Neil McGill, Murray, Christopher J. L, Barber, Ryan M., Foreman, Kyle J., Ozgoren, Ayse Abbasoglu, Abd-Allah, Foad, Abera, Semaw F., Aboyans, Victor, Abraham, Jerry P., Abubakar, Ibrahim, Abu-Raddad, Laith J., Abu-Rmeileh, Niveen M., Achoki, Tom, Ackerman, Ilana N., Ademi, Zanfina, Adou, Arsène K., Adsuar, José C., Afshin, Ashkan, Agardh, Emilie E., Alam, Sayed Saidul, Alasfoor, Deena, Albittar, Mohammed I., Alegretti, Miguel A., Alemu, Zewdie A., Alfonso-Cristancho, Rafael, Alhabib, Samia, Ali, Raghib, Alla, Françoi, Allebeck, Peter, Almazroa, Mohammad A., Alsharif, Ubai, Alvarez, Elena, Alvis-Guzman, Nelson, Amare, Azmeraw T., Ameh, Emmanuel A., Amini, Heresh, Ammar, Walid, Anderson, H. Ro, Anderson, Benjamin O., Antonio, Carl Abelardo T., Anwari, Palwasha, Arnlöv, Johan, Arsenijevic, Valentina S. Arsic, Artaman, Al, Asghar, Rana J., Assadi, Reza, Atkins, Lydia S., Avila, Marco A., Awuah, Baffour, Bachman, Victoria F., Badawi, Alaa, Bahit, Maria C., Balakrishnan, Kalpana, Banerjee, Amitava, Barker-Collo, Suzanne L., Barquera, Simon, Barregard, Lar, Barrero, Lope H., Basu, Arindam, Basu, Sanjay, Basulaiman, Mohammed O., Beardsley, Justin, Bedi, Neeraj, Beghi, Ettore, Bekele, Tolesa, Bell, Michelle L., Benjet, Corina, Bennett, Derrick A., Bensenor, Isabela M., Benzian, Habib, Bernabé, Eduardo, Bertozzi-Villa, Amelia, Beyene, Tariku J., Bhala, Neeraj, Bhalla, Ashish, Bhutta, Zulfiqar A., Bienhoff, Kelly, Bikbov, Bori, Biryukov, Stan, Blore, Jed D., Blosser, Christopher D., Blyth, Fiona M., Bohensky, Megan A., Bolliger, Ian W., Başara, Berrak Bora, Bornstein, Natan M., Bose, Dipan, Boufous, Soufiane, Bourne, Rupert R. A., Boyers, Lindsay N., Brainin, Michael, Brayne, Carol E., Brazinova, Alexandra, Breitborde, Nicholas J. K., Brenner, Hermann, Briggs, Adam D., Brooks, Peter M., Brown, Jonathan C., Brugha, Traolach S., Buchbinder, Rachelle, Buckle, Geoffrey C., Budke, Christine M., Bulchis, Anne, Bulloch, Andrew G., Campos-Nonato, Ismael R., Carabin, Hélène, Carapetis, Jonathan R., Cárdenas, Rosario, Carpenter, David O., Caso, Valeria, Castañeda-Orjuela, Carlos A., Castro, Ruben E., Catalá-López, Ferrán, Cavalleri, Fiorella, Çavlin, Alanur, Chadha, Vineet K., Chang, Jung-Chen, Charlson, Fiona J., Chen, Honglei, Chen, Wanqing, Chiang, Peggy P., Chimed-Ochir, Odgerel, Chowdhury, Rajiv, Christensen, Hanne, Christophi, Costas A., Cirillo, Massimo, Coates, Matthew M., Coffeng, Luc E., Coggeshall, Megan S., Colistro, Valentina, Colquhoun, Samantha M., Cooke, Graham S., Cooper, Cyru, Cooper, Leslie T., Coppola, Luis M., Cortinovis, Monica, Criqui, Michael H., Crump, John A., Cuevas-Nasu, Lucia, Danawi, Hadi, Dandona, Lalit, Dandona, Rakhi, Dansereau, Emily, Dargan, Paul I., Davey, Gail, Davis, Adrian, Davitoiu, Dragos V., Dayama, Anand, De Leo, Diego, Degenhardt, Louisa, Del Pozo-Cruz, Borja, Dellavalle, Robert P., Deribe, Kebede, Derrett, Sarah, Des Jarlais, Don C., Dessalegn, Muluken, Dharmaratne, Samath D., Dherani, Mukesh K., Diaz-Torné, Cesar, Dicker, Daniel, Ding, Eric L., Dokova, Klara, Dorsey, E Ray, Driscoll, Tim R., Duan, Leilei, Duber, Herbert C., Ebel, Beth E., Edmond, Karen M., Elshrek, Yousef M., Endres, Matthia, Ermakov, Sergey P., Erskine, Holly E., Eshrati, Babak, Esteghamati, Alireza, Estep, Kara, Faraon, Emerito Jose A., Farzadfar, Farshad, Fay, Derek F., Feigin, Valery L., Felson, David T., Fereshtehnejad, Seyed-Mohammad, Fernandes, Jefferson G., Ferrari, Alize J., Fitzmaurice, Christina, Flaxman, Abraham D., Fleming, Thomas D., Foigt, Nataliya, Forouzanfar, Mohammad H., Fowkes, F Gerry R., Paleo, Urbano Fra., Franklin, Richard C., Fürst, Thoma, Gabbe, Belinda, Gaffikin, Lynne, Gankpé, Fortuné G., Geleijnse, Johanna M., Gessner, Bradford D., Gething, Peter, Gibney, Katherine B., Giroud, Maurice, Giussani, Giorgia, Dantes, Hector Gomez, Gona, Philimon, González-Medina, Diego, Gosselin, Richard A., Gotay, Carolyn C., Goto, Atsushi, Gouda, Hebe N., Graetz, Nichola, Gugnani, Harish C., Gupta, Rahul, Gupta, Rajeev, Gutiérrez, Reyna A., Haagsma, Juanita, Hafezi-Nejad, Nima, Hagan, Holly, Halasa, Yara A., Hamadeh, Randah R., Hamavid, Hannah, Hammami, Mouhanad, Hancock, Jamie, Hankey, Graeme J., Hansen, Gillian M., Hao, Yuantao, Harb, Hilda L., Haro, Josep Maria, Havmoeller, Rasmu, Hay, Simon I., Hay, Roderick J., Heredia-Pi, Ileana B., Heuton, Kyle R., Heydarpour, Pouria, Higashi, Hideki, Hijar, Martha, Hoek, Hans W., Hoffman, Howard J., Hosgood, H Dean, Hossain, Mazeda, Hotez, Peter J., Hoy, Damian G., Hsairi, Mohamed, Hu, Guoqing, Huang, Cheng, Huang, John J., Husseini, Abdullatif, Huynh, Chantal, Iannarone, Marissa L., Iburg, Kim M., Innos, Kaire, Inoue, Manami, Islami, Farhad, Jacobsen, Kathryn H., Jarvis, Deborah L., Jassal, Simerjot K., Jee, Sun Ha, Jeemon, Panniyammakal, Jensen, Paul N., Jha, Vivekanand, Jiang, Guohong, Jiang, Ying, Jonas, Jost B., Juel, Knud, Kan, Haidong, Karch, André, Karema, Corine K., Karimkhani, Chante, Karthikeyan, Ganesan, Kassebaum, Nicholas J., Kaul, Anil, Kawakami, Norito, Kazanjan, Konstantin, Kemp, Andrew H., Kengne, Andre P., Keren, Andre, Khader, Yousef S., Khalifa, Shams Eldin A., Khan, Ejaz A., Khan, Gulfaraz, Khang, Young-Ho, Kieling, Christian, Kim, Daniel, Kim, Sungroul, Kim, Yunjin, Kinfu, Yohanne, Kinge, Jonas M., Kivipelto, Miia, Knibbs, Luke D., Knudsen, Ann Kristin, Kokubo, Yoshihiro, Kosen, Soewarta, Krishnaswami, Sanjay, Defo, Barthelemy Kuate, Bicer, Burcu Kucuk, Kuipers, Ernst J., Kulkarni, Chanda, Kulkarni, Veena S., Kumar, G Anil, Kyu, Hmwe H., Lai, Taavi, Lalloo, Ratilal, Lallukka, Tea, Lam, Hilton, Lan, Qing, Lansingh, Van C., Larsson, Ander, Lawrynowicz, Alicia E. B., Leasher, Janet L., Leigh, Jame, Leung, Ricky, Levitz, Carly E., Li, Bin, Li, Yichong, Li, Yongmei, Lim, Stephen S., Lind, Maggie, Lipshultz, Steven E., Liu, Shiwei, Liu, Yang, Lloyd, Belinda K., Lofgren, Katherine T., Logroscino, Giancarlo, Looker, Katharine J., Lortet-Tieulent, Joannie, Lotufo, Paulo A., Lozano, Rafael, Lucas, Robyn M., Lunevicius, Raimunda, Lyons, Ronan A., Ma, Stefan, Macintyre, Michael F., Mackay, Mark T., Majdan, Marek, Malekzadeh, Reza, Marcenes, Wagner, Margolis, David J., Margono, Christopher, Marzan, Melvin B., Masci, Joseph R., Mashal, Mohammad T., Matzopoulos, Richard, Mayosi, Bongani M., Mazorodze, Tasara T., Mcgill, Neil W., Mcgrath, John J., Mckee, Martin, Mclain, Abigail, Meaney, Peter A., Medina, Catalina, Mehndiratta, Man Mohan, Mekonnen, Wubegzier, Melaku, Yohannes A., Meltzer, Michele, Memish, Ziad A., Mensah, George A., Meretoja, Atte, Mhimbira, Francis A., Micha, Renata, Miller, Ted R., Mills, Edward J., Mitchell, Philip B., Mock, Charles N., Ibrahim, Norlinah Mohamed, Mohammad, Karzan A., Mokdad, Ali H., Mola, Glen L. D., Monasta, Lorenzo, Hernandez, Julio C. Montañez, Montico, Marcella, Montine, Thomas J., Mooney, Meghan D., Moore, Ami R., Moradi-Lakeh, Maziar, Moran, Andrew E., Mori, Rintaro, Moschandreas, Joanna, Moturi, Wilkister N., Moyer, Madeline L., Mozaffarian, Dariush, Msemburi, William T., Mueller, Ulrich O., Mukaigawara, Mitsuru, Mullany, Erin C., Murdoch, Michele E., Murray, Joseph, Murthy, Kinnari S., Naghavi, Mohsen, Naheed, Aliya, Naidoo, Kovin S., Naldi, Luigi, Nand, Devina, Nangia, Vinay, Narayan, K M. Venkat, Nejjari, Chakib, Neupane, Sudan P., Newton, Charles R., Ng, Marie, Ngalesoni, Frida N., Nguyen, Grant, Nisar, Muhammad I., Nolte, Sandra, Norheim, Ole F., Norman, Rosana E., Norrving, Bo, Nyakarahuka, Luke, Oh, In-Hwan, Ohkubo, Takayoshi, Ohno, Summer L., Olusanya, Bolajoko O., Opio, John Nelson, Ortblad, Katrina, Ortiz, Alberto, Pain, Amanda W., Pandian, Jeyaraj D., Panelo, Carlo Irwin A., Papachristou, Christina, Park, Eun-Kee, Park, Jae-Hyun, Patten, Scott B., Patton, George C., Paul, Vinod K., Pavlin, Boris I., Pearce, Neil, Pereira, David M., Perez-Padilla, Rogelio, Perez-Ruiz, Fernando, Perico, Norberto, Pervaiz, Aslam, Pesudovs, Konrad, Peterson, Carrie B., Petzold, Max, Phillips, Michael R., Phillips, Bryan K., Phillips, David E., Piel, Frédéric B., Plass, Dietrich, Poenaru, Dan, Polinder, Suzanne, Pope, Daniel, Popova, Svetlana, Poulton, Richie G., Pourmalek, Farshad, Prabhakaran, Dorairaj, Prasad, Noela M., Pullan, Rachel L., Qato, Dima M., Quistberg, D Alex, Rafay, Anwar, Rahimi, Kazem, Rahman, Sajjad U., Raju, Murugesan, Rana, Saleem M., Razavi, Homie, Reddy, K Srinath, Refaat, Amany, Remuzzi, Giuseppe, Resnikoff, Serge, Ribeiro, Antonio L., Richardson, Lee, Richardus, Jan Hendrik, Roberts, D Allen, Rojas-Rueda, David, Ronfani, Luca, Roth, Gregory A., Rothenbacher, Dietrich, Rothstein, David H., Rowley, Jane T., Roy, Nobhojit, Ruhago, George M., Saeedi, Mohammad Y., Saha, Sukanta, Sahraian, Mohammad Ali, Sampson, Uchechukwu K. A., Sanabria, Juan R., Sandar, Logan, Santos, Itamar S., Satpathy, Maheswar, Sawhney, Monika, Scarborough, Peter, Schneider, Ione J., Schöttker, Ben, Schumacher, Austin E., Schwebel, David C., Scott, James G., Seedat, Soraya, Sepanlou, Sadaf G., Serina, Peter T., Servan-Mori, Edson E., Shackelford, Katya A., Shaheen, Amira, Shahraz, Saeid, Levy, Teresa Shamah, Shangguan, Siyi, She, Jun, Sheikhbahaei, Sara, Shi, Peilin, Shibuya, Kenji, Shinohara, Yukito, Shiri, Rahman, Shishani, Kawkab, Shiue, Ivy, Shrime, Mark G., Sigfusdottir, Inga D., Silberberg, Donald H., Simard, Edgar P., Sindi, Shireen, Singh, Abhishek, Singh, Jasvinder A., Singh, Lavanya, Skirbekk, Vegard, Slepak, Erica Leigh, Sliwa, Karen, Soneji, Samir, Søreide, Kjetil, Soshnikov, Sergey, Sposato, Luciano A., Sreeramareddy, Chandrashekhar T., Stanaway, Jeffrey D., Stathopoulou, Vasiliki, Stein, Dan J., Stein, Murray B., Steiner, Caitlyn, Steiner, Timothy J., Stevens, Antony, Stewart, Andrea, Stovner, Lars J., Stroumpoulis, Konstantino, Sunguya, Bruno F., Swaminathan, Soumya, Swaroop, Mamta, Sykes, Bryan L., Tabb, Karen M., Takahashi, Ken, Tandon, Nikhil, Tanne, David, Tanner, Marcel, Tavakkoli, Mohammad, Taylor, Hugh R., Te Ao, Braden J., Tediosi, Fabrizio, Temesgen, Awoke M., Templin, Tara, Ten Have, Margreet, Tenkorang, Eric Y., Terkawi, Abdullah S., Thomson, Blake, Thorne-Lyman, Andrew L., Thrift, Amanda G., Thurston, George D., Tillmann, Taavi, Tonelli, Marcello, Topouzis, Foti, Toyoshima, Hideaki, Traebert, Jefferson, Tran, Bach X., Trillini, Matia, Truelsen, Thoma, Tsilimbaris, Miltiadi, Tuzcu, Emin M., Uchendu, Uche S., Ukwaja, Kingsley N., Undurraga, Eduardo A., Uzun, Selen B., Van Brakel, Wim H., Van De Vijver, Steven, Van Gool, Coen H., Van Os, Jim, Vasankari, Tommi J., Venketasubramanian, N, Violante, Francesco S., Vlassov, Vasiliy V., Vollset, Stein Emil, Wagner, Gregory R., Wagner, Joseph, Waller, Stephen G., Wan, Xia, Wang, Haidong, Wang, Jianli, Wang, Linhong, Warouw, Tati S., Weichenthal, Scott, Weiderpass, Elisabete, Weintraub, Robert G., Wenzhi, Wang, Werdecker, Andrea, Westerman, Ronny, Whiteford, Harvey A., Wilkinson, James D., Williams, Thomas N., Wolfe, Charles D., Wolock, Timothy M., Woolf, Anthony D., Wulf, Sarah, Wurtz, Brittany, Xu, Gelin, Yan, Lijing L., Yano, Yuichiro, Ye, Pengpeng, Yentür, Gökalp K., Yip, Paul, Yonemoto, Naohiro, Yoon, Seok-Jun, Younis, Mustafa Z., Yu, Chuanhua, Zaki, Maysaa E., Zhao, Yong, Zheng, Yingfeng, Zonies, David, Zou, Xiaonong, Salomon, Joshua A., Lopez, Alan D., Vos, Theo, Medische Sociologie, MUMC+: Hersen en Zenuw Centrum (3), MUMC+: MA Psychiatrie (3), Psychiatrie & Neuropsychologie, Barber, Ryan M, Foreman, Kyle J, Abd Allah, Foad, Abera, Semaw F, Abraham, Jerry P, Abu Raddad, Laith J, Abu Rmeileh, Niveen M, Ackerman, Ilana N, Adou, Arsène K, Adsuar, José C, Agardh, Emilie E, Albittar, Mohammed I, Alegretti, Miguel A, Alemu, Zewdie A, Alfonso Cristancho, Rafael, Almazroa, Mohammad A, Alvis Guzman, Nelson, Amare, Azmeraw T, Ameh, Emmanuel A, Anderson, Benjamin O, Antonio, Carl Abelardo T, Asghar, Rana J, Atkins, Lydia S, Avila, Marco A, Bachman, Victoria F, Bahit, Maria C, Barker Collo, Suzanne L, Barrero, Lope H, Basulaiman, Mohammed O, Bell, Michelle L, Bennett, Derrick A, Bensenor, Isabela M, Bertozzi Villa, Amelia, Beyene, Tariku J, Bhutta, Zulfiqar A, Blore, Jed D, Blosser, Christopher D, Blyth, Fiona M, Bohensky, Megan A, Bolliger, Ian W, Bornstein, Natan M, Bourne, Rupert R. A, Boyers, Lindsay N, Brayne, Carol E, Breitborde, Nicholas J. K, Briggs, Adam D, Brooks, Peter M, Brown, Jonathan C, Brugha, Traolach S, Buckle, Geoffrey C, Budke, Christine M, Bulloch, Andrew G, Campos Nonato, Ismael R, Carapetis, Jonathan R, Carpenter, David O, Castañeda Orjuela, Carlos A, Castro, Ruben E, Catalá López, Ferrán, Chadha, Vineet K, Chang, Jung Chen, Charlson, Fiona J, Chiang, Peggy P, Chimed Ochir, Odgerel, Christophi, Costas A, Coates, Matthew M, Coffeng, Luc E, Coggeshall, Megan S, Colquhoun, Samantha M, Cooke, Graham S, Cooper, Leslie T, Coppola, Luis M, Criqui, Michael H, Crump, John A, Cuevas Nasu, Lucia, Dargan, Paul I, Davitoiu, Dragos V, Del Pozo Cruz, Borja, Dellavalle, Robert P, Jarlais, Don C. De, Dharmaratne, Samath D, Dherani, Mukesh K, Diaz Torné, Cesar, Ding, Eric L, Dorsey, E. Ray, Driscoll, Tim R, Duber, Herbert C, Ebel, Beth E, Edmond, Karen M, Elshrek, Yousef M, Ermakov, Sergey P, Erskine, Holly E, Faraon, Emerito Jose A, Fay, Derek F, Feigin, Valery L, Felson, David T, Fereshtehnejad, Seyed Mohammad, Fernandes, Jefferson G, Ferrari, Alize J, Flaxman, Abraham D, Fleming, Thomas D, Forouzanfar, Mohammad H, Fowkes, F. Gerry R, Paleo, Urbano Fra, Franklin, Richard C, Gankpé, Fortuné G, Geleijnse, Johanna M, Gessner, Bradford D, Gibney, Katherine B, González Medina, Diego, Gosselin, Richard A, Gotay, Carolyn C, Gouda, Hebe N, Gugnani, Harish C, Gutiérrez, Reyna A, Hafezi Nejad, Nima, Halasa, Yara A, Hamadeh, Randah R, Hankey, Graeme J, Hansen, Gillian M, Harb, Hilda L, Hay, Simon I, Hay, Roderick J, Heredia Pi, Ileana B, Heuton, Kyle R, Hoek, Hans W, Hoffman, Howard J, Hosgood, H. Dean, Hotez, Peter J, Hoy, Damian G, Huang, John J, Iannarone, Marissa L, Iburg, Kim M, Jacobsen, Kathryn H, Jarvis, Deborah L, Jassal, Simerjot K, Jensen, Paul N, Jonas, Jost B, Karema, Corine K, Kassebaum, Nicholas J, Kemp, Andrew H, Kengne, Andre P, Khader, Yousef S, Khalifa, Shams Eldin A, Khan, Ejaz A, Khang, Young Ho, Kinge, Jonas M, Knibbs, Luke D, Kuipers, Ernst J, Kulkarni, Veena S, Kumar, G. Anil, Kyu, Hmwe H, Lansingh, Van C, Lawrynowicz, Alicia E. B, Leasher, Janet L, Levitz, Carly E, Lim, Stephen S, Lipshultz, Steven E, Lloyd, Belinda K, Lofgren, Katherine T, Looker, Katharine J, Lortet Tieulent, Joannie, Lotufo, Paulo A, Lucas, Robyn M, Lyons, Ronan A, Macintyre, Michael F, Mackay, Mark T, Margolis, David J, Marzan, Melvin B, Masci, Joseph R, Mashal, Mohammad T, Mayosi, Bongani M, Mazorodze, Tasara T, Mcgill, Neil W, Mcgrath, John J, Meaney, Peter A, Melaku, Yohannes A, Memish, Ziad A, Mensah, George A, Mhimbira, Francis A, Miller, Ted R, Mills, Edward J, Mitchell, Philip B, Mock, Charles N, Mohammad, Karzan A, Mokdad, Ali H, Mola, Glen L. D, Montine, Thomas J, Mooney, Meghan D, Moore, Ami R, Moradi Lakeh, Maziar, Moran, Andrew E, Moturi, Wilkister N, Moyer, Madeline L, Msemburi, William T, Mueller, Ulrich O, Mullany, Erin C, Murdoch, Michele E, Murthy, Kinnari S, Naidoo, Kovin S, Narayan, K. M. Venkat, Neupane, Sudan P, Newton, Charles R, Ngalesoni, Frida N, Nisar, Muhammad I, Norheim, Ole F, Norman, Rosana E, Oh, In Hwan, Ohno, Summer L, Olusanya, Bolajoko O, Pain, Amanda W, Pandian, Jeyaraj D, Panelo, Carlo Irwin A, Park, Eun Kee, Park, Jae Hyun, Patten, Scott B, Patton, George C, Paul, Vinod K, Pavlin, Boris I, Pereira, David M, Perez Padilla, Rogelio, Perez Ruiz, Fernando, Peterson, Carrie B, Phillips, Michael R, Phillips, Bryan K, Phillips, David E, Piel, Frédéric B, Poulton, Richie G, Prasad, Noela M, Pullan, Rachel L, Qato, Dima M, Quistberg, D. Alex, Rahman, Sajjad U, Rana, Saleem M, Reddy, K. Srinath, Ribeiro, Antonio L, Roberts, D. Allen, Rojas Rueda, David, Roth, Gregory A, Rothstein, David H, Rowley, Jane T, Ruhago, George M, Saeedi, Mohammad Y, Sampson, Uchechukwu K. A, Sanabria, Juan R, Santos, Itamar S, Schneider, Ione J, Schumacher, Austin E, Schwebel, David C, Scott, James G, Sepanlou, Sadaf G, Serina, Peter T, Servan Mori, Edson E, Shackelford, Katya A, Shrime, Mark G, Sigfusdottir, Inga D, Silberberg, Donald H, Simard, Edgar P, Singh, Jasvinder A, Sposato, Luciano A, Sreeramareddy, Chandrashekhar T, Stanaway, Jeffrey D, Stein, Dan J, Stein, Murray B, Steiner, Timothy J, Stovner, Lars J, Sunguya, Bruno F, Sykes, Bryan L, Tabb, Karen M, Taylor, Hugh R, Ao, Braden J. Te, Temesgen, Awoke M, Tenkorang, Eric Y, Terkawi, Abdullah S, Thorne Lyman, Andrew L, Thrift, Amanda G, Thurston, George D, Tran, Bach X, Tuzcu, Emin M, Uchendu, Uche S, Ukwaja, Kingsley N, Undurraga, Eduardo A, Uzun, Selen B, Van Brakel, Wim H, van Gool, Coen H, Vasankari, Tommi J, Violante, Francesco S, Vlassov, Vasiliy V, Wagner, Gregory R, Waller, Stephen G, Warouw, Tati S, Weintraub, Robert G, Whiteford, Harvey A, Wilkinson, James D, Williams, Thomas N, Wolfe, Charles D, Wolock, Timothy M, Woolf, Anthony D, Yan, Lijing L, Yentür, Gökalp K, Yoon, Seok Jun, Younis, Mustafa Z, Zaki, Maysaa E, Salomon, Joshua A, Lopez, Alan D, Computational Science and Engineering Department [Daresbury] ( STFC ), Science & Technologie Facilities Council, Neuroépidémiologie Tropicale ( NET ), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST ), Université de Limoges ( UNILIM ) -Université de Limoges ( UNILIM ), Service de Chirurgie Thoracique et Vasculaire - Médecine vasculaire [CHU Limoges], CHU Limoges, Weill Cornell Medical College - Qatar, Qatar Foundation - Education City, Doha, Maladies chroniques, santé perçue, et processus d'adaptation ( APEMAC ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université de Lorraine ( UL ), Centre d'Investigation Clinique - Epidemiologie Clinique/essais Cliniques Nancy, Cancéropôle du Grand Est-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Karolinska Institute, karolinska institute, Centro de Estudios Avanzados en Zonas Aridas ( CEAZA ), Ecole Polytechnique Fédérale de Lausanne ( EPFL ), Wisconsin Division of Public Health, Regional Genetic Service, St Mary's Hospital, Manchester, Laboratoire d'Ingénierie des Matériaux ( LIM ), Centre National de la Recherche Scientifique ( CNRS ), Computer Science Department [Bristol], University of Bristol [Bristol], Lawrence Berkeley National Laboratory [Berkeley] ( LBNL ), Samsung Research &Development Institute India - Bangalore (Groupe Samsung) ( SRI-B ), Multimedia Research Center ( MRC ), University of Alberta [Edmonton], Division of Biostatistics ( Biostat - MINNEAPOLIS ), University of Minnesota [Minneapolis], Laboratory of Neurologic Diseases, Mario Negri Institute, Milan, University of Southampton [Southampton], Imperial College London, Neurology Department, Ichilov Medical Center, Department of Public Health and Primary Care, Cambridge University, Interactions, transferts, ruptures artistiques et culturels - EA 6301 ( InTRu ), Université de Tours, Institut Jacques Monod ( IJM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Institute of Parasitology, STAR laboratory, Stanford University [Stanford], Unité de recherche Virologie et Immunologie Moléculaires ( VIM ), Institut National de la Recherche Agronomique ( INRA ), Tennent Institute of Ophthalmology, National University of Singapore ( NUS ), Multidisciplinary Nanotechnology Centre, Swansea University, Department of Computer Sciences [Scheffield], University of Sheffield [Sheffield], Cyprus International Institute for the Environment and Public Health, Harvard School of Public Health, Glasgow Centre for Physical Organic Chemistry, University of Glasgow, King‘s College London, Université Panthéon-Sorbonne - UFR Science Politique ( UP1 UFR11 ), Université Panthéon-Sorbonne ( UP1 ), National Diagnostics Centre ( NDC ), National University of Ireland [Galway] ( NUI Galway ), Arthritis Research UK Epidemiology Unit ( MANCHESTER - Arthritis Research ), University of Manchester [Manchester], CEGOT - Porto, Universidade do Porto [Porto], Advanced Laboratories on Embedded Systems [Roma] ( ALES ), Department of Biology [Miami], University of Miami [Coral Gables], Division of Human Nutrition, Wageningen University and Research Centre [Wageningen] ( WUR ), Spatial Ecology and Epidemiology Group, University of Oxford [Oxford], Department of Civil Engineering [Hamirpur], National Institute of Technology [Hamirpur], GEMMA — Environmental Engineering and Microbiology Research Group, Department of Hydraulic, Maritime and Environmental Engineering, Universitat Politècnica de Catalunya [Barcelona] ( UPC ), Institut National de Recherche et d'Analyse Physico-Chimique ( INRAP ), Institut National de Recherche et d'Analyse Physico-chimique (INRAP-Tunisie), University of Connecticut ( UCONN ), Norwegian Institute for Air Research ( NILU ), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) ( FEMTO-ST ), Université de Franche-Comté ( UFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Ecole Nationale Supérieure de Mécanique et des Microtechniques ( ENSMM ) -Université de Technologie de Belfort-Montbeliard ( UTBM ), Tehran University, Friedrich-Alexander Universität Erlangen-Nürnberg ( FAU ), Secretariat of the Pacific Community, Public Health Division, Sociétés, Acteurs, Gouvernement en Europe ( SAGE ), Université de Strasbourg ( UNISTRA ) -Centre National de la Recherche Scientifique ( CNRS ), School of Physics and Astronomy, Washington State University ( WSU ), Laboratoire de Physique de l'ENS Lyon ( Phys-ENS ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Institut de recherche en informatique de Toulouse ( IRIT ), Institut National Polytechnique [Toulouse] ( INP ) -Université Toulouse 1 Capitole ( UT1 ) -Université Toulouse - Jean Jaurès ( UT2J ) -Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique ( CNRS ), School of Computer Science - China University of Geosciences (China University of Geosciences (East Area)), Université Catholique de Louvain ( UCL ), Div Cyclotron & Radiopharmaceut Sci ( DRDO, INMAS ), Univ New Delhi, University of St Andrews [Scotland], University of Cape Town, Department of Neuroscience, Karolinska Institutet [Stockholm], Institut de Physique Nucléaire d'Orsay ( IPNO ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Centre National de la Recherche Scientifique ( CNRS ), Department of Computer Science and Engineering [Daejeon] (Chungnam National University), Lawrence University, Gastroenterology & Hepatology, Tata Research Development and Design Center ( TRDDC ), TCS Innovation Labs, Laboratoire MOLTECH-Anjou [Angers] ( MOLTECH ANJOU ), Université d'Angers ( UA ) -Centre National de la Recherche Scientifique ( CNRS ), University of Helsinki [Helsinki], Google Inc [Mountain View], Research at Google, Swedish Defense Research Agency ( FOI ), Centre de Recherche en Information Biomédicale sino-français ( CRIBS ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Southeast University [Jiangsu]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratory of Image Science and Technology [Nanjing] ( LIST ), Southeast University [Jiangsu]-School of Computer Science and Engineering, Laboratoire de glaciologie et géophysique de l'environnement ( LGGE ), Observatoire des Sciences de l'Univers de Grenoble ( OSUG ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut national des sciences de l'Univers ( INSU - CNRS ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut national des sciences de l'Univers ( INSU - CNRS ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Centre National de la Recherche Scientifique ( CNRS ), School of Business and Informatics, University of Boras, Department of Mechanical and Automation Engineering ( CAD Laboratory ), The Chinese University of Hong Kong [Hong Kong], Università degli studi di Bari, Heuristique et Diagnostic des Systèmes Complexes [Compiègne] ( Heudiasyc ), Université de Technologie de Compiègne ( UTC ) -Centre National de la Recherche Scientifique ( CNRS ), Department of plant pathology and microbiology - centre for sustainable pest and disease management, Rothamsted Research, RGU, Department of Rheumatology and Connective Tissue Diseases, Medical University of Lublin, Barts and The London School of Medicine and Dentistry, Queen Mary University of London ( QMUL ), Centre d'économie de la Sorbonne ( CES ), Université Panthéon-Sorbonne ( UP1 ) -Centre National de la Recherche Scientifique ( CNRS ), Paris School of Economics ( PSE ), Istituto Dalle Molle di Studi sull'Intelligenza Artificiale ( IDSIA ), Università della Svizzera italiana ( USI ) -Scuola universitaria professionale della Svizzera italiana [Manno] ( SUPSI ), Anaesthetics, Southampton University Hospital, Department of Mathematics, University of Iowa [Iowa City], College of Medicine, Alfaisal University, Saudi Ministry of Health, Institut national des recherches agricoles du Bénin, Centre de Recherches agricoles du Sud, Departments of Epidemiology and Nutrition, Unit of Human Nutrition, Agricultural University of Athens, Department of Animal Science, PennState University [Pennsylvania] ( PSU ), University of Virginia, University of Virginia [Charlottesville], Epidemiology and Biostatistics Unit, Institute for Maternal and Child Health - IRCCS ‘‘Burlo Garofolo', Jet Propulsion Laboratory ( JPL ), NASA-California Institute of Technology ( CALTECH ), Division of Cardiovascular Medicine and Channing Division of Network Medicine, Brigham and Women's Hospital [Boston], Division of Gastroenterology and Hepatology, Department of Immunology, Mayo Clinic, Department of Chemistry, Scientific Computing Research Unit, Department of dermatology, Milano University-Azienda Ospedaleria Ospedali Riuniti di Bergamo, Department of epidemiology and Public Health, Faculty of Medicine, Hong Kong Baptist University ( HKBU ), Département Optique ( OPT ), Université européenne de Bretagne ( UEB ) -Télécom Bretagne-Institut Mines-Télécom [Paris], Department of Neurology Lunds University Hospital Lund, Services répartis, Architectures, MOdélisation, Validation, Administration des Réseaux ( SAMOVAR ), Institut Mines-Télécom [Paris]-Télécom SudParis ( TSP ) -Centre National de la Recherche Scientifique ( CNRS ), Département Réseaux et Services Multimédia Mobiles ( RS2M ), Institut Mines-Télécom [Paris]-Télécom SudParis ( TSP ), Electrical Engineering and Computer Science Department - Case Western Reserve University, Case Western Reserve University [Cleveland], Institut Lumière Matière [Villeurbanne] ( ILM ), Université Claude Bernard Lyon 1 ( UCBL ), World Health Organization, Nordic School of Public Health, The James Hutton Institute, Sero, Sero consulting, Evolutionary Ecology of Infectious Disease Group, Department of Zoology, Horia Hulubei National Institute for Physics and Nuclear Engineering, Dunedin School of Medicine, University of Otago, Department of Physics, Clarendon Laboratory, Center for TeleInFrastruktur ( CTIF ), Aalborg University [Denmark] ( AAU ), Physikalisches Institut [Freiburg], Albert-Ludwigs-Universität Freiburg, Savoirs, Textes, Langage (STL) - UMR 8163 ( STL ), Université de Lille-Centre National de la Recherche Scientifique ( CNRS ), Dept.of Computer Science, Indian Institute of Technology Madras ( IIT Madras ), Istituto Mario Negri Bergamo, Centro Ricerche e Trapianti Villa Camozzi, Universidade Estadual Paulista Júlio de Mesquita ( UNESP ), Department of Public Health, Erasmus MC-University Medical Center Rotterdam, Université Grenoble Alpes - UFR Médecine ( UGA UFRM ), Université Grenoble Alpes ( UGA ), Clinical Epidemiology and Aging Research, German Cancer Research Center, Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Symantec, European Microsoft Innovation Center ( EMIC ), Microsoft Corporation [Redmond, Wash.], Laboratoire de Mécanique, Physique et Géosciences ( LMPG ), Université Le Havre Normandie ( ULH ), Normandie Université ( NU ) -Normandie Université ( NU ), Novartis institute for tropical diseases, Institut de Génétique et de Biologie Moléculaire et Cellulaire ( IGBMC ), Université de Strasbourg ( UNISTRA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Departments of Anatomy and Cell Biology, Wayne State University School of Medicine, Departments of Ophthalmology, Departments of Applied Physics [New Haven], Yale University [New Haven], Center for Mathematical Modeling ( CMM ), Universidad de Santiago de Chile [Santiago] ( USACH ), Laboratory for Atmospheric and Space Physics [Boulder] ( LASP ), University of Colorado Boulder [Boulder], University of Occupational and Environmental Health [Kitakyushu] ( UEOH ), Department of Computer Science and Engineering [New Delhi], Indian Institute of Technology Delhi ( IIT Delhi ), Institut de Recherche sur les Phénomènes Hors Equilibre ( IRPHE ), Aix Marseille Université ( AMU ) -Ecole Centrale de Marseille ( ECM ) -Centre National de la Recherche Scientifique ( CNRS ), GlaxoSmithKline, Imperial College London-Clinical Imaging Center, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, Yale School of Medicine-Yale School of Medicine-Yale Stem Cell Center, Maclean Building, Benson Lane, Crowmarsh Gifford, Centre for Ecology and Hydrology, Nanoscience Institute ( NEST ), Dipartimento di Fisica, Università di Pisa, Aristotle University of Thessaloniki, Laboratory Of Immune Cell Biology ( LICB ), National Institutes of Health ( NIH ), Institute of Human Genetics, Bonn Universität [Bonn], Occupational Health Unit, Bologna University Hospital-Sant'Orsola-Malpighi Polyclinic, Royal Institute of Technology [Stockholm] ( KTH ), Institut für Informatik [München/Munich] ( LMU ), Ludwig-Maximilians-Universität München, NICTA [Eveleigh], National ICT Australia [Sydney] ( NICTA ), Manchester Academic Health Sciences Centre, Institut d'Histoire et de Philosophie des Sciences et des Techniques ( IHPST ), Université Panthéon-Sorbonne ( UP1 ) -Département d'Etudes Cognitives - ENS Paris ( DEC ), École normale supérieure - Paris ( ENS Paris ) -École normale supérieure - Paris ( ENS Paris ) -Centre National de la Recherche Scientifique ( CNRS ), Ghent University [Belgium] ( UGENT ), German Research Centre for Geosciences - Helmholtz-Centre Potsdam ( GFZ ), Laboratoire de recherche en Hydrodynamique, Énergétique et Environnement Atmosphérique ( LHEEA ), École Centrale de Nantes ( ECN ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Recherche en Génie Civil et Mécanique ( GeM ), Université de Nantes ( UN ) -École Centrale de Nantes ( ECN ) -Centre National de la Recherche Scientifique ( CNRS ), Neurorestoration Group, King‘s College London-Wolfson Centre for Age-related Diseases, Department of Computer Science [KAIST] ( CS ), Korea Advanced Institute of Science and Technology ( KAIST ), Laboratoire de l'Accélérateur Linéaire ( LAL ), Natl Engn Res Ctr Vegetables, Key Lab Biol & Genet Improvement Hort Crops N Chi, Beijing Acad Agr & Forestry Sci, University Hospital Puerta de Hierro, Madrid, Computational Science and Engineering Department [Daresbury] (STFC), Neuroépidémiologie Tropicale (NET), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Weill Cornell Medicine [Qatar], Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Cancéropôle du Grand Est-Institut National de la Santé et de la Recherche Médicale (INSERM), Centro de Estudios Avanzados en Zonas Aridas (CEAZA), Ecole Polytechnique Fédérale de Lausanne (EPFL), Laboratoire d'Ingénierie des Matériaux (LIM), Centre National de la Recherche Scientifique (CNRS), Lawrence Berkeley National Laboratory [Berkeley] (LBNL), Samsung Research &Development Institute India - Bangalore (Groupe Samsung) (SRI-B), Multimedia Research Center (MRC), University of Alberta, Division of Biostatistics (Biostat - MINNEAPOLIS), University of Minnesota [Twin Cities] (UMN), University of Minnesota System-University of Minnesota System, University of Southampton, University of Cambridge [UK] (CAM), Interactions, transferts, ruptures artistiques et culturels - EA 6301 (InTRu), Université de Tours (UT), Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Stanford University, Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Institut National de la Recherche Agronomique (INRA), National University of Singapore (NUS), Université Paris 1 Panthéon-Sorbonne - UFR Science Politique (UP1 UFR11), Université Paris 1 Panthéon-Sorbonne (UP1), National Diagnostics Centre (NDC), National University of Ireland [Galway] (NUI Galway), Arthritis Research UK Epidemiology Unit (MANCHESTER - Arthritis Research), Universidade do Porto = University of Porto, Advanced Laboratories on Embedded Systems [Roma] (ALES), Wageningen University and Research [Wageningen] (WUR), University of Oxford, Universitat Politècnica de Catalunya [Barcelona] (UPC), Institut National de Recherche et d'Analyse Physico-Chimique (INRAP), University of Connecticut (UCONN), Norwegian Institute for Air Research (NILU), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), University of Tehran, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Sociétés, Acteurs, Gouvernement en Europe (SAGE), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), The George Washington University (GW), Washington State University (WSU), Laboratoire de Physique de l'ENS Lyon (Phys-ENS), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut de recherche en informatique de Toulouse (IRIT), Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Université Catholique de Louvain = Catholic University of Louvain (UCL), Div Cyclotron & Radiopharmaceut Sci (DRDO, INMAS), School of Physics and Astronomy [St Andrews], Tata Research Development and Design Center (TRDDC), MOLTECH-Anjou, Université d'Angers (UA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Swedish Defense Research Agency (FOI), Centre de Recherche en Information Biomédicale sino-français (CRIBS), Université de Rennes (UR)-Southeast University [Jiangsu]-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratory of Image Science and Technology [Nanjing] (LIST), Laboratoire de glaciologie et géophysique de l'environnement (LGGE), Observatoire des Sciences de l'Univers de Grenoble (OSUG), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut national des sciences de l'Univers (INSU - CNRS)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut national des sciences de l'Univers (INSU - CNRS)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Department of Mechanical and Automation Engineering (CAD Laboratory), Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Heuristique et Diagnostic des Systèmes Complexes [Compiègne] (Heudiasyc), Université de Technologie de Compiègne (UTC)-Centre National de la Recherche Scientifique (CNRS), Biotechnology and Biological Sciences Research Council (BBSRC)-Biotechnology and Biological Sciences Research Council (BBSRC), Queen Mary University of London (QMUL), Centre d'économie de la Sorbonne (CES), Université Paris 1 Panthéon-Sorbonne (UP1)-Centre National de la Recherche Scientifique (CNRS), Paris School of Economics (PSE), Université Paris 1 Panthéon-Sorbonne (UP1)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École des hautes études en sciences sociales (EHESS)-École des Ponts ParisTech (ENPC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Istituto Dalle Molle di Studi sull'Intelligenza Artificiale (IDSIA), Università della Svizzera italiana = University of Italian Switzerland (USI)-Scuola universitaria professionale della Svizzera italiana = University of Applied Sciences and Arts of Southern Switzerland [Manno] (SUPSI), Pennsylvania State University (Penn State), Penn State System-Penn State System, Jet Propulsion Laboratory (JPL), NASA-California Institute of Technology (CALTECH), Hong Kong Baptist University (HKBU), Département Optique (OPT), Université européenne de Bretagne - European University of Brittany (UEB)-Télécom Bretagne-Institut Mines-Télécom [Paris] (IMT), Services répartis, Architectures, MOdélisation, Validation, Administration des Réseaux (SAMOVAR), Institut Mines-Télécom [Paris] (IMT)-Télécom SudParis (TSP), Département Réseaux et Services Multimédia Mobiles (TSP - RS2M), University of Melbourne, Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), University of Otago [Dunedin, Nouvelle-Zélande], Center for TeleInFrastruktur (CTIF), Aalborg University [Denmark] (AAU), Savoirs, Textes, Langage (STL) - UMR 8163 (STL), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Indian Institute of Technology Madras (IIT Madras), Universidade Estadual Paulista Júlio de Mesquita Filho = São Paulo State University (UNESP), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), European Microsoft Innovation Center (EMIC), Laboratoire de Mécanique, Physique et Géosciences (LMPG), Université Le Havre Normandie (ULH), Normandie Université (NU)-Normandie Université (NU), Novartis Institute for Tropical Diseases (NITD), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Center for Mathematical Modeling (CMM), Universidad de Chile = University of Chile [Santiago] (UCHILE), Laboratory for Atmospheric and Space Physics [Boulder] (LASP), University of Colorado [Boulder], University of Occupational and Environmental Health [Kitakyushu] (UEOH), Indian Institute of Technology Delhi (IIT Delhi), Institut de Recherche sur les Phénomènes Hors Equilibre (IRPHE), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Yale University [New Haven]-Yale School of Medicine [New Haven, Connecticut] (YSM), Nanoscience Institute (NEST), University of Pisa - Università di Pisa, Laboratory Of Immune Cell Biology (LICB), National Institutes of Health [Bethesda] (NIH), Rheinische Friedrich-Wilhelms-Universität Bonn, Royal Institute of Technology [Stockholm] (KTH ), Institut für Informatik [München/Munich] (LMU), Ludwig-Maximilians-Universität München (LMU), National ICT Australia [Sydney] (NICTA), Institut d'Histoire et de Philosophie des Sciences et des Techniques (IHPST), Université Paris 1 Panthéon-Sorbonne (UP1)-Département d'Etudes Cognitives - ENS Paris (DEC), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Universiteit Gent = Ghent University (UGENT), German Research Centre for Geosciences - Helmholtz-Centre Potsdam (GFZ), Laboratoire de recherche en Hydrodynamique, Énergétique et Environnement Atmosphérique (LHEEA), École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche en Génie Civil et Mécanique (GeM), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS), Department of Computer Science [KAIST] (CS), Korea Advanced Institute of Science and Technology (KAIST), Kardiyoloji, Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Minnesota [Twin Cities], Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Unité de recherche Virologie et Immunologie Moléculaires (VIM), Université Panthéon-Sorbonne - UFR Science Politique (UP1 UFR11), Université Panthéon-Sorbonne (UP1), Wageningen University and Research Centre [Wageningen] (WUR), Institut National de Recherche et d'Analyse Physico-chimique (Ariana, Tunisie) (INRAP), Université de Franche-Comté (UFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM), George Washington University (GW), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université Toulouse 1 Capitole (UT1)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, Université Catholique de Louvain (UCL), MOLTECH-ANJOU (MOLTECH-ANJOU), Université d'Angers (UA)-Centre National de la Recherche Scientifique (CNRS), University of Helsinki, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Southeast University [Jiangsu]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), Université Panthéon-Sorbonne (UP1)-Centre National de la Recherche Scientifique (CNRS), Università della Svizzera italiana (USI)-Scuola universitaria professionale della Svizzera italiana [Manno] (SUPSI), California Institute of Technology (CALTECH)-NASA, Institut Mines-Télécom [Paris] (IMT)-Télécom SudParis (TSP)-Centre National de la Recherche Scientifique (CNRS), Département Réseaux et Services Multimédia Mobiles (RS2M), Universidade Estadual Paulista Júlio de Mesquita Filho [São José do Rio Preto] (UNESP), Université Grenoble Alpes (UGA), Universidad de Santiago de Chile [Santiago] (USACH), Yale University [New Haven]-Yale University School of Medicine, Université Panthéon-Sorbonne (UP1)-Centre National de la Recherche Scientifique (CNRS)-Département d'Etudes Cognitives - ENS Paris (DEC), École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris), Ghent University [Belgium] (UGENT), Université de Nantes - Faculté des Sciences et des Techniques, Grelier, Elisabeth, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Universidade do Porto, Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Université Toulouse 1 Capitole (UT1), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire des Sciences de l'Univers de Grenoble (OSUG), Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Università degli studi di Bari Aldo Moro (UNIBA), École des Ponts ParisTech (ENPC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris 1 Panthéon-Sorbonne (UP1)-Centre National de la Recherche Scientifique (CNRS)-École des hautes études en sciences sociales (EHESS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Università della Svizzera italiana = University of Italian Switzerland (USI)-Scuola universitaria professionale della Svizzera italiana [Manno] (SUPSI), Institut Mines-Télécom [Paris] (IMT)-Télécom Bretagne-Université européenne de Bretagne - European University of Brittany (UEB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Universiteit Gent = Ghent University [Belgium] (UGENT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-CHU Limoges-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Technologie de Belfort-Montbeliard (UTBM), Institut de Chimie du CNRS (INC)-Université d'Angers (UA)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-École Centrale de Nantes (ECN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut national des sciences de l'Univers (INSU - CNRS)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), Wolfson Centre for Age-related Diseases-King‘s College London, Cell biology, Public Health, Epidemiology, Health Technology Assessment (HTA), Erasmus MC other, Pathology, and Cardiothoracic Surgery
Subjects: Gerontology, Male, CHANGING RELATION, Nutrition and Disease, MESH : Life Expectancy, MESH : Aged, ECONOMIC-DEVELOPMENT, Poison control, MESH: Global Health, Global Health, Socioeconomic Factor, Communicable Disease, MESH : Chronic Disease, Health Transition, Voeding en Ziekte, Quality-Adjusted Life Year, SELF-RATED HEALTH, MESH : Socioeconomic Factors, Medicine, MESH : Female, MESH: Mortality, Premature, 2. Zero hunger, MESH: Aged, education.field_of_study, MESH: Middle Aged, Mortality rate, Medicine (all), GBD2013 diseases, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, General Medicine, Middle Aged, 3. Good health, MESH : Wounds and Injuries, Epidemiological transition, MESH: Quality-Adjusted Life Years, MESH: Communicable Diseases, NONCOMMUNICABLE DISEASES, Female, Quality-Adjusted Life Years, MESH: Life Expectancy, MESH: Health Transition, Human, MESH: Socioeconomic Factors, ACUTE MYOCARDIAL-INFARCTION, MESH : Male, MORTALITY TRENDS, Population, MESH : Health Transition, Communicable Diseases, Article, Life Expectancy, EUROPEAN-UNION, SDG 3 - Good Health and Well-being, General & Internal Medicine, SYSTEMATIC ANALYSIS, Disability-adjusted life year, Humans, Life Science, MESH : Middle Aged, Mortality, education, Premature, MESH : Mortality, Premature, VLAG, Aged, MESH: Humans, business.industry, Mortality, Premature, MESH: Chronic Disease, MESH : Communicable Diseases, Wounds and Injurie, MESH : Humans, MESH : Quality-Adjusted Life Years, Non-communicable disease, Chronic Disease, Socioeconomic Factors, Wounds and Injuries, medicine.disease, MESH: Male, LOW SOCIOECONOMIC-STATUS, Years of potential life lost, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Wounds and Injuries, Life expectancy, RISK-FACTORS, MESH : Global Health, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH: Female, Demography
Abstract: Summary Background The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age–sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development. Methods We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time. Findings Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6–6·6), from 65·3 years (65·0–65·6) in 1990 to 71·5 years (71·0–71·9) in 2013, HALE at birth rose by 5·4 years (4·9–5·8), from 56·9 years (54·5–59·1) to 62·3 years (59·7–64·8), total DALYs fell by 3·6% (0·3–7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6–29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non–communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries. Interpretation Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition—in which increasing sociodemographic status brings structured change in disease burden—is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions. Funding Bill & Melinda Gates Foundation. BACKGROUND: The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age-sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development. METHODS: We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time. FINDINGS: Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6-6·6), from 65·3 years (65·0-65·6) in 1990 to 71·5 years (71·0-71·9) in 2013, HALE at birth rose by 5·4 years (4·9-5·8), from 56·9 years (54·5-59·1) to 62·3 years (59·7-64·8), total DALYs fell by 3·6% (0·3-7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6-29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non-communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries. INTERPRETATION: Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition-in which increasing sociodemographic status brings structured change in disease burden-is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions. FUNDING: Bill & Melinda Gates Foundation.
Published: 2015

31. Human plague: An old scourge that needs new answers

Author: Steven R. Belmain, Minoarisoa Rajerison, Oswaldo Cabanillas, Nils Chr. Stenseth, Peter Horby, Christian E. Demeure, Sandra Telfer, Xavier Vallès, Beza Ramasindrazana, Ratsitorahina M, Inès Vigan-Womas, Voahangy Andrianaivoarimanana, Pablo Tortosa, Yazdan Yazdanpanah, Laurence Baril, Javier Pizarro-Cerdá, David M. Wagner, Arnaud Fontanet, Eric D'Ortenzio, Jane Lynda Deuve, Romain Girod, Paul S. Mead, Holger C. Scholz, B. Joseph Hinnebusch, Guia Carrara, Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP), Centre for Ecological and Evolutionary Synthesis (CEES), Department of Biosciences [Oslo], Faculty of Mathematics and Natural Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Faculty of Mathematics and Natural Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Tsinghua University [Beijing] (THU), Yersinia, Institut Pasteur [Paris] (IP), University of Oxford, Centers for Disease Control and Prevention, Oficina General de Epidemiologia [Lima, Peru], Ministerio de Salud de Perú [Lima], Unité Peste - Plague Unit [Antananarivo, Madagascar], Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Bundeswehr Institute of Microbiology, Unité d'Entomologie Médicale [Antananarivo, Madagascar] (IPM), Rocky Mountain Laboratories, Unité d'immunologie des maladies infectieuses [Antananarivo, Madagascar] (IPM), Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Northern Arizona University [Flagstaff], University of Aberdeen, REACTing, Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Processus Infectieux en Milieu Insulaire Tropical (PIMIT), Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IRD-Centre National de la Recherche Scientifique (CNRS), Natural Resources Institute [Chatham], University of Greenwich, The workshop meeting where the contents of this article were developed was hosted by the Institut Pasteur (Paris, France) with financial and organizational support from the Department of International Affairs, the Emerging Disease Epidemiology Unit, the Mathematical Modelling of Infectious Diseases Unit and REACTing-Inserm. Oswaldo Cabanillas’s travel was financed by the Department of International Affairs at the Institut Pasteur (Paris, France). Travel costs for Laurence Baril and Maherisoa Ratsitorahina were financially supported by USAID (Grant n° AID-687-G-13-00003), and for Voahangy Andrianaivoarimanan and Minoarisoa Rajerison by Northern Arizona University (through HDTRA1-11-16-BRCWMD-BAA). Attendance of Steven Belmain was supported by the African Union (Grant AURGII/1/006/2016). Travel and accommodation for Feno Rakotoarimanana, and accommodation for Romain Girod, Beza Ramasindrazana, Voahangy Andrianaivoarimanana, and Minoarisoa Rajerison, were financially supported by the Wellcome Trust/UK Department for International Development (Grant 211309/Z/18/Z) and REACTing-Inserm. All other participants financially supported travel and accommodation through their own institutional funding. The preparation and editing of the manuscript was financially supported by Wellcome Trust/UK Department for International Development (Grant 211309/Z/18/Z)., List of the other participants to the Plague Workshop (by alphabetical order): Fabrice Biot, Institut de Recherche Biomédicale des Armées, France, Carine Brouat, IRD, France, Simon Cauchemez, Infectious Diseases Mathematical Modelling Unit, Institut Pasteur, Paris, France, Rob Cohen, USAID, Washington, DC, USA, Koussay Dellagy, Department of International Affairs, Institut Pasteur, Paris, France, Nathalie Denoyes, Institut Pasteur, Paris, France, Hebert Echenique-Rivera, Yersinia Unit, Institut Pasteur, Paris, France, Florence Fouque, TDR, WHO, Lyon, France, Stephen Francesconi, Defence Threat Reduction Agency, Washington, DC, USA, Anna Funk, Emerging Diseases Epidemiology Unit, Institut Pasteur, Paris, France, Finnian Hanrahan, DG Research, European Commission, Brussels, Belgium, Mireille Harimalala, Medical Entomology Unit, Institut Pasteur de Madagascar, Antananarivo, Madagascar, Nadia Khellef, Institut Pasteur, Paris, France, Anne-Sophie Le Guern, Yersinia Unit, Institut Pasteur, Paris, France, Nadine Lemaitre, Bacteriology Department, CHU Lille, France, Jean-Claude Manuguerra, CIBU, Institut Pasteur, Paris, France, Jodie Mac Vernon, GLoPID-R, University of Melbourne, Australia, Serge Morand, CIRAD, Bangkok, Thailand, Birgit Nikolay, Infectious Diseases Mathematical Modelling Unit, Institut Pasteur, Paris, France, Juliette Paireau, Infectious Diseases Mathematical Modelling Unit, Institut Pasteur, Paris, France, Anna Paoletti, Ministry for Higher Education and Research, Paris, France, Feno MJ Rakotoarimanana, Epidemiology and Clinical Research Unit, Institut Pasteur de Madagascar, Antananarivo, Madagascar, Zely Randriamanatany, Ministry of Public Health, Antananarivo, Madagascar, Laurent Raskine, Fondation Mérieux, Stéphanie Simon, CEA de Saclay, France, Cathy Roth, Department for International Development, London, UK, Alex Salam, Epidemic Diseases Research Group Oxford (ERGO), Nuffield Department of Medicine, University of Oxford, Oxford, UK, Florent Sebbane, Institut Pasteur de Lille, France, Christophe Shako, Department of Disease Control, Ministry of Health, Democratic Republic of Congo, Quirine Ten Bosch, Epidemiology and Clinical Research Unit, Institut Pasteur de Madagascar, Antananarivo, Madagascar, Kathleen Victoir, Department of International Affairs, Institut Pasteur, Paris, France., Demeure, Christian E., Institut Pasteur [Paris], University of Oxford [Oxford], Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), and Centre National de la Recherche Scientifique (CNRS)-IRD-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de La Réunion (UR)
Subjects: Epidemiology, RC955-962, MESH: Rodentia, Review, Pathology and Laboratory Medicine, Disease Outbreaks, Medical Conditions, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Arctic medicine. Tropical medicine, Case fatality rate, Public and Occupational Health, MESH: Animals, media_common, Mammals, Eukaryota, Neglected Diseases, Bacterial Pathogens, 3. Good health, One Health, Geography, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Medical Microbiology, Public aspects of medicine, S1, Yersinia Pestis, media_common.quotation_subject, Immunology, MESH: Yersinia pestis, Rodentia, Microbiology, 03 medical and health sciences, Vaccine Development, Madagascar, Humans, Microbial Pathogens, MESH: Disease Reservoirs, MESH: Humans, Bacteria, Organisms, Public Health, Environmental and Occupational Health, Biology and Life Sciences, Outbreak, medicine.disease, Invertebrates, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Insect Vectors, 030104 developmental biology, Vector (epidemiology), Africa, Preventive Medicine, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, Bacterial Diseases, 0301 basic medicine, Economic growth, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Geographical Locations, MESH: Madagascar, Medicine and Health Sciences, MESH: Disease Outbreaks, biology, Vaccination and Immunization, Yersinia, Insects, Infectious Diseases, Fleas, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, Vertebrates, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Siphonaptera, Psychological resilience, RA1-1270, Pathogens, Pneumonic plague, Arthropoda, Pneumonic Plagues, 030231 tropical medicine, MESH: Insect Vectors, Plague (disease), Rodents, MESH: Plague, [SDV.IMM.VAC] Life Sciences [q-bio]/Immunology/Vaccinology, medicine, Animals, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, Disease Reservoirs, Plague, MESH: Siphonaptera, biology.organism_classification, Plagues, Yersinia pestis, 13. Climate action, People and Places, Amniotes, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Neglected Diseases, Zoology, Entomology
Abstract: Yersinia pestis, the bacterial causative agent of plague, remains an important threat to human health. Plague is a rodent-borne disease that has historically shown an outstanding ability to colonize and persist across different species, habitats, and environments while provoking sporadic cases, outbreaks, and deadly global epidemics among humans. Between September and November 2017, an outbreak of urban pneumonic plague was declared in Madagascar, which refocused the attention of the scientific community on this ancient human scourge. Given recent trends and plague’s resilience to control in the wild, its high fatality rate in humans without early treatment, and its capacity to disrupt social and healthcare systems, human plague should be considered as a neglected threat. A workshop was held in Paris in July 2018 to review current knowledge about plague and to identify the scientific research priorities to eradicate plague as a human threat. It was concluded that an urgent commitment is needed to develop and fund a strong research agenda aiming to fill the current knowledge gaps structured around 4 main axes: (i) an improved understanding of the ecological interactions among the reservoir, vector, pathogen, and environment; (ii) human and societal responses; (iii) improved diagnostic tools and case management; and (iv) vaccine development. These axes should be cross-cutting, translational, and focused on delivering context-specific strategies. Results of this research should feed a global control and prevention strategy within a “One Health” approach., Author summary The historical aspect of plague makes for fascinating reading, due to its capacity to disrupt human society and its socioeconomic and cultural impacts throughout human history. We argue that the Madagascar outbreak in 2017 is a tipping point in human plague epidemiology and a call to elevate research priorities on plague as a matter of some urgency. In contrast with what occurred with the Ebola virus disease crisis in West Africa between 2013 and 2015 and the new coronaviruses (the emergence of severe acute respiratory syndrome coronavirus [SARS-CoV] and Middle East respiratory syndrome coronavirus [MERS-CoV] as early warnings of the current severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] pandemic), we have an opportunity to act preventively and enable evidence-based measures to avoid major health crises due to plague outbreaks in the near future.
Published: 2020

32. Contributions of mean and shape of blood pressure distribution to worldwide trends and variations in raised blood pressure: A pooled analysis of 1018 population-based measurement studies with 88.6 million participants

Author: Yiallouros, Panayiotis K., Escobedo-de la Peña, Jorge, Zhou, Bin, Bentham, James, Di Cesare, Mariachiara, Bixby, Honor, Danaei, Goodarz, Hajifathalian, Kaveh, Taddei, Cristina, Carrillo-Larco, Rodrigo M., Djalalinia, Shirin, Khatibzadeh, Shahab, Lugero, Charles, Peykari, Niloofar, Zhang, Wan Zhu, Bennett, James, Bilano, Ver, Stevens, Gretchen A., Cowan, Melanie J., Riley, Leanne M., Chen, Zhengming, Hambleton, Ian R., Jackson, Rod T., Kengne, Andre Pascal, Khang, Young-Ho, Laxmaiah, Avula, Liu, Jing, Malekzadeh, Reza, Neuhauser, Hannelore K., Sorić, Maroje, Starc, Gregor, Sundström, Johan, Woodward, Mark, Ezzati, Majid, Abarca-Gómez, Leandra, Abdeen, Ziad A., Abu-Rmeileh, Niveen M., Acosta-Cazares, Benjamin, Adams, Robert J., Aekplakorn, Wichai, Afsana, Kaosar, Aguilar-Salinas, Carlos A., Agyemang, Charles, Ahmad, Noor Ani, Ahmadvand, Alireza, Ahrens, Wolfgang, Ajlouni, Kamel, Akhtaeva, Nazgul, Al-Raddadi, Rajaa, Ali, Mohamed M., Ali, Osman, Alkerwi, Ala'a, Aly, Eman, Amarapurkar, Deepak N., Amouyel, Philippe, Amuzu, Antoinette, Andersen, Lars Bo, Anderssen, Sigmund A., Ängquist, Lars H., Anjana, Ranjit Mohan, Ansong, Daniel, Aounallah-Skhiri, Hajer, Araújo, Joana, Ariansen, Inger, Aris, Tahir, Arlappa, Nimmathota, Arveiler, Dominique, Aryal, Krishna K., Aspelund, Thor, Assah, Felix K., Assunção, Maria Cecília F., Avdicová, Mária, Azevedo, Ana, Azizi, Fereidoun, Babu, Bontha V., Bahijri, Suhad, Balakrishna, Nagalla, Bamoshmoosh, Mohamed, Banach, Maciej, Bandosz, Piotr, Banegas, José R., Barbagallo, Carlo M., Barceló, Alberto, Barkat, Amina, Barros, Aluisio J. D., Barros, Mauro V., Bata, Iqbal, Batieha, Anwar M., Batyrbek, Assembekov, Baur, Louise A., Beaglehole, Robert, Romdhane, Habiba Ben, Benet, Mikhail, Benson, Lowell S., Bernabe-Ortiz, Antonio, Bernotiene, Gailute, Bettiol, Heloisa, Bhagyalaxmi, Aroor, Bharadwaj, Sumit, Bhargava, Santosh K., Bi, Yufang, Bikbov, Mukharram, Bista, Bihungum, Bjerregaard, Peter, Bjertness, Espen, Bjertness, Marius B., Björkelund, Cecilia, Blokstra, Anneke, Bo, Simona, Bobak, Martin, Boeing, Heiner, Boggia, Jose G., Boissonnet, Carlos P., Bongard, Vanina, Borchini, Rossana, Bovet, Pascal, Braeckman, Lutgart, Brajkovich, Imperia, Branca, Francesco, Breckenkamp, Juergen, Brenner, Hermann, Brewster, Lizzy M., Bruno, Graziella, Bueno-de-Mesquita, H. B(as), Bugge, Anna, Burns, Con, Bursztyn, Michael, de León, Antonio Cabrera, Cacciottolo, Joseph, Cai, Hui, Cameron, Christine, Can, Günay, Cândido, Ana Paula C., Capuano, Vincenzo, Cardoso, Viviane C., Carlsson, Axel C., Carvalho, Maria J., Casanueva, Felipe F., Casas, Juan-Pablo, Caserta, Carmelo A., Chamukuttan, Snehalatha, Chan, Angelique W., Chan, Queenie, Chaturvedi, Himanshu K., Chaturvedi, Nishi, Chen, Chien-Jen, Chen, Fangfang, Chen, Huashuai, Chen, Shuohua, Cheng, Ching-Yu, Dekkaki, Imane Cherkaoui, Chetrit, Angela, Chiolero, Arnaud, Chiou, Shu-Ti, Chirita-Emandi, Adela, Chirlaque, María-Dolores, Cho, Belong, Cho, Yumi, Christofaro, Diego G., Chudek, Jerzy, Cifkova, Renata, Cinteza, Eliza, Claessens, Frank, Clays, Els, Concin, Hans, Cooper, Cyrus, Cooper, Rachel, Coppinger, Tara C., Costanzo, Simona, Cottel, Dominique, Cowell, Chris, Craig, Cora L., Crujeiras, Ana B., Cruz, Juan J., D'Arrigo, Graziella, d'Orsi, Eleonora, Dallongeville, Jean, Damasceno, Albertino, Dankner, Rachel, Dantoft, Thomas M., Dauchet, Luc, Davletov, Kairat, De Backer, Guy, De Bacquer, Dirk, de Gaetano, Giovanni, De Henauw, Stefaan, de Oliveira, Paula Duarte, De Smedt, Delphine, Deepa, Mohan, Dehghan, Abbas, Delisle, Hélène, Deschamps, Valérie, Dhana, Klodian, Di Castelnuovo, Augusto F., Dias-da-Costa, Juvenal Soares, Diaz, Alejandro, Dickerson, Ty T., Do, Ha T. P., Donfrancesco, Chiara, Donoso, Silvana P., Döring, Angela, Dorobantu, Maria, Doua, Kouamelan, Drygas, Wojciech, Dulskiene, Virginija, Džakula, Aleksandar, Dzerve, Vilnis, Dziankowska-Zaborszczyk, Elzbieta, Eggertsen, Robert, Ekelund, Ulf, El Ati, Jalila, Elliott, Paul, Elosua, Roberto, Erasmus, Rajiv T., Erem, Cihangir, Eriksen, Louise, Eriksson, Johan G., Evans, Alun, Faeh, David, Fall, Caroline H., Farzadfar, Farshad, Felix-Redondo, Francisco J., Ferguson, Trevor S., Fernandes, Romulo A., Fernández-Bergés, Daniel, Ferrante, Daniel, Ferrari, Marika, Ferreccio, Catterina, Ferrieres, Jean, Finn, Joseph D., Fischer, Krista, Föger, Bernhard, Foo, Leng Huat, Forslund, Ann-Sofie, Forsner, Maria, Fouad, Heba M., Francis, Damian K., do Carmo Franco, Maria, Franco, Oscar H., Frontera, Guillermo, Fuchs, Flavio D., Fuchs, Sandra C., Fujita, Yuki, Furusawa, Takuro, Gaciong, Zbigniew, Galvano, Fabio, Garcia-de-la-Hera, Manoli, Gareta, Dickman, Garnett, Sarah P., Gaspoz, Jean-Michel, Gasull, Magda, Gates, Louise, Geleijnse, Johanna M., Ghasemian, Anoosheh, Ghimire, Anup, Giampaoli, Simona, Gianfagna, Francesco, Gill, Tiffany K., Giovannelli, Jonathan, Goldsmith, Rebecca A., Gonçalves, Helen, Gonzalez-Gross, Marcela, González-Rivas, Juan P., Gorbea, Mariano Bonet, Gottrand, Frederic, Graff-Iversen, Sidsel, Grafnetter, Dušan, Grajda, Aneta, Grammatikopoulou, Maria G., Gregor, Ronald D., Grodzicki, Tomasz, Grøntved, Anders, Grosso, Giuseppe, Gruden, Gabriella, Grujic, Vera, Gu, Dongfeng, Guan, Ong Peng, Gudmundsson, Elias F., Gudnason, Vilmundur, Guerrero, Ramiro, Guessous, Idris, Guimaraes, Andre L., Gulliford, Martin C., Gunnlaugsdottir, Johanna, Gunter, Marc, Gupta, Prakash C., Gupta, Rajeev, Gureje, Oye, Gurzkowska, Beata, Gutierrez, Laura, Gutzwiller, Felix, Hadaegh, Farzad, Halkjær, Jytte, Hardy, Rebecca, Hari Kumar, Rachakulla, Hata, Jun, Hayes, Alison J., He, Jiang, He, Yuna, Elisabeth, Marleen, Henriques, Ana, Cadena, Leticia Hernandez, Herrala, Sauli, Heshmat, Ramin, Hihtaniemi, Ilpo Tapani, Ho, Sai Yin, Ho, Suzanne C., Hobbs, Michael, Hofman, Albert, Dinc, Gonul Horasan, Horimoto, Andrea R. V. R., Hormiga, Claudia M., Horta, Bernardo L., Houti, Leila, Howitt, Christina, Htay, Thein Thein, Htet, Aung Soe, Than Htike, Maung Maung, Hu, Yonghua, Huerta, José María, Huisman, Martijn, Husseini, Abdullatif S., Huybrechts, Inge, Hwalla, Nahla, Iacoviello, Licia, Iannone, Anna G., Ibrahim, Mohsen M., Wong, Norazizah Ibrahim, Ikeda, Nayu, Ikram, M. Arfan, Irazola, Vilma E., Islam, Muhammad, al-Safi Ismail, Aziz, Ivkovic, Vanja, Iwasaki, Masanori, Jacobs, Jeremy M., Jaddou, Hashem, Jafar, Tazeen, Jamrozik, Konrad, Janszky, Imre, Jasienska, Grazyna, Jelaković, Ana, Jelaković, Bojan, Jennings, Garry, Jeong, Seung-lyeal, Jiang, Chao Qiang, Joffres, Michel, Johansson, Mattias, Jokelainen, Jari J., Jonas, Jost B., Jørgensen, Torben, Joshi, Pradeep, Jóźwiak, Jacek, Juolevi, Anne, Jurak, Gregor, Jureša, Vesna, Kaaks, Rudolf, Kafatos, Anthony, Kajantie, Eero O., Kalter-Leibovici, Ofra, Kamaruddin, Nor Azmi, Karki, Khem B., Kasaeian, Amir, Katz, Joanne, Kauhanen, Jussi, Kaur, Prabhdeep, Kavousi, Maryam, Kazakbaeva, Gyulli, Keil, Ulrich, Boker, Lital Keinan, Keinänen-Kiukaanniemi, Sirkka, Kelishadi, Roya, Kemper, Han C. G., Kengne, Andre P., Kerimkulova, Alina, Kersting, Mathilde, Key, Timothy, Khader, Yousef Saleh, Khalili, Davood, Khateeb, Mohammad, Khaw, Kay-Tee, Kiechl-Kohlendorfer, Ursula, Kiechl, Stefan, Killewo, Japhet, Kim, Jeongseon, Kim, Yeon-Yong, Klumbiene, Jurate, Knoflach, Michael, Kolle, Elin, Kolsteren, Patrick, Korrovits, Paul, Koskinen, Seppo, Kouda, Katsuyasu, Kowlessur, Sudhir, Koziel, Slawomir, Kriemler, Susi, Kristensen, Peter Lund, Krokstad, Steinar, Kromhout, Daan, Kruger, Herculina S., Kubinova, Ruzena, Kuciene, Renata, Kuh, Diana, Kujala, Urho M., Kulaga, Zbigniew, Krishna Kumar, R., Kurjata, Pawel, Kusuma, Yadlapalli S., Kuulasmaa, Kari, Kyobutungi, Catherine, Laatikainen, Tiina, Lachat, Carl, Lam, Tai Hing, Landrove, Orlando, Lanska, Vera, Lappas, Georg, Larijani, Bagher, Laugsand, Lars E., Le Nguyen Bao, Khanh, Le, Tuyen D., Leclercq, Catherine, Lee, Jeannette, Lee, Jeonghee, Lehtimäki, Terho, León-Muñoz, Luz M., Levitt, Naomi S., Li, Yanping, Lilly, Christa L., Lim, Wei-Yen, Lima-Costa, M. Fernanda, Lin, Hsien-Ho, Lin, Xu, Lind, Lars, Linneberg, Allan, Lissner, Lauren, Litwin, Mieczyslaw, Lorbeer, Roberto, Lotufo, Paulo A., Lozano, José Eugenio, Luksiene, Dalia, Lundqvist, Annamari, Lunet, Nuno, Lytsy, Per, Ma, Guansheng, Ma, Jun, Machado-Coelho, George L. L., Machi, Suka, Maggi, Stefania, Magliano, Dianna J., Magriplis, Emmanuella, Majer, Marjeta, Makdisse, Marcia, Malhotra, Rahul, Mallikharjuna Rao, Kodavanti, Malyutina, Sofia, Manios, Yannis, Mann, Jim I., Manzato, Enzo, Margozzini, Paula, Marques-Vidal, Pedro, Marques, Larissa Pruner, Marrugat, Jaume, Martorell, Reynaldo, Mathiesen, Ellisiv B., Matijasevich, Alicia, Matsha, Tandi E., Mbanya, Jean Claude N., Mc Donald Posso, Anselmo J., McFarlane, Shelly R., McGarvey, Stephen T., McLachlan, Stela, McLean, Rachael M., McLean, Scott B., McNulty, Breige A., Mediene-Benchekor, Sounnia, Medzioniene, Jurate, Meirhaeghe, Aline, Meisinger, Christa, Menezes, Ana Maria B., Menon, Geetha R., Meshram, Indrapal I., Metspalu, Andres, Meyer, Haakon E., Mi, Jie, Mikkel, Kairit, Miller, Jody C., Minderico, Cláudia S., Francisco, Juan, Miranda, J. Jaime, Mirrakhimov, Erkin, Mišigoj-Durakovic, Marjeta, Modesti, Pietro A., Mohamed, Mostafa K., Mohammad, Kazem, Mohammadifard, Noushin, Mohan, Viswanathan, Mohanna, Salim, Mohd Yusoff, Muhammad Fadhli, Møllehave, Line T., Møller, Niels C., Molnár, Dénes, Momenan, Amirabbas, Mondo, Charles K., Monyeki, Kotsedi Daniel K., Moon, Jin Soo, Moreira, Leila B., Morejon, Alain, Moreno, Luis A., Morgan, Karen, Moschonis, George, Mossakowska, Malgorzata, Mostafa, Aya, Mota, Jorge, Esmaeel Motlagh, Mohammad, Motta, Jorge, Msyamboza, Kelias P., Mu, Thet Thet, Muiesan, Maria L., Müller-Nurasyid, Martina, Murphy, Neil, Mursu, Jaakko, Musil, Vera, Nabipour, Iraj, Nagel, Gabriele, Naidu, Balkish M., Nakamura, Harunobu, Námešná, Jana, Nang, Ei Ei K., Nangia, Vinay B., Narake, Sameer, Nauck, Matthias, Navarrete-Muñoz, Eva Maria, Ndiaye, Ndeye Coumba, Neal, William A., Nenko, Ilona, Neovius, Martin, Nervi, Flavio, Nguyen, Chung T., Nguyen, Nguyen D., Nguyen, Quang Ngoc, Nguyen, Quang V., Nieto-Martínez, Ramfis E., Niiranen, Teemu J., Ning, Guang, Ninomiya, Toshiharu, Nishtar, Sania, Noale, Marianna, Noboa, Oscar A., Noorbala, Ahmad Ali, Norat, Teresa, Noto, Davide, Al Nsour, Mohannad, O'Reilly, Dermot, Oda, Eiji, Oehlers, Glenn, Oh, Kyungwon, Ohara, Kumiko, Olinto, Maria Teresa A., Oliveira, Isabel O., Omar, Mohd Azahadi, Onat, Altan, Ong, Sok King, Ono, Lariane M., Ordunez, Pedro, Ornelas, Rui, Osmond, Clive, Ostojic, Sergej M., Ostovar, Afshin, Otero, Johanna A., Overvad, Kim, Owusu-Dabo, Ellis, Paccaud, Fred Michel, Padez, Cristina, Pahomova, Elena, Pajak, Andrzej, Palli, Domenico, Palmieri, Luigi, Pan, Wen-Harn, Panda-Jonas, Songhomitra, Panza, Francesco, Papandreou, Dimitrios, Park, Soon-Woo, Parnell, Winsome R., Parsaeian, Mahboubeh, Patel, Nikhil D., Pecin, Ivan, Pednekar, Mangesh S., Peer, Nasheeta, Peeters, Petra H., Peixoto, Sergio Viana, Peltonen, Markku, Pereira, Alexandre C., Peters, Annette, Petersmann, Astrid, Petkeviciene, Janina, Pham, Son Thai, Pigeot, Iris, Pikhart, Hynek, Pilav, Aida, Pilotto, Lorenza, Pitakaka, Freda, Piwonska, Aleksandra, Plans-Rubió, Pedro, Polašek, Ozren, Porta, Miquel, Portegies, Marileen L. P., Pourshams, Akram, Poustchi, Hossein, Pradeepa, Rajendra, Prashant, Mathur, Price, Jacqueline F., Puder, Jardena J., Puiu, Maria, Punab, Margus, Qasrawi, Radwan F., Qorbani, Mostafa, Bao, Tran Quoc, Radic, Ivana, Radisauskas, Ricardas, Rahman, Mahfuzar, Raitakari, Olli, Raj, Manu, Ramachandra Rao, Sudha, Ramachandran, Ambady, Ramos, Elisabete, Rampal, Lekhraj, Rampal, Sanjay, Rangel Reina, Daniel A., Redon, Josep, Reganit, Paul Ferdinand M., Ribeiro, Robespierre, Riboli, Elio, Rigo, Fernando, Rinke de Wit, Tobias F., Ritti-Dias, Raphael M., Robinson, Sian M., Robitaille, Cynthia, Rodríguez-Artalejo, Fernando, del Cristo Rodriguez-Perez, María, Rodríguez-Villamizar, Laura A., Rojas-Martinez, Rosalba, Romaguera, Dora, Ronkainen, Kimmo, Rosengren, Annika, Roy, Joel G. R., Rubinstein, Adolfo, Sandra Ruiz-Betancourt, Blanca, Rutkowski, Marcin, Sabanayagam, Charumathi, Sachdev, Harshpal S., Saidi, Olfa, Sakarya, Sibel, Salanave, Benoit, Salazar Martinez, Eduardo, Salmerón, Diego, Salomaa, Veikko, Salonen, Jukka T., Salvetti, Massimo, Sánchez-Abanto, Jose, Sans, Susana, Santos, Diana A., Santos, Ina S., Nunes dos Santos, Renata, Santos, Rute, Saramies, Jouko L., Sardinha, Luis B., Sarganas, Giselle, Sarrafzadegan, Nizal, Saum, Kai-Uwe, Savva, Savvas, Scazufca, Marcia, Schargrodsky, Herman, Schipf, Sabine, Schmidt, Carsten O., Schöttker, Ben, Schultsz, Constance, Schutte, Aletta E., Sein, Aye Aye, Sen, Abhijit, Senbanjo, Idowu O., Sepanlou, Sadaf G., Sharma, Sanjib K., Shaw, Jonathan E., Shibuya, Kenji, Shin, Dong Wook, Shin, Youchan, Si-Ramlee, Khairil, Siantar, Rosalynn, Sibai, Abla M., Santos Silva, Diego Augusto, Simon, Mary, Simons, Judith, Simons, Leon A., Sjöström, Michael, Skovbjerg, Sine, Slowikowska-Hilczer, Jolanta, Slusarczyk, Przemyslaw, Smeeth, Liam, Smith, Margaret C., Snijder, Marieke B., So, Hung-Kwan, Sobngwi, Eugène, Söderberg, Stefan, Solfrizzi, Vincenzo, Sonestedt, Emily, Song, Yi, Sørensen, Thorkild I. A., Soric, Maroje, Jérome, Charles Sossa, Soumare, Aicha, Staessen, Jan A., Stathopoulou, Maria G., Stavreski, Bill, Steene-Johannessen, Jostein, Stehle, Peter, Stein, Aryeh D., Stergiou, George S., Stessman, Jochanan, Stieber, Jutta, Stöckl, Doris, Stocks, Tanja, Stokwiszewski, Jakub, Stronks, Karien, Strufaldi, Maria Wany, Sun, Chien-An, Sung, Yn-Tz, Suriyawongpaisal, Paibul, Sy, Rody G., Shyong Tai, E., Tammesoo, Mari-Liis, Tamosiunas, Abdonas, Tan, Eng Joo, Tang, Xun, Tanser, Frank, Tao, Yong, Tarawneh, Mohammed Rasoul, Tarqui-Mamani, Carolina B., Tautu, Oana-Florentina, Taylor, Anne, Theobald, Holger, Theodoridis, Xenophon, Thijs, Lutgarde, Thuesen, Betina H., Tjonneland, Anne, Tolonen, Hanna K., Tolstrup, Janne S., Topbas, Murat, Topór-Madry, Roman, Tormo, María José, Torrent, Maties, Traissac, Pierre, Trichopoulos, Dimitrios, Trichopoulou, Antonia, Trinh, Oanh T. H., Trivedi, Atul, Tshepo, Lechaba, Tulloch-Reid, Marshall K., Tullu, Fikru, Tuomainen, Tomi-Pekka, Tuomilehto, Jaakko, Turley, Maria L., Tynelius, Per, Tzourio, Christophe, Ueda, Peter, Ugel, Eunice E., Ulmer, Hanno, Uusitalo, Hannu M. T., Valdivia, Gonzalo, Valvi, Damaskini, van der Schouw, Yvonne T., Van Herck, Koen, Van Minh, Hoang, van Rossem, Lenie, Van Schoor, Natasja M., van Valkengoed, Irene G. M., Vanderschueren, Dirk, Vanuzzo, Diego, Vatten, Lars, Vega, Tomas, Velasquez-Melendez, Gustavo, Veronesi, Giovanni, Monique Verschuren, W. M., Verstraeten, Roosmarijn, Victora, Cesar G., Viet, Lucie, Viikari-Juntura, Eira, Vineis, Paolo, Vioque, Jesus, Virtanen, Jyrki K., Visvikis-Siest, Sophie, Viswanathan, Bharathi, Vlasoff, Tiina, Vollenweider, Peter, Voutilainen, Sari, Wade, Alisha N., Wagner, Aline, Walton, Janette, Wan Bebakar, Wan Mohamad, Wan Mohamud, Wan Nazaimoon, Wanderley, Rildo S., Wang, Ming-Dong, Wang, Qian, Wang, Ya Xing, Wang, Ying-Wei, Wannamethee, S. 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Aguilar-Salinas, C.A., Agyemang, C., Ahmad, N.A., Ahmadvand, A., Ahrens, W., Ajlouni, K., Akhtaeva, N., Al-Raddadi, R., Ali, M.M., Ali, O., Alkerwi, A., Aly, E., Amarapurkar, D.N., Amouyel, P., Amuzu, A., Andersen, L.B., Anderssen, S.A., Ängquist, L.H., Anjana, R.M., Ansong, D., Aounallah-Skhiri, H., Araújo, J., Ariansen, I., Aris, T., Arlappa, N., Arveiler, D., Aryal, K.K., Aspelund, T., Assah, F.K., Assunção, MCF, Avdicová, M., Azevedo, A., Azizi, F., Babu, B.V., Bahijri, S., Balakrishna, N., Bamoshmoosh, M., Banach, M., Bandosz, P., Banegas, J.R., Barbagallo, C.M., Barceló, A., Barkat, A., Barros, AJD, Barros, M.V., Bata, I., Batieha, A.M., Batyrbek, A., Baur, L.A., Beaglehole, R., Romdhane, H.B., Benet, M., Benson, L.S., Bernabe-Ortiz, A., Bernotiene, G., Bettiol, H., Bhagyalaxmi, A., Bharadwaj, S., Bhargava, S.K., Bi, Y., Bikbov, M., Bista, B., Bjerregaard, P., Bjertness, E., Bjertness, M.B., Björkelund, C., Blokstra, A., Bo, S., Bobak, M., Boeing, H., Boggia, J.G., Boissonnet, C.P., Bongard, V., Borchini, R., Bovet, P., Braeckman, L., Brajkovich, I., Branca, F., Breckenkamp, J., Brenner, H., Brewster, L.M., Bruno, G., Bueno-de-Mesquita, HBA, Bugge, A., Burns, C., Bursztyn, M., de León, A.C., Cacciottolo, J., Cai, H., Cameron, C., Can, G., Cândido, APC, Capuano, V., Cardoso, V.C., Carlsson, A.C., Carvalho, M.J., Casanueva, F.F., Casas, J.P., Caserta, C.A., Chamukuttan, S., Chan, A.W., Chan, Q., Chaturvedi, H.K., Chaturvedi, N., Chen, C.J., Chen, F., Chen, H., Chen, S., Cheng, C.Y., Dekkaki, I.C., Chetrit, A., Chiolero, A., Chiou, S.T., Chirita-Emandi, A., Chirlaque, M.D., Cho, B., Cho, Y., Christofaro, D.G., Chudek, J., Cifkova, R., Cinteza, E., Claessens, F., Clays, E., Concin, H., Cooper, C., Cooper, R., Coppinger, T.C., Costanzo, S., Cottel, D., Cowell, C., Craig, C.L., Crujeiras, A.B., Cruz, J.J., D'Arrigo, G., d'Orsi, E., Dallongeville, J., Damasceno, A., Dankner, R., Dantoft, T.M., Dauchet, L., Davletov, K., De Backer, G., De Bacquer, D., de Gaetano, G., De Henauw, S., de Oliveira, P.D., De Smedt, D., Deepa, M., Dehghan, A., Delisle, H., Deschamps, V., Dhana, K., Di Castelnuovo, A.F., Dias-da-Costa, J.S., Diaz, A., Dickerson, T.T., Do, HTP, Donfrancesco, C., Donoso, S.P., Döring, A., Dorobantu, M., Doua, K., Drygas, W., Dulskiene, V., Džakula, A., Dzerve, V., Dziankowska-Zaborszczyk, E., Eggertsen, R., Ekelund, U., El Ati, J., Elliott, P., Elosua, R., Erasmus, R.T., Erem, C., Eriksen, L., Eriksson, J.G., Escobedo-de la Peña, J., Evans, A., Faeh, D., Fall, C.H., Farzadfar, F., Felix-Redondo, F.J., Ferguson, T.S., Fernandes, R.A., Fernández-Bergés, D., Ferrante, D., Ferrari, M., Ferreccio, C., Ferrieres, J., Finn, J.D., Fischer, K., Föger, B., Foo, L.H., Forslund, A.S., Forsner, M., Fouad, H.M., Francis, D.K., do Carmo Franco, M., Franco, O.H., Frontera, G., Fuchs, F.D., Fuchs, S.C., Fujita, Y., Furusawa, T., Gaciong, Z., Galvano, F., Garcia-de-la-Hera, M., Gareta, D., Garnett, S.P., Gaspoz, J.M., Gasull, M., Gates, L., Geleijnse, J.M., Ghasemian, A., Ghimire, A., Giampaoli, S., Gianfagna, F., Gill, T.K., Giovannelli, J., Goldsmith, R.A., Gonçalves, H., Gonzalez-Gross, M., González-Rivas, J.P., Gorbea, M.B., Gottrand, F., Graff-Iversen, S., Grafnetter, D., Grajda, A., Grammatikopoulou, M.G., Gregor, R.D., Grodzicki, T., Grøntved, A., Grosso, G., Gruden, G., Grujic, V., Gu, D., Guan, O.P., Gudmundsson, E.F., Gudnason, V., Guerrero, R., Guessous, I., Guimaraes, A.L., Gulliford, M.C., Gunnlaugsdottir, J., Gunter, M., Gupta, P.C., Gupta, R., Gureje, O., Gurzkowska, B., Gutierrez, L., Gutzwiller, F., Hadaegh, F., Halkjær, J., Hardy, R., Hari Kumar, R., Hata, J., Hayes, A.J., He, J., He, Y., Elisabeth, M., Henriques, A., Cadena, L.H., Herrala, S., Heshmat, R., Hihtaniemi, I.T., Ho, S.Y., Ho, S.C., Hobbs, M., Hofman, A., Dinc, G.H., Horimoto, ARVR, Hormiga, C.M., Horta, B.L., Houti, L., Howitt, C., Htay, T.T., Htet, A.S., Than Htike, M.M., Hu, Y., Huerta, J.M., Huisman, M., Husseini, A.S., Huybrechts, I., Hwalla, N., Iacoviello, L., Iannone, A.G., Ibrahim, M.M., Wong, N.I., Ikeda, N., Ikram, M.A., Irazola, V.E., Islam, M., Al-Safi Ismail, A., Ivkovic, V., Iwasaki, M., Jacobs, J.M., Jaddou, H., Jafar, T., Jamrozik, K., Janszky, I., Jasienska, G., Jelaković, A., Jelaković, B., Jennings, G., Jeong, S.L., Jiang, C.Q., Joffres, M., Johansson, M., Jokelainen, J.J., Jonas, J.B., Jørgensen, T., Joshi, P., Jóźwiak, J., Juolevi, A., Jurak, G., Jureša, V., Kaaks, R., Kafatos, A., Kajantie, E.O., Kalter-Leibovici, O., Kamaruddin, N.A., Karki, K.B., Kasaeian, A., Katz, J., Kauhanen, J., Kaur, P., Kavousi, M., Kazakbaeva, G., Keil, U., Boker, L.K., Keinänen-Kiukaanniemi, S., Kelishadi, R., Kemper, HCG, Kerimkulova, A., Kersting, M., Key, T., Khader, Y.S., Khalili, D., Khateeb, M., Khaw, K.T., Kiechl-Kohlendorfer, U., Kiechl, S., Killewo, J., Kim, J., Kim, Y.Y., Klumbiene, J., Knoflach, M., Kolle, E., Kolsteren, P., Korrovits, P., Koskinen, S., Kouda, K., Kowlessur, S., Koziel, S., Kriemler, S., Kristensen, P.L., Krokstad, S., Kromhout, D., Kruger, H.S., Kubinova, R., Kuciene, R., Kuh, D., Kujala, U.M., Kulaga, Z., Krishna Kumar, R., Kurjata, P., Kusuma, Y.S., Kuulasmaa, K., Kyobutungi, C., Laatikainen, T., Lachat, C., Lam, T.H., Landrove, O., Lanska, V., Lappas, G., Larijani, B., Laugsand, L.E., Le Nguyen Bao, K., Le, T.D., Leclercq, C., Lee, J., Lehtimäki, T., León-Muñoz, L.M., Levitt, N.S., Li, Y., Lilly, C.L., Lim, W.Y., Lima-Costa, M.F., Lin, H.H., Lin, X., Lind, L., Linneberg, A., Lissner, L., Litwin, M., Lorbeer, R., Lotufo, P.A., Lozano, J.E., Luksiene, D., Lundqvist, A., Lunet, N., Lytsy, P., Ma, G., Ma, J., Machado-Coelho, GLL, Machi, S., Maggi, S., Magliano, D.J., Magriplis, E., Majer, M., Makdisse, M., Malhotra, R., Mallikharjuna Rao, K., Malyutina, S., Manios, Y., Mann, J.I., Manzato, E., Margozzini, P., Marques-Vidal, P., Marques, L.P., Marrugat, J., Martorell, R., Mathiesen, E.B., Matijasevich, A., Matsha, T.E., Mbanya, JCN, Mc Donald Posso, A.J., McFarlane, S.R., McGarvey, S.T., McLachlan, S., McLean, R.M., McLean, S.B., McNulty, B.A., Mediene-Benchekor, S., Medzioniene, J., Meirhaeghe, A., Meisinger, C., Menezes, AMB, Menon, G.R., Meshram, I.I., Metspalu, A., Meyer, H.E., Mi, J., Mikkel, K., Miller, J.C., Minderico, C.S., Francisco, J., Miranda, J.J., Mirrakhimov, E., Mišigoj-Durakovic, M., Modesti, P.A., Mohamed, M.K., Mohammad, K., Mohammadifard, N., Mohan, V., Mohanna, S., Mohd Yusoff, M.F., Møllehave, L.T., Møller, N.C., Molnár, D., Momenan, A., Mondo, C.K., Monyeki, KDK, Moon, J.S., Moreira, L.B., Morejon, A., Moreno, L.A., Morgan, K., Moschonis, G., Mossakowska, M., Mostafa, A., Mota, J., Esmaeel Motlagh, M., Motta, J., Msyamboza, K.P., Mu, T.T., Muiesan, M.L., Müller-Nurasyid, M., Murphy, N., Mursu, J., Musil, V., Nabipour, I., Nagel, G., Naidu, B.M., Nakamura, H., Námešná, J., Nang, EEK, Nangia, V.B., Narake, S., Nauck, M., Navarrete-Muñoz, E.M., Ndiaye, N.C., Neal, W.A., Nenko, I., Neovius, M., Nervi, F., Nguyen, C.T., Nguyen, N.D., Nguyen, Q.N., Nguyen, Q.V., Nieto-Martínez, R.E., Niiranen, T.J., Ning, G., Ninomiya, T., Nishtar, S., Noale, M., Noboa, O.A., Noorbala, A.A., Norat, T., Noto, D., Al Nsour, M., O'Reilly, D., Oda, E., Oehlers, G., Oh, K., Ohara, K., Olinto, MTA, Oliveira, I.O., Omar, M.A., Onat, A., Ong, S.K., Ono, L.M., Ordunez, P., Ornelas, R., Osmond, C., Ostojic, S.M., Ostovar, A., Otero, J.A., Overvad, K., Owusu-Dabo, E., Paccaud, F.M., Padez, C., Pahomova, E., Pajak, A., Palli, D., Palmieri, L., Pan, W.H., Panda-Jonas, S., Panza, F., Papandreou, D., Park, S.W., Parnell, W.R., Parsaeian, M., Patel, N.D., Pecin, I., Pednekar, M.S., Peer, N., Peeters, P.H., Peixoto, S.V., Peltonen, M., Pereira, A.C., Peters, A., Petersmann, A., Petkeviciene, J., Pham, S.T., Pigeot, I., Pikhart, H., Pilav, A., Pilotto, L., Pitakaka, F., Piwonska, A., Plans-Rubió, P., Polašek, O., Porta, M., Portegies, MLP, Pourshams, A., Poustchi, H., Pradeepa, R., Prashant, M., Price, J.F., Puder, J.J., Puiu, M., Punab, M., Qasrawi, R.F., Qorbani, M., Bao, T.Q., Radic, I., Radisauskas, R., Rahman, M., Raitakari, O., Raj, M., Ramachandra Rao, S., Ramachandran, A., Ramos, E., Rampal, L., Rampal, S., Rangel Reina, D.A., Redon, J., Reganit, PFM, Ribeiro, R., Riboli, E., Rigo, F., Rinke de Wit, T.F., Ritti-Dias, R.M., Robinson, S.M., Robitaille, C., Rodríguez-Artalejo, F., Del Cristo Rodriguez-Perez, M., Rodríguez-Villamizar, L.A., Rojas-Martinez, R., Romaguera, D., Ronkainen, K., Rosengren, A., Roy, JGR, Rubinstein, A., Sandra Ruiz-Betancourt, B., Rutkowski, M., Sabanayagam, C., Sachdev, H.S., Saidi, O., Sakarya, S., Salanave, B., Salazar Martinez, E., Salmerón, D., Salomaa, V., Salonen, J.T., Salvetti, M., Sánchez-Abanto, J., Sans, S., Santos, D.A., Santos, I.S., Nunes Dos Santos, R., Santos, R., Saramies, J.L., Sardinha, L.B., Sarganas, G., Sarrafzadegan, N., Saum, K.U., Savva, S., Scazufca, M., Schargrodsky, H., Schipf, S., Schmidt, C.O., Schöttker, B., Schultsz, C., Schutte, A.E., Sein, A.A., Sen, A., Senbanjo, I.O., Sepanlou, S.G., Sharma, S.K., Shaw, J.E., Shibuya, K., Shin, D.W., Shin, Y., Si-Ramlee, K., Siantar, R., Sibai, A.M., Santos Silva, D.A., Simon, M., Simons, J., Simons, L.A., Sjöström, M., Skovbjerg, S., Slowikowska-Hilczer, J., Slusarczyk, P., Smeeth, L., Smith, M.C., Snijder, M.B., So, H.K., Sobngwi, E., Söderberg, S., Solfrizzi, V., Sonestedt, E., Song, Y., Sørensen, TIA, Soric, M., Jérome, C.S., Soumare, A., Staessen, J.A., Stathopoulou, M.G., Stavreski, B., Steene-Johannessen, J., Stehle, P., Stein, A.D., Stergiou, G.S., Stessman, J., Stieber, J., Stöckl, D., Stocks, T., Stokwiszewski, J., Stronks, K., Strufaldi, M.W., Sun, C.A., Sung, Y.T., Suriyawongpaisal, P., Sy, R.G., Shyong Tai, E., Tammesoo, M.L., Tamosiunas, A., Tan, E.J., Tang, X., Tanser, F., Tao, Y., Tarawneh, M.R., Tarqui-Mamani, C.B., Tautu, O.F., Taylor, A., Theobald, H., Theodoridis, X., Thijs, L., Thuesen, B.H., Tjonneland, A., Tolonen, H.K., Tolstrup, J.S., Topbas, M., Topór-Madry, R., Tormo, M.J., Torrent, M., Traissac, P., Trichopoulos, D., Trichopoulou, A., Trinh, OTH, Trivedi, A., Tshepo, L., Tulloch-Reid, M.K., Tullu, F., Tuomainen, T.P., Tuomilehto, J., Turley, M.L., Tynelius, P., Tzourio, C., Ueda, P., Ugel, E.E., Ulmer, H., Uusitalo, HMT, Valdivia, G., Valvi, D., van der Schouw, Y.T., Van Herck, K., Van Minh, H., van Rossem, L., Van Schoor, N.M., van Valkengoed, IGM, Vanderschueren, D., Vanuzzo, D., Vatten, L., Vega, T., Velasquez-Melendez, G., Veronesi, G., Monique Verschuren, W.M., Verstraeten, R., Victora, C.G., Viet, L., Viikari-Juntura, E., Vineis, P., Vioque, J., Virtanen, J.K., Visvikis-Siest, S., Viswanathan, B., Vlasoff, T., Vollenweider, P., Voutilainen, S., Wade, A.N., Wagner, A., Walton, J., Wan Bebakar, W.M., Wan Mohamud, W.N., Wanderley, R.S., Wang, M.D., Wang, Q., Wang, Y.X., Wang, Y.W., Wannamethee, S.G., Wareham, N., Wedderkopp, N., Weerasekera, D., Whincup, P.H., Widhalm, K., Widyahening, I.S., Wiecek, A., Wijga, A.H., Wilks, R.J., Willeit, J., Willeit, P., Williams, E.A., Wilsgaard, T., Wojtyniak, B., Wong-McClure, R.A., Wong, JYY, Wong, T.Y., Woo, J., Giwercman Wu, A., Wu, F.C., Wu, S., Xu, H., Yan, W., Yang, X., Ye, X., Yiallouros, P.K., Yoshihara, A., Younger-Coleman, N.O., Yusoff, A.F., Zainuddin, A.A., Zambon, S., Zampelas, A., Zdrojewski, T., Zeng, Y., Zhao, D., Zhao, W., Zheng, W., Zheng, Y., Zhu, D., Zhussupov, B., Zimmermann, E., Cisneros, J.Z., Zhou, Bin, Bentham, Jame, Di Cesare, Mariachiara, Bixby, Honor, Danaei, Goodarz, Hajifathalian, Kaveh, Taddei, Cristina, Carrillo-Larco, Rodrigo M, Djalalinia, Shirin, Khatibzadeh, Shahab, Lugero, Charle, Peykari, Niloofar, Zhang, Wan Zhu, Bennett, Jame, Bilano, Ver, Stevens, Gretchen A, Cowan, Melanie J, Riley, Leanne M, Chen, Zhengming, Hambleton, Ian R, Jackson, Rod T, Kengne, Andre Pascal, Khang, Young-Ho, Laxmaiah, Avula, Liu, Jing, Malekzadeh, Reza, Neuhauser, Hannelore K, Sorić, Maroje, Starc, Gregor, Sundström, Johan, Woodward, Mark, Ezzati, Majid, Abarca-Gómez, Leandra, Abdeen, Ziad A, Abu-Rmeileh, Niveen M, Acosta-Cazares, Benjamin, Adams, Robert J, Aekplakorn, Wichai, Afsana, Kaosar, Aguilar-Salinas, Carlos A, Agyemang, Charle, Ahmad, Noor Ani, Ahmadvand, Alireza, Ahrens, Wolfgang, Ajlouni, Kamel, Akhtaeva, Nazgul, Al-Raddadi, Rajaa, Ali, Mohamed M, Ali, Osman, Alkerwi, Ala'a, Aly, Eman, Amarapurkar, Deepak N, Amouyel, Philippe, Amuzu, Antoinette, Andersen, Lars Bo, Anderssen, Sigmund A, Ängquist, Lars H, Anjana, Ranjit Mohan, Ansong, Daniel, Aounallah-Skhiri, Hajer, Araújo, Joana, Ariansen, Inger, Aris, Tahir, Arlappa, Nimmathota, Arveiler, Dominique, Aryal, Krishna K, Aspelund, Thor, Assah, Felix K, Assunção, Maria Cecília F, Avdicová, Mária, Azevedo, Ana, Azizi, Fereidoun, Babu, Bontha V, Bahijri, Suhad, Balakrishna, Nagalla, Bamoshmoosh, Mohamed, Banach, Maciej, Bandosz, Piotr, Banegas, José R, Barbagallo, Carlo M, Barceló, Alberto, Barkat, Amina, Barros, Aluisio J D, Barros, Mauro V, Bata, Iqbal, Batieha, Anwar M, Batyrbek, Assembekov, Baur, Louise A, Beaglehole, Robert, Romdhane, Habiba Ben, Benet, Mikhail, Benson, Lowell S, Bernabe-Ortiz, Antonio, Bernotiene, Gailute, Bettiol, Heloisa, Bhagyalaxmi, Aroor, Bharadwaj, Sumit, Bhargava, Santosh K, Bi, Yufang, Bikbov, Mukharram, Bista, Bihungum, Bjerregaard, Peter, Bjertness, Espen, Bjertness, Marius B, Björkelund, Cecilia, Blokstra, Anneke, Bo, Simona, Bobak, Martin, Boeing, Heiner, Boggia, Jose G, Boissonnet, Carlos P, Bongard, Vanina, Borchini, Rossana, Bovet, Pascal, Braeckman, Lutgart, Brajkovich, Imperia, Branca, Francesco, Breckenkamp, Juergen, Brenner, Hermann, Brewster, Lizzy M, Bruno, Graziella, Bueno-de-Mesquita, H B(as), Bugge, Anna, Burns, Con, Bursztyn, Michael, de León, Antonio Cabrera, Cacciottolo, Joseph, Cai, Hui, Cameron, Christine, Can, Günay, Cândido, Ana Paula C, Capuano, Vincenzo, Cardoso, Viviane C, Carlsson, Axel C, Carvalho, Maria J, Casanueva, Felipe F, Casas, Juan-Pablo, Caserta, Carmelo A, Chamukuttan, Snehalatha, Chan, Angelique W, Chan, Queenie, Chaturvedi, Himanshu K, Chaturvedi, Nishi, Chen, Chien-Jen, Chen, Fangfang, Chen, Huashuai, Chen, Shuohua, Cheng, Ching-Yu, Dekkaki, Imane Cherkaoui, Chetrit, Angela, Chiolero, Arnaud, Chiou, Shu-Ti, Chirita-Emandi, Adela, Chirlaque, María-Dolore, Cho, Belong, Cho, Yumi, Christofaro, Diego G, Chudek, Jerzy, Cifkova, Renata, Cinteza, Eliza, Claessens, Frank, Clays, El, Concin, Han, Cooper, Cyru, Cooper, Rachel, Coppinger, Tara C, Costanzo, Simona, Cottel, Dominique, Cowell, Chri, Craig, Cora L, Crujeiras, Ana B, Cruz, Juan J, D'Arrigo, Graziella, d'Orsi, Eleonora, Dallongeville, Jean, Damasceno, Albertino, Dankner, Rachel, Dantoft, Thomas M, Dauchet, Luc, Davletov, Kairat, De Backer, Guy, De Bacquer, Dirk, de Gaetano, Giovanni, De Henauw, Stefaan, de Oliveira, Paula Duarte, De Smedt, Delphine, Deepa, Mohan, Dehghan, Abba, Delisle, Hélène, Deschamps, Valérie, Dhana, Klodian, Di Castelnuovo, Augusto F, Dias-da-Costa, Juvenal Soare, Diaz, Alejandro, Dickerson, Ty T, Do, Ha T P, Donfrancesco, Chiara, Donoso, Silvana P, Döring, Angela, Dorobantu, Maria, Doua, Kouamelan, Drygas, Wojciech, Dulskiene, Virginija, Džakula, Aleksandar, Dzerve, Vilni, Dziankowska-Zaborszczyk, Elzbieta, Eggertsen, Robert, Ekelund, Ulf, El Ati, Jalila, Elliott, Paul, Elosua, Roberto, Erasmus, Rajiv T, Erem, Cihangir, Eriksen, Louise, Eriksson, Johan G, Escobedo-de la Peña, Jorge, Evans, Alun, Faeh, David, Fall, Caroline H, Farzadfar, Farshad, Felix-Redondo, Francisco J, Ferguson, Trevor S, Fernandes, Romulo A, Fernández-Bergés, Daniel, Ferrante, Daniel, Ferrari, Marika, Ferreccio, Catterina, Ferrieres, Jean, Finn, Joseph D, Fischer, Krista, Föger, Bernhard, Foo, Leng Huat, Forslund, Ann-Sofie, Forsner, Maria, Fouad, Heba M, Francis, Damian K, do Carmo Franco, Maria, Franco, Oscar H, Frontera, Guillermo, Fuchs, Flavio D, Fuchs, Sandra C, Fujita, Yuki, Furusawa, Takuro, Gaciong, Zbigniew, Galvano, Fabio, Garcia-de-la-Hera, Manoli, Gareta, Dickman, Garnett, Sarah P, Gaspoz, Jean-Michel, Gasull, Magda, Gates, Louise, Geleijnse, Johanna M, Ghasemian, Anoosheh, Ghimire, Anup, Giampaoli, Simona, Gianfagna, Francesco, Gill, Tiffany K, Giovannelli, Jonathan, Goldsmith, Rebecca A, Gonçalves, Helen, Gonzalez-Gross, Marcela, González-Rivas, Juan P, Gorbea, Mariano Bonet, Gottrand, Frederic, Graff-Iversen, Sidsel, Grafnetter, Dušan, Grajda, Aneta, Grammatikopoulou, Maria G, Gregor, Ronald D, Grodzicki, Tomasz, Grøntved, Ander, Grosso, Giuseppe, Gruden, Gabriella, Grujic, Vera, Gu, Dongfeng, Guan, Ong Peng, Gudmundsson, Elias F, Gudnason, Vilmundur, Guerrero, Ramiro, Guessous, Idri, Guimaraes, Andre L, Gulliford, Martin C, Gunnlaugsdottir, Johanna, Gunter, Marc, Gupta, Prakash C, Gupta, Rajeev, Gureje, Oye, Gurzkowska, Beata, Gutierrez, Laura, Gutzwiller, Felix, Hadaegh, Farzad, Halkjær, Jytte, Hardy, Rebecca, Hari Kumar, Rachakulla, Hata, Jun, Hayes, Alison J, He, Jiang, He, Yuna, Elisabeth, Marleen, Henriques, Ana, Cadena, Leticia Hernandez, Herrala, Sauli, Heshmat, Ramin, Hihtaniemi, Ilpo Tapani, Ho, Sai Yin, Ho, Suzanne C, Hobbs, Michael, Hofman, Albert, Dinc, Gonul Horasan, Horimoto, Andrea R V R, Hormiga, Claudia M, Horta, Bernardo L, Houti, Leila, Howitt, Christina, Htay, Thein Thein, Htet, Aung Soe, Than Htike, Maung Maung, Hu, Yonghua, Huerta, José María, Huisman, Martijn, Husseini, Abdullatif S, Huybrechts, Inge, Hwalla, Nahla, Iacoviello, Licia, Iannone, Anna G, Ibrahim, Mohsen M, Wong, Norazizah Ibrahim, Ikeda, Nayu, Ikram, M Arfan, Irazola, Vilma E, Islam, Muhammad, al-Safi Ismail, Aziz, Ivkovic, Vanja, Iwasaki, Masanori, Jacobs, Jeremy M, Jaddou, Hashem, Jafar, Tazeen, Jamrozik, Konrad, Janszky, Imre, Jasienska, Grazyna, Jelaković, Ana, Jelaković, Bojan, Jennings, Garry, Jeong, Seung-lyeal, Jiang, Chao Qiang, Joffres, Michel, Johansson, Mattia, Jokelainen, Jari J, Jonas, Jost B, Jørgensen, Torben, Joshi, Pradeep, Jóźwiak, Jacek, Juolevi, Anne, Jurak, Gregor, Jureša, Vesna, Kaaks, Rudolf, Kafatos, Anthony, Kajantie, Eero O, Kalter-Leibovici, Ofra, Kamaruddin, Nor Azmi, Karki, Khem B, Kasaeian, Amir, Katz, Joanne, Kauhanen, Jussi, Kaur, Prabhdeep, Kavousi, Maryam, Kazakbaeva, Gyulli, Keil, Ulrich, Boker, Lital Keinan, Keinänen-Kiukaanniemi, Sirkka, Kelishadi, Roya, Kemper, Han C G, Kengne, Andre P, Kerimkulova, Alina, Kersting, Mathilde, Key, Timothy, Khader, Yousef Saleh, Khalili, Davood, Khateeb, Mohammad, Khaw, Kay-Tee, Kiechl-Kohlendorfer, Ursula, Kiechl, Stefan, Killewo, Japhet, Kim, Jeongseon, Kim, Yeon-Yong, Klumbiene, Jurate, Knoflach, Michael, Kolle, Elin, Kolsteren, Patrick, Korrovits, Paul, Koskinen, Seppo, Kouda, Katsuyasu, Kowlessur, Sudhir, Koziel, Slawomir, Kriemler, Susi, Kristensen, Peter Lund, Krokstad, Steinar, Kromhout, Daan, Kruger, Herculina S, Kubinova, Ruzena, Kuciene, Renata, Kuh, Diana, Kujala, Urho M, Kulaga, Zbigniew, Krishna Kumar, R, Kurjata, Pawel, Kusuma, Yadlapalli S, Kuulasmaa, Kari, Kyobutungi, Catherine, Laatikainen, Tiina, Lachat, Carl, Lam, Tai Hing, Landrove, Orlando, Lanska, Vera, Lappas, Georg, Larijani, Bagher, Laugsand, Lars E, Le Nguyen Bao, Khanh, Le, Tuyen D, Leclercq, Catherine, Lee, Jeannette, Lee, Jeonghee, Lehtimäki, Terho, León-Muñoz, Luz M, Levitt, Naomi S, Li, Yanping, Lilly, Christa L, Lim, Wei-Yen, Lima-Costa, M Fernanda, Lin, Hsien-Ho, Lin, Xu, Lind, Lar, Linneberg, Allan, Lissner, Lauren, Litwin, Mieczyslaw, Lorbeer, Roberto, Lotufo, Paulo A, Lozano, José Eugenio, Luksiene, Dalia, Lundqvist, Annamari, Lunet, Nuno, Lytsy, Per, Ma, Guansheng, Ma, Jun, Machado-Coelho, George L L, Machi, Suka, Maggi, Stefania, Magliano, Dianna J, Magriplis, Emmanuella, Majer, Marjeta, Makdisse, Marcia, Malhotra, Rahul, Mallikharjuna Rao, Kodavanti, Malyutina, Sofia, Manios, Yanni, Mann, Jim I, Manzato, Enzo, Margozzini, Paula, Marques-Vidal, Pedro, Marques, Larissa Pruner, Marrugat, Jaume, Martorell, Reynaldo, Mathiesen, Ellisiv B, Matijasevich, Alicia, Matsha, Tandi E, Mbanya, Jean Claude N, Mc Donald Posso, Anselmo J, McFarlane, Shelly R, McGarvey, Stephen T, McLachlan, Stela, McLean, Rachael M, McLean, Scott B, McNulty, Breige A, Mediene-Benchekor, Sounnia, Medzioniene, Jurate, Meirhaeghe, Aline, Meisinger, Christa, Menezes, Ana Maria B, Menon, Geetha R, Meshram, Indrapal I, Metspalu, Andre, Meyer, Haakon E, Mi, Jie, Mikkel, Kairit, Miller, Jody C, Minderico, Cláudia S, Francisco, Juan, Miranda, J Jaime, Mirrakhimov, Erkin, Mišigoj-Durakovic, Marjeta, Modesti, Pietro A, Mohamed, Mostafa K, Mohammad, Kazem, Mohammadifard, Noushin, Mohan, Viswanathan, Mohanna, Salim, Mohd Yusoff, Muhammad Fadhli, Møllehave, Line T, Møller, Niels C, Molnár, Déne, Momenan, Amirabba, Mondo, Charles K, Monyeki, Kotsedi Daniel K, Moon, Jin Soo, Moreira, Leila B, Morejon, Alain, Moreno, Luis A, Morgan, Karen, Moschonis, George, Mossakowska, Malgorzata, Mostafa, Aya, Mota, Jorge, Esmaeel Motlagh, Mohammad, Motta, Jorge, Msyamboza, Kelias P, Mu, Thet Thet, Muiesan, Maria L, Müller-Nurasyid, Martina, Murphy, Neil, Mursu, Jaakko, Musil, Vera, Nabipour, Iraj, Nagel, Gabriele, Naidu, Balkish M, Nakamura, Harunobu, Námešná, Jana, Nang, Ei Ei K, Nangia, Vinay B, Narake, Sameer, Nauck, Matthia, Navarrete-Muñoz, Eva Maria, Ndiaye, Ndeye Coumba, Neal, William A, Nenko, Ilona, Neovius, Martin, Nervi, Flavio, Nguyen, Chung T, Nguyen, Nguyen D, Nguyen, Quang Ngoc, Nguyen, Quang V, Nieto-Martínez, Ramfis E, Niiranen, Teemu J, Ning, Guang, Ninomiya, Toshiharu, Nishtar, Sania, Noale, Marianna, Noboa, Oscar A, Noorbala, Ahmad Ali, Norat, Teresa, Noto, Davide, Al Nsour, Mohannad, O'Reilly, Dermot, Oda, Eiji, Oehlers, Glenn, Oh, Kyungwon, Ohara, Kumiko, Olinto, Maria Teresa A, Oliveira, Isabel O, Omar, Mohd Azahadi, Onat, Altan, Ong, Sok King, Ono, Lariane M, Ordunez, Pedro, Ornelas, Rui, Osmond, Clive, Ostojic, Sergej M, Ostovar, Afshin, Otero, Johanna A, Overvad, Kim, Owusu-Dabo, Elli, Paccaud, Fred Michel, Padez, Cristina, Pahomova, Elena, Pajak, Andrzej, Palli, Domenico, Palmieri, Luigi, Pan, Wen-Harn, Panda-Jonas, Songhomitra, Panza, Francesco, Papandreou, Dimitrio, Park, Soon-Woo, Parnell, Winsome R, Parsaeian, Mahboubeh, Patel, Nikhil D, Pecin, Ivan, Pednekar, Mangesh S, Peer, Nasheeta, Peeters, Petra H, Peixoto, Sergio Viana, Peltonen, Markku, Pereira, Alexandre C, Peters, Annette, Petersmann, Astrid, Petkeviciene, Janina, Pham, Son Thai, Pigeot, Iri, Pikhart, Hynek, Pilav, Aida, Pilotto, Lorenza, Pitakaka, Freda, Piwonska, Aleksandra, Plans-Rubió, Pedro, Polašek, Ozren, Porta, Miquel, Portegies, Marileen L P, Pourshams, Akram, Poustchi, Hossein, Pradeepa, Rajendra, Prashant, Mathur, Price, Jacqueline F, Puder, Jardena J, Puiu, Maria, Punab, Margu, Qasrawi, Radwan F, Qorbani, Mostafa, Bao, Tran Quoc, Radic, Ivana, Radisauskas, Ricarda, Rahman, Mahfuzar, Raitakari, Olli, Raj, Manu, Ramachandra Rao, Sudha, Ramachandran, Ambady, Ramos, Elisabete, Rampal, Lekhraj, Rampal, Sanjay, Rangel Reina, Daniel A, Redon, Josep, Reganit, Paul Ferdinand M, Ribeiro, Robespierre, Riboli, Elio, Rigo, Fernando, Rinke de Wit, Tobias F, Ritti-Dias, Raphael M, Robinson, Sian M, Robitaille, Cynthia, Rodríguez-Artalejo, Fernando, del Cristo Rodriguez-Perez, María, Rodríguez-Villamizar, Laura A, Rojas-Martinez, Rosalba, Romaguera, Dora, Ronkainen, Kimmo, Rosengren, Annika, Roy, Joel G R, Rubinstein, Adolfo, Sandra Ruiz-Betancourt, Blanca, Rutkowski, Marcin, Sabanayagam, Charumathi, Sachdev, Harshpal S, Saidi, Olfa, Sakarya, Sibel, Salanave, Benoit, Salazar Martinez, Eduardo, Salmerón, Diego, Salomaa, Veikko, Salonen, Jukka T, Salvetti, Massimo, Sánchez-Abanto, Jose, Sans, Susana, Santos, Diana A, Santos, Ina S, Nunes dos Santos, Renata, Santos, Rute, Saramies, Jouko L, Sardinha, Luis B, Sarganas, Giselle, Sarrafzadegan, Nizal, Saum, Kai-Uwe, Savva, Savva, Scazufca, Marcia, Schargrodsky, Herman, Schipf, Sabine, Schmidt, Carsten O, Schöttker, Ben, Schultsz, Constance, Schutte, Aletta E, Sein, Aye Aye, Sen, Abhijit, Senbanjo, Idowu O, Sepanlou, Sadaf G, Sharma, Sanjib K, Shaw, Jonathan E, Shibuya, Kenji, Shin, Dong Wook, Shin, Youchan, Si-Ramlee, Khairil, Siantar, Rosalynn, Sibai, Abla M, Santos Silva, Diego Augusto, Simon, Mary, Simons, Judith, Simons, Leon A, Sjöström, Michael, Skovbjerg, Sine, Slowikowska-Hilczer, Jolanta, Slusarczyk, Przemyslaw, Smeeth, Liam, Smith, Margaret C, Snijder, Marieke B, So, Hung-Kwan, Sobngwi, Eugène, Söderberg, Stefan, Solfrizzi, Vincenzo, Sonestedt, Emily, Song, Yi, Sørensen, Thorkild I A, Soric, Maroje, Jérome, Charles Sossa, Soumare, Aicha, Staessen, Jan A, Stathopoulou, Maria G, Stavreski, Bill, Steene-Johannessen, Jostein, Stehle, Peter, Stein, Aryeh D, Stergiou, George S, Stessman, Jochanan, Stieber, Jutta, Stöckl, Dori, Stocks, Tanja, Stokwiszewski, Jakub, Stronks, Karien, Strufaldi, Maria Wany, Sun, Chien-An, Sung, Yn-Tz, Suriyawongpaisal, Paibul, Sy, Rody G, Shyong Tai, E, Tammesoo, Mari-Lii, Tamosiunas, Abdona, Tan, Eng Joo, Tang, Xun, Tanser, Frank, Tao, Yong, Tarawneh, Mohammed Rasoul, Tarqui-Mamani, Carolina B, Tautu, Oana-Florentina, Taylor, Anne, Theobald, Holger, Theodoridis, Xenophon, Thijs, Lutgarde, Thuesen, Betina H, Tjonneland, Anne, Tolonen, Hanna K, Tolstrup, Janne S, Topbas, Murat, Topór-Madry, Roman, Tormo, María José, Torrent, Matie, Traissac, Pierre, Trichopoulos, Dimitrio, Trichopoulou, Antonia, Trinh, Oanh T H, Trivedi, Atul, Tshepo, Lechaba, Tulloch-Reid, Marshall K, Tullu, Fikru, Tuomainen, Tomi-Pekka, Tuomilehto, Jaakko, Turley, Maria L, Tynelius, Per, Tzourio, Christophe, Ueda, Peter, Ugel, Eunice E, Ulmer, Hanno, Uusitalo, Hannu M T, Valdivia, Gonzalo, Valvi, Damaskini, van der Schouw, Yvonne T, Van Herck, Koen, Van Minh, Hoang, van Rossem, Lenie, Van Schoor, Natasja M, van Valkengoed, Irene G M, Vanderschueren, Dirk, Vanuzzo, Diego, Vatten, Lar, Vega, Toma, Velasquez-Melendez, Gustavo, Veronesi, Giovanni, Monique Verschuren, W M, Verstraeten, Roosmarijn, Victora, Cesar G, Viet, Lucie, Viikari-Juntura, Eira, Vineis, Paolo, Vioque, Jesu, Virtanen, Jyrki K, Visvikis-Siest, Sophie, Viswanathan, Bharathi, Vlasoff, Tiina, Vollenweider, Peter, Voutilainen, Sari, Wade, Alisha N, Wagner, Aline, Walton, Janette, Wan Bebakar, Wan Mohamad, Wan Mohamud, Wan Nazaimoon, Wanderley, Rildo S, Wang, Ming-Dong, Wang, Qian, Wang, Ya Xing, Wang, Ying-Wei, Wannamethee, S Goya, Wareham, Nichola, Wedderkopp, Niel, Weerasekera, Deepa, Whincup, Peter H, Widhalm, Kurt, Widyahening, Indah S, Wiecek, Andrzej, Wijga, Alet H, Wilks, Rainford J, Willeit, Johann, Willeit, Peter, Williams, Emmanuel A, Wilsgaard, Tom, Wojtyniak, Bogdan, Wong-McClure, Roy A, Wong, Justin Y Y, Wong, Tien Yin, Woo, Jean, Giwercman Wu, Aleksander, Wu, Frederick C, Wu, Shouling, Xu, Haiquan, Yan, Weili, Yang, Xiaoguang, Ye, Xingwang, Yiallouros, Panayiotis K, Yoshihara, Akihiro, Younger-Coleman, Novie O, Yusoff, Ahmad Faudzi, Zainuddin, Ahmad Ali, Zambon, Sabina, Zampelas, Antoni, Zdrojewski, Tomasz, Zeng, Yi, Zhao, Dong, Zhao, Wenhua, Zheng, Wei, Zheng, Yingfeng, Zhu, Dan, Zhussupov, Baurzhan, Zimmermann, Esther, Cisneros, Julio Zuñiga, The State Key Laboratory of Cell Biology [Shanghai, China] (CAS Center for Excellence in Molecular Cell Science), Shanghai Institute of Biochemistry and Cell Biology [Shanghai, China]-University of Chinese Academy of Sciences [Shanghai, China], Imperial College London, University of Kentucky, Middlesex University, Cleveland Clinic, Universidad Peruana Cayetano Heredia (UPCH), Brandeis University, Mulago Hospital [Kampala, Ouganda], Department of Epidemiology and Public Health, Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), World Health Organisation (WHO), Al-Quds University, Discipline of Medicine, University of South Australia [Adelaide], Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán - National Institute of Medical Science and Nutrition Salvador Zubiran [Mexico], Leibniz Institute for Prevention Research and Epidemiology - BIPS, Leibniz Association, Centre for Industrial Management, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Institute of Preventive Medicine, Copenhagen University Hospitals, School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Dept. Atherosclerose, University of Iceland [Reykjavik], Institute for Biotechnology and Bioengineering (IBB), Technical University of Lisbon, Medical University of Łódź (MUL), Department of Preventive Medicine and Public Health, Universidad Autónoma de Madrid (UAM), Faculté de Médecine de Tunis, Université de Tunis El Manar (UTM), Sunder Lal Jain Hospital, Ufa Eye Research Institute [Bashkortostan], National Institute of Public Health, Department of Epidemiology, Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke (DifE), Leibniz Association-Leibniz Association, CHU Toulouse [Toulouse], Institute of Social and Preventive Medicine, Lausanne university hospital, Division of Clinical Epidemiology and Aging Research, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department of Medical Sciences [Turin, Italy] (DMS), Università degli studi di Torino = University of Turin (UNITO), ASU - School for Engineering of Matter, Transport and Energy, Arizona State University [Tempe] (ASU), Universidade do Porto = University of Porto, University of Oxford [Oxford], Cancer & Radiation Epidemiology Unit, Gertner Institute, Chaim Sheba Medical Center, Consorcio de Investigación Biomédica en Red especializado en Epidemiología y Salud Pública (CIBERESP), Los Centros de Investigación Biomédica en Red (CIBER), 2nd Department of Internal Medicine, Molecular Medicine, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-IRC KULAK, Department of Public Health, State University of Ghent, MRC Lifecourse Epidemiology Unit [Southampton, UK], University of Southampton, Réseau International des Instituts Pasteur (RIIP), Institute of Epidemiology [Neuherberg] (EPI), German Research Center for Environmental Health - Helmholtz Center München (GmbH), Sahlgrenska University Hospital [Gothenburg], Institute of Metabolic Science, MRC, Institut National de Nutrition et de Technologie Alimentaire (INNTA), University of Huddersfield, IMIM-Hospital del Mar, Generalitat de Catalunya, Medstar Research Institute, Queen's University [Belfast] (QUB), Medical Research Council, Applied Sciences, National Research Institute on Food and Nutrition, Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Infectious diseases division, Department of internal medicine, Washington University in Saint Louis (WUSTL), Innsbruck Medical University [Austria] (IMU), Department of Epidemiology [Rotterdam], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Laboratoire d'Etude des Mammifères Marins (LEMM), Océanopolis [Brest], Faculté de Médecine Henri Warembourg - Université de Lille, Institute of Sport Science and Clinical Biomechanics, University of Southern Denmark (SDU), Icelandic Heart Association, Heart Preventive Clinic and Research Institute, Centro Investig Quim Aplicada, Coahuila, Mexico, Centro Investigacion en Quimica Aplicada, Coahuila, Mexico, University of Geneva [Switzerland], Department of Civil Engineering [Hamirpur], National Institute of Technology [Hamirpur], Health Services Research Unit, Danish Cancer Society, Institute of Cancer Epidemiology, London School of Hygiene and Tropical Medicine (LSHTM), University College of London [London] (UCL), The Georges Institute for International Health, The University of Sydney, School of Information Technology, Deakin University Waurn Ponds, Faculté de Médecine, Université Djilali Liabès [Sidi-Bel-Abbès], Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), CIBER de Epidemiología y Salud Pública (CIBERESP), VU University Medical Center [Amsterdam], Universiteit Gent = Ghent University [Belgium] (UGENT), Faculty of Agricultural and Food Science, American University of Beirut [Beyrouth] (AUB), Åbo Akademi University [Turku], Department of Public Health Sciences, Karolinska Institutet [Stockholm], Great Lakes Institute for Environmental Research, University of Windsor [Ca], Universität Heidelberg [Heidelberg], Research Center for Prevention and Health, University of Ljubljana, Division of Cancer Epidemiology, University of Crete School of medicine, School of Public Health and Clinical Nutrition, University of Eastern Finland, Institute of Epidemiology and Social Medicine, Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Research Institute of Child Nutrition Dortmund, Rheinische Friedrich-Wilhelms-Universität Bonn, Cancer Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge [UK] (CAM), Department of Oncology, University of Tampere Medical School, University of Tampere, Wageningen University and Research [Wageningen] (WUR), Centre for Environmental Health, National Institue of Public Health, School of Public Health, The University of Hong Kong (HKU), Tehran University of Medical Sciences, Istituto Nazionale di Ricerca per gli Alimenti e la Nutrizione (INRAN), INRAN, National University of Singapore (NUS), Faculty of Medicine and Life Sciences [Tampere], University of Tampere [Finland], Centre Européen de Réalité Virtuelle (CERV), École Nationale d'Ingénieurs de Brest (ENIB), Uppsala Universitet [Uppsala], Department of Public Health and Community Medicine, University of Gothenburg (GU), Institute of Earthquake Science, CEA, Beijing, CEA, Beijing, University of Porto Medical School, Laboratoire de Chimie Physique D'Orsay (LCPO), Université Paris-Sud - Paris 11 (UP11)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Aging Program, National research council, Padua, Italy, Baker IDI Heart and Diabetes Institute, Institute of Internal Medicine, Russian Academy of Medical Sciences, Department of Nutrition and Dietetics, Harokopio University, Emory University [Atlanta, GA], Départment of Biotechnology, Faculty of Science, University of Oran Es-Senia [Oran] | Université d'Oran Es-Senia [Oran], Institut National de la Santé et de la Recherche Médicale (INSERM), University of Tartu, Department of Community, Université Ain Shams-Faculty of Medicine-Environmental and Occupational Medicine, Pécsi Tudemányegyetem, Department of Community, Environmental and Occupational Medicine, Université Ain Shams, Research Centre in Physical Activity, Health and Leisure, Nutrition and Metabolism Section, International Agency for Research on Cancer, Bushehr University of Medical Sciences, Institute of Epidemiology and Medical Biometry [Ulm, Allemagne], Universität Ulm - Ulm University [Ulm, Allemagne], Università degli studi di Palermo - University of Palermo, MRc Environmental Epidemiology Unit, Department of Cardiology and Department of Clinical Epidemiology, Aarhus University Hospital, Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Department of Epidemiology and Population Studies, Jagiellonian University, Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO, Social Robotics Laboratory, University of Freiburg, Freiburg im Breisgau, Department of Ophthalmology, Universitätsklinikum Mannheim, Medizinische Fakultät Mannheim der Universität Heidelberg, University of Bari Aldo Moro (UNIBA), Department of Cardiology, Eastbourne General Hospital, Julius Center for Health Sciences and Primary Care, University Medical Center [Utrecht], Laboratoire d'Innovation pour les Technologies des Energies Nouvelles et les nanomatériaux (LITEN), Institut National de L'Energie Solaire (INES), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), King‘s College London, Public Health Sciences, University of Edinburgh, Movement Disorders and Tourette Centre, Genetica medicala, Victor Babeş University of Medicine and Pharmacy (UMFT), Andrology Unit, United Laboratories of Tartu University Clinics, Tampere University Hospital, Department of Hygiene and Epidemiology, Dept of Epidemiology and Public Health, Department of Epidemiology and Biostatistics, Imperial College London-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU), Department of Emergency and Cardiovascular Medicine, Sahlgrenska Academy, Institut de Veille Sanitaire (INVS), Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain, parent, Department of Chronic Disease Prevention, National Institute for Health and Welfare [Helsinki], University of São Paulo (USP), Institut de Recherche pour le Développement (IRD [France-Sud]), Institute for plasma research, Institute for Plasma Research, Department of Biosciences and Nutrition, Department of Reproductive Endocrinology, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam UMC - Academic medical center, Central Hospital and Faculty of medicine and biomedical sciences university, University of Yaoundé [Cameroun], Department of Clinical Sciences, Lund University [Lund]-Lund University Diabetes Centre, School of Computing [Leeds], University of Leeds, Copenhagen University Hospital, Neuroépidémiologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Maastricht University [Maastricht], Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Applied Food Science, Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, University of Amsterdam, Dept. of Social Medecine, Department of Medical Sciences and Uppsala Clinical Research Center, Uppsala University Hospital, Africa Centre for Health and Population Studies, University of KwaZulu-Natal [Durban, Afrique du Sud] (UKZN)-Medical Research Council of South Africa, Center for Family and Community Medicine, Department of Neurobiology, Care Sciences and Society, Department of Cardiovascular Sciences [Leuven], Cancer Epidemiology Institute, Department of Epidemiology and Health Promotion (MONICA Data Centre), National Public Health Institute, Nutrition et Alimentation des Populations aux Suds (NutriPass), Université Montpellier 1 (UM1)-Institut de Recherche pour le Développement (IRD)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Havard School of Public Health, Dept of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School [Athens], University of Kuopio, Tampere University, University Medical Centre Utrecht, Department of Social Medicine, Amsterdam, Center for Metabolic Bone Diseases, Catholic University of Leuven, Norwegian University of Science and Technology [Trondheim] (NTNU), Norwegian University of Science and Technology (NTNU), Universidad Miguel Hernández [Elche] (UMH), Institute of Public Health and Clinical Nutrition [Kuopio, Finland], Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Division of Community Health Sciences, St George's University of London, Medizinische Universität Wien = Medical University of Vienna, Medical University of Silesia (SUM), National Institute for Public Health and the Environment [Bilthoven] (RIVM), University of Innsbruck, National Institute of Hygiene Warsaw, Johns Hopkins University School of Medicine [Baltimore], Food Science and Technology, Beijing Forestry University, College of Automation Engineering, Nanjing University of Aeronautics and Astronautics (CAE-NUAA), NUAA, Chinese Center for Disease Control and Prevention, Department of Applied Mathematics, School of Science, Northwestern Polytechnical University, Xi’an, Shaanxi 710072, Siemens Corporate Research, Siemens AG [Munich], Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), This work was supported by the Wellcome Trust [101506/Z/13/Z]., NCD Risk Factor Collaboration (NCD-RisC). We thank WHO country and regional offices and the World Heart Federation for support in data identification and access., Universidad Autonoma de Madrid (UAM), University of Turin, Universidade do Porto, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Lille 2 - Faculté de Médecine, Westfälische Wilhelms-Universität Münster (WWU), Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), University of KwaZulu-Natal (UKZN)-Medical Research Council of South Africa, Institut de Recherche pour le Développement (IRD)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Montpellier (UM), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Lund University Diabetes Centre-Lund University [Lund], Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Medical University of Silesia, Katowice, Apollo - University of Cambridge Repository, University of Kentucky (UK), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Lausanne University Hospital, University of Oxford, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Université de Genève = University of Geneva (UNIGE), Deakin University [Waurn Ponds], Universiteit Gent = Ghent University (UGENT), Universität Heidelberg [Heidelberg] = Heidelberg University, Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Universidade de São Paulo = University of São Paulo (USP), Lund University [Lund], Laboratoire Chrono-environnement (UMR 6249) (LCE), Leopold Franzens Universität Innsbruck - University of Innsbruck, National Institute of Public Health - National Institute of Hygiene [Poland], Yiallouros, Panayiotis K. [0000-0002-8339-9285], Giampaoli, Simona [0000-0002-6679-1488], Moschonis, George [0000-0003-3009-6675], Papandreou, Dimitrios [0000-0002-4923-484X], Stathopoulou, Maria G. [0000-0003-4376-2083], Stergiou, George S. [0000-0002-6132-0038], Trichopoulou, Antonia [0000-0002-7204-6396], Valvi, Damaskini [0000-0003-4633-229X], Chen, Z, Woodward, M, Key, T, and Smith, M
Subjects: systolic blood pressure, Settore MED/09 - Medicina Interna, blood pressure measurement, HEALTH EXAMINATION SURVEYS, Blood Pressure, Hypertension, Population Health, Global Health, Non-communicable Disease, Epidemiology, [SDV]Life Sciences [q-bio], global health, South Asia, purl.org/pe-repo/ocde/ford#3.03.09 [https], kohonnut verenpaine, Medicine and Health Sciences, middle income country, measurement method, skin and connective tissue diseases, VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Kardiologi: 771, Public, Environmental & Occupational Health, adult, Population health, public health, blood pressure regulation, Public Health, Global Health, Social Medicine and Epidemiology, Non-communicable disease, kansainvälinen vertailu, health survey, aged, female, priority journal, Blood pressure, mean arterial pressure, GLOBAL TRENDS, SODIUM-INTAKE, Life Sciences & Biomedicine, survey design, hypertension, prevalence, Global health, UNITED-STATES, URBAN COMMUNITIES, Article, SECULAR TRENDS, Middle East, Central Asia, male, disease prevalence, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, kansanterveys, blood, SYSTEMATIC ANALYSIS, human, verenpainetauti, non-communicable disease, Science & Technology, Pacific Ocean, high income country, diastolic blood pressure, Pacific Rim, Blood Pressure - Epidemiology - Population, North Africa, major clinical study, HYPERTENSION PREVALENCE, verenpaine, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, ARTERIAL-HYPERTENSION, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, POTASSIUM INTAKE, sense organs, trend analysis, trend study, population research, population health, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, low income country
Abstract: Background: Change in the prevalence of raised blood pressure could be due to both shifts in the entire distribution of blood pressure (representing the combined effects of public health interventions and secular trends) and changes in its high-blood-pressure tail (representing successful clinical interventions to control blood pressure in the hypertensive population). Our aim was to quantify the contributions of these two phenomena to the worldwide trends in the prevalence of raised blood pressure. Methods: We pooled 1018 population-based studies with blood pressure measurements on 88.6 million participants from 1985 to 2016. We first calculated mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP) and prevalence of raised blood pressure by sex and 10-year age group from 20-29 years to 70-79 years in each study, taking into account complex survey design and survey sample weights, where relevant. We used a linear mixed effect model to quantify the association between (probit-transformed) prevalence of raised blood pressure and age-group-and sex-specific mean blood pressure. We calculated the contributions of change in mean SBP and DBP, and of change in the prevalence-mean association, to the change in prevalence of raised blood pressure. Results: In 2005-16, at the same level of population mean SBP and DBP, men and women in South Asia and in Central Asia, the Middle East and North Africa would have the highest prevalence of raised blood pressure, and men and women in the high-income Asia Pacific and high-income Western regions would have the lowest. In most region-sex-age groups where the prevalence of raised blood pressure declined, one half or more of the decline was due to the decline in mean blood pressure. Where prevalence of raised blood pressure has increased, the change was entirely driven by increasing mean blood pressure, offset partly by the change in the prevalence-mean association. Conclusions: Change in mean blood pressure is the main driver of the worldwide change in the prevalence of raised blood pressure, but change in the high-blood-pressure tail of the distribution has also contributed to the change in prevalence, especially in older age groups., This work was supported by the Wellcome Trust [101506/Z/13/Z].
Published: 2018

33. Age at puberty and risk of asthma: A Mendelian randomisation study

Author: James Potts, Osama Mahmoud, Miguel Pereira, John F. Thompson, Raquel Granell, Jack Bowden, Diana A van der Plaat, Bénédicte Leynaert, John Henderson, George Davey Smith, Cosetta Minelli, Deborah Jarvis, Nuala A. Sheehan, Andre F.S. Amaral, Population Health and Occupational Disease [Londres, Royaume-Uni], National Heart and Lung Institute [Londres, Royaume-Uni] (NHLI), Imperial College London-Imperial College London, Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), MRC Integrative Epidemiology Unit [Bristol, Royaume-Uni] (MRC IEU), University of Bristol [Bristol], Population Health Sciences [Bristol, Royaume-Uni], Department of Health Sciences [Leicester], University of Leicester, This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 633212. RG, JB, JH and GDS work within the Medical Research Council Integrative Epidemiology Unit at the University of Bristol, which is supported by the Medical Research Council (MC_UU_12013/1)., European Project: 633212,H2020,H2020-PHC-2014-two-stage,ALEC(2015), Bodescot, Myriam, Aging Lungs in European Cohorts - ALEC - - H20202015-05-01 - 2019-04-30 - 633212 - VALID, National Heart & Lung Institute Foundation, and Commission of the European Communities
Subjects: 0301 basic medicine, Male, puberty, Pediatric Obesity, Pulmonology, Physiology, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Body Mass Index, Endocrinology, Mathematical and Statistical Techniques, Reproductive Physiology, Odds Ratio, Medicine and Health Sciences, genetics, 11 Medical and Health Sciences, ASSOCIATIONS, Confounding, OBSERVATIONAL EPIDEMIOLOGY, Age Factors, General Medicine, Genomics, Middle Aged, MULTIPLE GENETIC-VARIANTS, 3. Good health, CAUSAL ODDS RATIOS, mendelian randomisation, Menopause, Physiological Parameters, Research Design, Meta-analysis, Physical Sciences, Menarche, Observational Studies, Medicine, Female, Life Sciences & Biomedicine, Statistics (Mathematics), Research Article, Adult, MENOPAUSE, Research and Analysis Methods, 03 medical and health sciences, Medicine, General & Internal, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, General & Internal Medicine, medicine, INSTRUMENTAL VARIABLES, Genetics, Genome-Wide Association Studies, Humans, Statistical Methods, Menstrual Cycle, Asthma, Aged, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Science & Technology, Endocrine Physiology, business.industry, Puberty, Body Weight, Biology and Life Sciences, Computational Biology, Human Genetics, Odds ratio, asthma, Mendelian Randomization Analysis, medicine.disease, Genome Analysis, Confidence interval, SEXUAL-MATURATION, United Kingdom, SUMMARIZED DATA, 030104 developmental biology, PROSPECTIVE COHORT, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Self Report, business, Body mass index, Mathematics, Demography, Meta-Analysis
Abstract: Background Observational studies on pubertal timing and asthma, mainly performed in females, have provided conflicting results about a possible association of early puberty with higher risk of adult asthma, possibly due to residual confounding. To overcome issues of confounding, we used Mendelian randomisation (MR), i.e., genetic variants were used as instrumental variables to estimate causal effects of early puberty on post-pubertal asthma in both females and males. Methods and findings MR analyses were performed in UK Biobank on 243,316 women using 254 genetic variants for age at menarche, and on 192,067 men using 46 variants for age at voice breaking. Age at menarche, recorded in years, was categorised as early (14); age at voice breaking was recorded and analysed as early (younger than average), normal (about average age), or late (older than average). In females, we found evidence for a causal effect of pubertal timing on asthma, with an 8% increase in asthma risk for early menarche (odds ratio [OR] 1.08; 95% CI 1.04 to 1.12; p = 8.7 × 10−5) and an 8% decrease for late menarche (OR 0.92; 95% CI 0.89 to 0.97; p = 3.4 × 10−4), suggesting a continuous protective effect of increasing age at puberty. In males, we found very similar estimates of causal effects, although with wider confidence intervals (early voice breaking: OR 1.07; 95% CI 1.00 to 1.16; p = 0.06; late voice breaking: OR 0.93; 95% CI 0.87 to 0.99; p = 0.03). We detected only modest pleiotropy, and our findings showed robustness when different methods to account for pleiotropy were applied. BMI may either introduce pleiotropy or lie on the causal pathway; secondary analyses excluding variants associated with BMI yielded similar results to those of the main analyses. Our study relies on self-reported exposures and outcomes, which may have particularly affected the power of the analyses on age at voice breaking. Conclusions This large MR study provides evidence for a causal detrimental effect of early puberty on asthma, and does not support previous observational findings of a U-shaped relationship between pubertal timing and asthma. Common biological or psychological mechanisms associated with early puberty might explain the similarity of our results in females and males, but further research is needed to investigate this. Taken together with evidence for other detrimental effects of early puberty on health, our study emphasises the need to further investigate and address the causes of the secular shift towards earlier puberty observed worldwide., Using genetic instruments, Cosetta Minelli and colleagues probe the causal nature of associations between early puberty, late puberty, and late-onset asthma., Author summary Why was this study done? Worldwide there has been a shift towards earlier puberty over time, possibly due to changes in childhood lifestyle and levels of adiposity. Early puberty has been linked to an increased risk of asthma in women, but findings are inconsistent across studies, and little research has been done in men. There is some suggestion that late puberty might also increase the risk of asthma. Studies performed so far have some methodological limitations that make it difficult to distinguish true effects from spurious findings. What did the researchers do and find? We studied the effect of age at puberty on asthma in women and men using Mendelian randomisation, an approach that exploits genetic data to overcome some limitations of classical observational studies. From the UK Biobank study, we analysed data on approximately 240,000 women and approximately 190,000 men with available genetic data and self-reported information on asthma and age at puberty (menarche for women and voice breaking for men). We found that women and men with early puberty had an increased risk of asthma of 8% and 7%, respectively. We found no evidence of a detrimental effect of late puberty on asthma. What do these findings mean? These findings, together with suggestions of other detrimental effects of early puberty on health, emphasise the importance of evaluating the overall evidence on health effects of early puberty. The similarity of findings in females and males might be explained by common biological or psychological factors related to early puberty, but further research is needed to investigate this.
Published: 2018
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34. Nutritional quality of food as represented by the FSAm-NPS nutrient profiling system underlying the Nutri-Score label and cancer risk in Europe: Results from the EPIC prospective cohort study

Author: Deschasaux, Mélanie, Huybrechts, Inge, Murphy, Neil, Julia, Chantal, Hercberg, Serge, Srour, Bernard, Kesse-Guyot, Emmanuelle, Latino-Martel, Paule, Biessy, Carine, Casagrande, Corinne, Jenab, Mazda, Ward, Heather, Weiderpass, Elisabete, Dahm, Christina C., Overvad, Kim, Kyrø, Cecilie, Olsen, Anja, Affret, Aurélie, Boutron-Ruault, Marie Christine, Mahamat-Saleh, Yahya, Kaaks, Rudolf, Kühn, Tilman, Boeing, Heiner, Schwingshackl, Lukas, Bamia, Christina, Peppa, Eleni, Trichopoulou, Antonia, Masala, Giovanna, Krogh, Vittorio, Panico, Salvatore, Tumino, Rosario, Sacerdote, Carlotta, Bueno-de-Mesquita, Bas, Peeters, Petra H., Hjartåker, Anette, Rylander, Charlotta, Skeie, Guri, Ramón Quirós, J., Jakszyn, Paula, Salamanca-Fernández, Elena, Huerta, José María, Ardanaz, Eva, Amiano, Pilar, Ericson, Ulrika, Sonestedt, Emily, Huseinovic, Ena, Johansson, Ingegerd, Khaw, Kay Tee, Wareham, Nick, Bradbury, Kathryn E., Perez-Cornago, Aurora, Tsilidis, Konstantinos K., Ferrari, Pietro, Riboli, Elio, Gunter, Marc J., Touvier, Mathilde, Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Paris 13 (UP13)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition and Metabolism Section, International Agency for Research on Cancer, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), School of Public Health [London, UK] (Faculty of Medicine), Imperial College London, Department of Community Medicine, Faculty of Health Sciences, The Arctic University of Norway (UiT), Cancer Registry of Norway, Institute of Population-Based Cancer Research, Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Genetic Epidemiology Group [Helsinki], Folkhälsan Research Center, Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki-Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, Department of Public Health, Section for Epidemiology, Aarhus University [Aarhus], Danish Cancer Society Research Center, Mode de vie, génétique et santé : études intégratives et transgénérationnelles (U1018 (Équipe 9)), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Gustave Roussy (IGR), Division of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department of Epidemiology, German Institute of Human Nutrition (DIfE), WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Dept of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School [Athens]-University of Athens Medical School [Athens], Hellenic Health Foundation, Cancer Risk Factors and LifeStyle Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], Dipartimento di Medicina Clinica e Chirurgia, University of Naples Federico II, Cancer registry and histopathology unit, Civile - M.P.Arezzo Hospital, Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital-Center for Cancer Prevention (CPO-Piemonte), Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment [Bilthoven] (RIVM), Department of Gastroenterology and Hepatology, University Medical Center [Utrecht], School of Public Health - Department of Epidemiology and Biostatistics, Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Julius Center for Health Sciences and Primary Care, Department of Nutrition [Oslo], Institute of Basic Medical Sciences [Oslo], Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Public Health Directorate Asturias, Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology, L´Hospitallet de Llobregat, Facultat de Ciències de la Salut Blanquerna, Universitat Ramon Llull [Barcelona] (URL), Escuela Andaluza de Salud Publica, Instituto de Investigación Biosanitaria de Granada (Granada.ibs), Hospitales Universitarios de Granada/Universidad de Granada, CIBER de Epidemiología y Salud Pública (CIBERESP), Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Public Health Institute of Navarra, IdiSNA, Navarra Institute for Health Research, Public Health Department of Gipuzkoa, Diabetes and Cardiovascular disease, Genetic Epidemiology, Department of Clinical Sciences, Clinical Research Center, Lund University [Lund]-Lund University [Lund], Nutritional Epidemiology, Department of Internal Medicine and Clinical Nutrition Institute of Medicine Sahlgrenska Academy, University of Gothenburg (GU), Department of Odontology, Umeå University, School of Clinical Medicine, Addenbrooke's Hospital, University of Cambridge [UK] (CAM), MRC Epidemiology Unit, Institute of Metabolic Science, Nuffield Department of Population Health - Cancer Epidemiology Unit, University of Oxford [Oxford], Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, French National Cancer Institute (INCa)-Canceropole Ile-de-France [2017-1-PL SHS-01-INSERM ADR 5-1], European Commission (DG-SANCO), Danish Cancer Society (Denmark), Ligue Contre le Cancer, (France), Institut Gustave Roussy, (France), Mutuelle Generale de l'Education Nationale, (France), Institut National de la Sante et de la Recherche Medicale (Inserm), (France), Deutsche Krebshilfe (Germany), Deutsches Krebsforschungszentrum (Germany), Federal Ministry of Education and Research (Germany), Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Dutch Ministry of Public Health, Welfare, and Sports (VWS) (the Netherlands), Netherlands Cancer Registry (NKR) (the Netherlands), LK Research Funds (the Netherlands), Dutch Prevention Funds (the Netherlands), Dutch ZON (Zorg Onderzoek Nederland) (the Netherlands), World Cancer Research Fund (WCRF) (the Netherlands), Statistics Netherlands (the Netherlands), Health Research Fund (FIS) [PI13/00061], Regional Government of Andalucia (Spain), Regional Government of Asturias (Spain), Regional Government of Basque Country (Spain), Regional Government of Murcia (Spain) [6236], Regional Government of Navarra, ISCIII RETIC (Spain) [RD06/0020], Swedish Cancer Society (Sweden), Swedish Scientific Council (Sweden), County Council of Skane (Sweden), County Council of Vasterbotten (Sweden), Cancer Research UK [14136, C570/A16491, C8221/A19170], Medical Research Council [1000143, MR/M012190/1], National Research Council (Italy), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Hôpital avicenne, Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne, Hôpital Paul Brousse-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Hôpital Paul Brousse-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Gustave Roussy (IGR), 'CIVIC-M.P. AREZZO' Hospital, University of Oxford, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR), Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Deschasaux, Mélanie [0000-0002-3359-420X], Huybrechts, Inge [0000-0003-3838-855X], Murphy, Neil [0000-0003-3347-8249], Hercberg, Serge [0000-0002-3168-1350], Srour, Bernard [0000-0002-1277-3380], Kesse-Guyot, Emmanuelle [0000-0002-9715-3534], Weiderpass, Elisabete [0000-0003-2237-0128], Dahm, Christina C [0000-0003-0481-2893], Kyrø, Cecilie [0000-0002-9083-8960], Olsen, Anja [0000-0003-4788-503X], Boutron-Ruault, Marie-Christine [0000-0002-5956-5693], Mahamat-Saleh, Yahya [0000-0002-5892-8886], Tumino, Rosario [0000-0003-2666-414X], Sacerdote, Carlotta [0000-0002-8008-5096], Hjartåker, Anette [0000-0003-3002-4030], Skeie, Guri [0000-0003-2476-4251], Jakszyn, Paula [0000-0003-0672-8847], Huerta, José María [0000-0002-9637-3869], Sonestedt, Emily [0000-0002-0747-4562], Johansson, Ingegerd [0000-0002-9227-8434], Wareham, Nick [0000-0003-1422-2993], Bradbury, Kathryn E [0000-0003-3345-7333], Perez-Cornago, Aurora [0000-0002-5652-356X], Riboli, Elio [0000-0001-6795-6080], Touvier, Mathilde [0000-0002-8322-8857], Apollo - University of Cambridge Repository, Deschasaux, Mélanie, Huybrechts, Inge, Murphy, Neil, Julia, Chantal, Hercberg, Serge, Srour, Bernard, Kesse-Guyot, Emmanuelle, Latino-Martel, Paule, Biessy, Carine, Casagrande, Corinne, Jenab, Mazda, Ward, Heather, Weiderpass, Elisabete, Dahm, Christina C, Overvad, Kim, Kyrø, Cecilie, Olsen, Anja, Affret, Aurélie, Boutron-Ruault, Marie-Christine, Mahamat-Saleh, Yahya, Kaaks, Rudolf, Kühn, Tilman, Boeing, Heiner, Schwingshackl, Luka, Bamia, Christina, Peppa, Eleni, Trichopoulou, Antonia, Masala, Giovanna, Krogh, Vittorio, Panico, Salvatore, Tumino, Rosario, Sacerdote, Carlotta, Bueno-de-Mesquita, Ba, Peeters, Petra H, Hjartåker, Anette, Rylander, Charlotta, Skeie, Guri, Ramón Quirós, J, Jakszyn, Paula, Salamanca-Fernández, Elena, Huerta, José María, Ardanaz, Eva, Amiano, Pilar, Ericson, Ulrika, Sonestedt, Emily, Huseinovic, Ena, Johansson, Ingegerd, Khaw, Kay-Tee, Wareham, Nick, Bradbury, Kathryn E, Perez-Cornago, Aurora, Tsilidis, Konstantinos K, Ferrari, Pietro, Riboli, Elio, Gunter, Marc J, and Touvier, Mathilde
Subjects: Adult, Male, [SDV.CAN]Life Sciences [q-bio]/Cancer, Nutrition Policy, Cohort Studies, Food Preferences, Medicine, General & Internal, project, Food Labeling, Risk Factors, front-of-package, su.vi.max cohort, General & Internal Medicine, Neoplasms, Humans, french adults, Prospective Studies, dietary index, database, Medicine(all), validation, Nutrition and Dietetics, Science & Technology, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762, 11 Medical And Health Sciences, Middle Aged, Näringslära, VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762, Europe, prospective association, 3121 General medicine, internal medicine and other clinical medicine, Medicine, Female, cardiovascular-disease risk, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, Life Sciences & Biomedicine, Nutritive Value, france, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: Source at https://doi.org/10.1371/journal.pmed.1002651. Background - Helping consumers make healthier food choices is a key issue for the prevention of cancer and other diseases. In many countries, political authorities are considering the implementation of a simplified labelling system to reflect the nutritional quality of food products. The Nutri-Score, a five-colour nutrition label, is derived from the Nutrient Profiling System of the British Food Standards Agency (modified version) (FSAm-NPS). How the consumption of foods with high/low FSAm-NPS relates to cancer risk has been studied in national/regional cohorts but has not been characterized in diverse European populations. Methods and findings - This prospective analysis included 471,495 adults from the European Prospective Investigation into Cancer and Nutrition (EPIC, 1992–2014, median follow-up: 15.3 y), among whom there were 49,794 incident cancer cases (main locations: breast, n = 12,063; prostate, n = 6,745; colon-rectum, n = 5,806). Usual food intakes were assessed with standardized country-specific diet assessment methods. The FSAm-NPS was calculated for each food/beverage using their 100-g content in energy, sugar, saturated fatty acid, sodium, fibres, proteins, and fruits/vegetables/legumes/nuts. The FSAm-NPS scores of all food items usually consumed by a participant were averaged to obtain the individual FSAm-NPS Dietary Index (DI) scores. Multi-adjusted Cox proportional hazards models were computed. A higher FSAm-NPS DI score, reflecting a lower nutritional quality of the food consumed, was associated with a higher risk of total cancer (HRQ5 versus Q1 = 1.07; 95% CI 1.03–1.10, P-trend < 0.001). Absolute cancer rates in those with high and low (quintiles 5 and 1) FSAm-NPS DI scores were 81.4 and 69.5 cases/10,000 person-years, respectively. Higher FSAm-NPS DI scores were specifically associated with higher risks of cancers of the colon-rectum, upper aerodigestive tract and stomach, lung for men, and liver and postmenopausal breast for women (all P < 0.05). The main study limitation is that it was based on an observational cohort using self-reported dietary data obtained through a single baseline food frequency questionnaire; thus, exposure misclassification and residual confounding cannot be ruled out. Conclusions - In this large multinational European cohort, the consumption of food products with a higher FSAm-NPS score (lower nutritional quality) was associated with a higher risk of cancer. This supports the relevance of the FSAm-NPS as underlying nutrient profiling system for front-of-pack nutrition labels, as well as for other public health nutritional measures.
Published: 2018

35. Assessment of Plasmodium Vivax Chloroquine Resistance in Cambodia (CRePViCam)

Author: National Institute of Allergy and Infectious Diseases (NIAID) and Didier Menard, Malaria Molecular Epidemiology Unit
Published: 2015

36. Osteoprotegerin and breast cancer risk by hormone receptor subtype: A nested case-control study in the EPIC cohort

Author: Miren Dorronsoro, Marc J. Gunter, Mathilde His, Helena Schock, Sabina Sieri, Maria Dolores Chirlaque, Aurélie Affret, Rudolf Kaaks, Elisabete Weiderpass, H. Bas Bueno-de-Mesquita, Philippos Orfanos, Melissa A. Merritt, Anne Tjønneland, Domenico Palli, J. Ramón Quirós, María José Sánchez, Theron Johnson, Danja Sarink, Eva Ardanaz, Antonio Agudo, Renée T. Fortner, Laure Dossus, Timothy J. Key, Kim Overvad, Rosario Tumino, Androniki Naska, Petra H.M. Peeters, Heiner Boeing, Amalia Mattiello, Anja Olsen, Sabina Rinaldi, Eiliv Lund, Antonia Trichopoulou, Carla H. van Gils, Marie-Christine Boutron-Ruault, Kay-Tee Khaw, Elio Riboli, Fulvio Ricceri, Khaw, Kay-Tee [0000-0002-8802-2903], Apollo - University of Cambridge Repository, University Medical Center Utrecht, Imperial College Trust, [Fortner,RT, Sarink,D, Schock,H, Johnson,T, Kaaks,R] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Tjønneland,A, Olsen,A] Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark. [Overvad,K] Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark. [Affret,A, His,M, Boutron-Ruault,MC] Université Paris-Saclay, Université Paris-Sud, UVSQ, CESP, INSERM, Villejuif, France. [Affret,A, Boutron-Ruault,MC] Villejuif, France. [Boeing,H] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. [Trichopoulou,A, Naska,A, Orfanos,P] Hellenic Health Foundation, Athens, Greece. [Trichopoulou,A, Orfanos,P] WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. [Palli,D] Cancer Risk Factors and Life-Style Epidemiology Unit, Cancer Research and Prevention Institute - ISPO, Florence, Italy. [Sieri,S] Epidemiology and Prevention Unit, Department of Preventive & Predictive Medicine Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Mattiello,A] Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, 'Civic - M.p.Arezzo' Hospital, ASP Ragusa, Italy. [Ricceri,F] Unit of Epidemiology, Regional Health Service ASL TO3, Grugliasco (TO), Italy. [Ricceri,F] Unit of Cancer Epidemiology, Department of Medical Sciences, University of Turin, Turin, Italy. [Bueno-de-Mesquita,HB] Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. [Bueno-de-Mesquita,HB, Merritt,MA, Riboli,E] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Bueno-de-Mesquita,HB] Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. [Peeters,PH, Van Gils,CH] Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands. [Peeters,PH] MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, UK. [Weiderpass,E, Lund,E] Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway. [Weiderpass,E] Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway. [Weiderpass,E] Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. [Weiderpass,E] Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland. [Quirós,JR] Public Health Directorate, Asturias, Spain. [Agudo,A] Unit of Nutrition and Cancer. Cancer Epidemiology Research Program. Catalan Institute of Oncology-IDIBELL. L'Hospitalet de Llobregat, Barcelona, Spain. [Sánchez,MJ] Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria ibs. GRANADA. Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain. [Sánchez,MJ, Chirlaque,MD, Ardanaz,E] CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Chirlaque,MD] Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Chirlaque,MD] Department of Health and Social Sciences, Universidad de Murcia, Murcia, Spain. [Ardanaz,E] Navarra Public Health Institute, Pamplona, Spain. [Ardanaz,E] IdiSNA, Navarra Institute for Health Research, Pamplona, Spain. [Dorronsoro,M] Public Health Direction and Biodonostia Research Institute CIBERESP, Basque Regional Health Department, San Sebastian, Spain. [Key,T] Nuffield Department of Population Health, University of Oxford, Oxford, UK. [Khaw,KT] Cancer Epidemiology Unit, University of Cambridge, Cambridge, UK. [Rinaldi,S, Dossus,L, Gunter,M] International Agency for Research on Cancer, Lyon, France., This project was funded by research grant 111454 from the Deutsche Kresbshilfe. RT Fortner was supported by a Marie Curie International Incoming Fellowship of the European Commission’s Seventh Framework Programme (MC-IIF-623984). The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by the Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, and Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, and Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and the National Research Council (Italy), the Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands (The Netherlands), ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway), Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia, and Navarra, and ISCIII RETIC (RD06/0020) (Spain), the Swedish Cancer Society, Swedish Research Council, and County Councils of Skåne and Västerbotten (Sweden), and Cancer Research UK (14136 to EPIC-Norfolk, and C570/A16491 and C8221/A19170 to EPIC-Oxford), and the Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (UK).
Subjects: 0301 basic medicine, Oncology, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Transcription Factors::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid::Receptors, Progesterone [Medical Subject Headings], Estrogen receptor, Progesterone receptor, Cohort Studies, 0302 clinical medicine, Breast cancer, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Immunologic::Receptors, Cytokine::Receptors, Tumor Necrosis Factor::Receptor Activator of Nuclear Factor-kappa B [Medical Subject Headings], Risk Factors, Prospective Studies, Prospective cohort study, Medicine(all), Osteoprotegerina, biology, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, 11 Medical And Health Sciences, General Medicine, Middle Aged, Necrosi, 3. Good health, European Prospective Investigation into Cancer and Nutrition, RANK axis, RANKL, 030220 oncology & carcinogenesis, Neoplasias de la mama, Female, Research Article, musculoskeletal diseases, medicine.medical_specialty, Receptores estrogénicos, Health Care::Environment and Public Health::Public Health::Epidemiologic Factors::Causality::Risk Factors [Medical Subject Headings], Breast Neoplasms, Receptores de progesterona, Receptores de hormonas, Hormone receptor, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::DNA-Binding Proteins::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid::Receptors, Estrogen [Medical Subject Headings], Càncer de mama, Health Care::Environment and Public Health::Public Health::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings], Necrosis, 03 medical and health sciences, Osteoprotegerin, General & Internal Medicine, Internal medicine, Journal Article, medicine, Humans, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], business.industry, Case-control study, medicine.disease, Health Care::Environment and Public Health::Public Health::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Prospective Studies [Medical Subject Headings], 030104 developmental biology, Endocrinology, Case-Control Studies, Nested case-control study, Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Climacteric::Menopause::Postmenopause [Medical Subject Headings], biology.protein, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Immunologic::Receptors, Cytokine::Receptors, Tumor Necrosis Factor::Tumor Necrosis Factor Decoy Receptors::Osteoprotegerin [Medical Subject Headings], VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business
Abstract: All Author: Renée T. Fortner, Danja Sarink, Helena Schock, Theron Johnson, Anne Tjønneland, Anja Olsen, Kim Overvad, Aurélie Affret, Mathilde His, Marie-Christine Boutron-Ruault, Heiner Boeing, Antonia Trichopoulou, Androniki Naska, Philippos Orfanos, Domenico Palli, Sabina Sieri, Amalia Mattiello, Rosario Tumino, Fulvio Ricceri, H. Bas Bueno-de-Mesquita, Petra H. M. Peeters, Carla H. Van Gils, Elisabete Weiderpass, Eiliv Lund, J. Ramón Quirós, Antonio Agudo, Maria-José Sánchez, María-Dolores Chirlaque, Eva Ardanaz, Miren Dorronsoro, Tim Key, Kay-Tee Khaw, Sabina Rinaldi, Laure Dossus, Marc Gunter, Melissa A. Merritt, Elio Riboli and Rudolf Kaaks, Background: Circulating osteoprotegerin (OPG), a member of the receptor activator of nuclear factor kappa-B (RANK) axis, may influence breast cancer risk via its role as the decoy receptor for both the RANK ligand (RANKL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Circulating OPG and breast cancer risk has been examined in only one prior study. Methods: A case-control study was nested in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 2008 incident invasive breast cancer cases (estrogen receptor (ER)+, n = 1622; ER–, n = 386), matched 1:1 to controls, were included in the analysis. Women were predominantly postmenopausal at blood collection (77%); postmenopausal women included users and non-users of postmenopausal hormone therapy (HT). Serum OPG was quantified with an electrochemiluminescence assay. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. Results: The associations between OPG and ER+ and ER– breast cancer differed significantly. Higher concentrations of OPG were associated with increased risk of ER– breast cancer (top vs. bottom tertile RR = 1.93 [95% CI 1.24–3.02]; ptrend = 0.03). We observed a suggestive inverse association for ER+ disease overall and among women premenopausal at blood collection. Results for ER– disease did not differ by menopausal status at blood collection (phet = 0.97), and we observed no heterogeneity by HT use at blood collection (phet ≥ 0.43) or age at breast cancer diagnosis (phet ≥ 0.30). Conclusions: This study provides the first prospective data on OPG and breast cancer risk by hormone receptor subtype. High circulating OPG may represent a novel risk factor for ER– breast cancer., This project was funded by research grant 111454 from the Deutsche Kresbshilfe. RT Fortner was supported by a Marie Curie International Incoming Fellowship of the European Commission’s Seventh Framework Programme (MC-IIF-623984). The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by the Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, and Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and the National Research Council (Italy); the Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands (The Netherlands); ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia, and Navarra, and ISCIII RETIC (RD06/0020) (Spain); the Swedish Cancer Society, Swedish Research Council, and County Councils of Skåne and Västerbotten (Sweden); and Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), and the Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (UK).
Published: 2017

37. Does the low prevalence affect the sample size of interventional clinical trials of rare diseases? An analysis of data from the aggregate analysis of clinicaltrials.gov

Author: Jason Madan, Catrin Tudur Smith, Martin Posch, Nigel Stallard, Sarah Zohar, Siew Wan Hee, Frank Miller, Simon Day, Adrian Willis, Statistics and Epidemiology Unit [Coventry, UK] (Division of Health Sciences), University of Warwick [Coventry]-Warwick Medical School, University of Warwick [Coventry], Warwick Clinical Trials Unit [Coventry, UK] (Division of Health Sciences), Department of Biostatistics [Liverpool, UK], North West Hub for Trials Methodology Research [Liverpool, UK], University of Liverpool-University of Liverpool, Clinical Trials Consulting and Training Limited [Buckingham, UK], University of Buckingham [UK], Department of Statistics [Stockholm], Stockholm University, Section of Medical Statistics [Vienna, Austria] (CeMSIIS), Medizinische Universität Wien = Medical University of Vienna, Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Warwick Medical School, University of Warwick [Coventry]-University of Warwick [Coventry], University of Warwick [Coventry, UK]-Warwick Medical School, Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Statistics and Epidemiology Unit [Coventry, UK] ( Division of Health Sciences ), Warwick Medical School [Coventry, U.K.]-University of Warwick [Coventry, UK], Warwick Clinical Trials Unit [Coventry, UK] ( Division of Health Sciences ), University of Liverpool [Liverpool, UK]-University of Liverpool [Liverpool, UK], Section of Medical Statistics [Vienna, Austria] ( CeMSIIS ), Medical University of Vienna [Austria], Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), and BMC, BMC
Subjects: medicine.medical_specialty, [SDV]Life Sciences [q-bio], Prevalence, Orphadata, Disease, Multiple linear regression model, Orphan drug, 03 medical and health sciences, Rare Diseases, 0302 clinical medicine, Aggregate analysis of clinialtrials.gov, Internal medicine, medicine, Humans, Genetics(clinical), Pharmacology (medical), 030212 general & internal medicine, Orphanet, Genetics (clinical), Medicine(all), Clinical Trials as Topic, Internet, [ SDV ] Life Sciences [q-bio], business.industry, Sample size, Research, General Medicine, R1, 3. Good health, [SDV] Life Sciences [q-bio], Clinical trial, Aggregate analysis, Orphan disease, Sample size determination, business, Rare disease, 030217 neurology & neurosurgery, RC
Abstract: Background: Clinical trials are typically designed using the classical frequentist framework to constrain type I and II error rates. Sample sizes required in such designs typically range from hundreds to thousands of patients which can be challenging for rare diseases. It has been shown that rare disease trials have smaller sample sizes than non-rare disease trials. Indeed some orphan drugs were approved by the European Medicines Agency based on studies with as few as 12 patients. However, some studies supporting marketing authorisation included several hundred patients. In this work, we explore the relationship between disease prevalence and other factors and the size of interventional phase 2 and 3 rare disease trials conducted in the US and/or EU. We downloaded all clinical trials from Aggregate Analysis of ClinialTrials.gov (AACT) and identified rare disease trials by cross-referencing MeSH terms in AACT with the list from Orphadata. We examined the effects of prevalence and phase of study in a multiple linear regression model adjusting for other statistically significant trial characteristics.Results: Of 186941 ClinicalTrials.gov trials only 1567 (0.8%) studied a single rare condition with prevalence information from Orphadata. There were 19 (1.2%) trials studying disease with prevalence Conclusions: We found that prevalence was associated with the size of phase 3 trials with trials of rarer diseases noticeably smaller than the less rare diseases trials where phase 3 rarer disease (prevalence
Published: 2016

38. Advanced hybrid closed loop therapy versus conventional treatment in adults with type 1 diabetes (ADAPT): a randomised controlled study

Author: Pratik Choudhary, Ralf Kolassa, Winfried Keuthage, Jens Kroeger, Charles Thivolet, Mark Evans, Roseline Ré, Simona de Portu, Linda Vorrink, John Shin, Aklilu Habteab, Javier Castañeda, Julien da Silva, Ohad Cohen, King‘s College London, NHS Foundation Trust [London], The Royal Marsden, University of Leicester, Diabetologische Schwerpunktpraxis [Bergheim, Germany] (DS), Schwerpunktpraxis für Diabetes und Ernährungsmedizin [Münster, Germany] (SDE), Zentrum für Diabetologie Bergedorf [Hamburg, Germany] (ZDB), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hospices Civils de Lyon (HCL), MRC Epidemiology Unit [Cambridge, UK] (Wellcome Trust-MRC Institute of Metabolic Science), University of Cambridge [UK] (CAM)-Addenbrooke’s Hospital [Cambridge, UK]-Wellcome Trust-MRC Institute of Metabolic Science (IMS), Medtronic Diabetes, International Trading Sàrl [Tolochenaz, Switzerland ] (MDITS), Medtronic [Northridge, CA, USA] (Mt), Medtronic Bakken Research Center BV, Institut de Ciencies del Cosmos (ICCUB), Universitat de Barcelona (UB), ADAPT study Group, and CarMeN, laboratoire
Subjects: Adult, Blood Glucose, Glycated Hemoglobin, Blood Glucose Self-Monitoring, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Diabetic Ketoacidosis, [SDV] Life Sciences [q-bio], Diabetes Mellitus, Type 1, Treatment Outcome, Endocrinology, Internal Medicine, Humans, Hypoglycemic Agents, Insulin, Prospective Studies
Abstract: International audience; BACKGROUND: Adults with type 1 diabetes who are treated with multiple daily injections of insulin plus intermittently scanned continuous glucose monitoring (isCGM) can have suboptimal glucose control. We aimed to assess the efficacy of an advanced hybrid closed loop (AHCL) system compared with such therapy in this population. METHODS: The Advanced Hybrid Closed Loop Study in Adult Population with Type 1 Diabetes (ADAPT) trial is a prospective, multicentre, open-label, randomised controlled trial that involved 14 centres in three European countries (France, Germany, and the UK). We enrolled patients who were at least 18 years of age, had a type 1 diabetes duration of at least 2 years, HbA(1c) of at least 8% (64 mmol/mol), and were using multiple daily injections of insulin plus isCGM (cohort A) or real time continuous glucose monitoring (cohort B) for at least 3 months. Here, only results for cohort A are reported. Participants were randomly allocated 1:1 to AHCL therapy or continuation of multiple daily injections of insulin plus continuous glucose monitoring for 6 months with an investigator-blinded block randomisation procedure. Participants and treating clinicians could not be masked to the arm assignment. The primary endpoint was the between-group difference in mean HbA(1c) change from baseline to 6 months in the intention-to-treat population using AHCL therapy and those using multiple daily injections of insulin plus isCGM. The primary endpoint was analysed using a repeated measures random-effects model with the study arm and period as factors. Safety endpoints included the number of device deficiencies, severe hypoglycaemic events, diabetic ketoacidosis, and serious adverse events. This study is registered with ClinicalTrials.gov, NCT04235504. FINDINGS: Between July 13, 2020, and March 12, 2021, 105 people were screened and 82 randomly assigned to treatment (41 in each arm). At 6 months, mean HbA(1c) had decreased by 1·54% (SD 0·73), from 9·00% to 7·32% in the AHCL group and 0·20% (0·80) in the multiple daily injections of insulin plus isCGM from 9·07% to 8·91% (model-based difference -1·42%, 95% CI -1·74 to -1·10; p\textless0·0001). No diabetic ketoacidosis, severe hypoglycaemia, or serious adverse events related to study devices occurred in either group; two severe hypoglycaemic events occurred in the run-in phase. 15 device-related non-serious adverse events occurred in the AHCL group, compared with three in the multiple daily injections of insulin plus isCGM group. Two serious adverse events occurred (one in each group), these were breast cancer (in one patient in the AHCL group) and intravitreous haemorrhage (in one patient in the multiple daily injections of insulin plus isCGM group). INTERPRETATION: In people with type 1 diabetes using multiple daily injections of insulin plus isCGM and with HbA(1c) of at least 8%, the use of AHCL confers benefits in terms of glycaemic control beyond those that can be achieved with multiple daily injections of insulin plus isCGM. These data support wider access to AHCL in people with type 1 diabetes not at target glucose levels. FUNDING: Medtronic International Trading Sàrl.
Published: 2022

39. Infant BCG vaccination and risk of pulmonary and extrapulmonary tuberculosis throughout the life course: a systematic review and individual participant data meta-analysis

Author: Leonardo Martinez, Olivia Cords, Qiao Liu, Carlos Acuna-Villaorduna, Maryline Bonnet, Greg J Fox, Anna Cristina C Carvalho, Pei-Chun Chan, Julio Croda, Philip C Hill, Elisa Lopez-Varela, Simon Donkor, Katherine Fielding, Stephen M Graham, Marcos A Espinal, Beate Kampmann, Arthur Reingold, Helena Huerga, Julian A Villalba, Louis Grandjean, Giovanni Sotgiu, Uzochukwu Egere, Sarman Singh, Limei Zhu, Christian Lienhardt, Justin T Denholm, James A Seddon, Christopher C Whalen, Alberto L García-Basteiro, Rina Triasih, Cheng Chen, Jitendra Singh, Li-Min Huang, Surendra Sharma, Djohar Hannoun, Helena del Corral, Anna M Mandalakas, LaShaunda L Malone, Du-Lin Ling, Afrânio Kritski, Catherine M Stein, Richa Vashishtha, Fadila Boulahbal, Chi-Tai Fang, W Henry Boom, Eduardo Martins Netto, Antonio Carlos Lemos, Anneke C Hesseling, Alexander Kay, Edward C Jones-López, C Robert Horsburgh, Christoph Lange, Jason R Andrews, Boston University [Boston] (BU), University of California (UC), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP), University of Nottingham, UK (UON), Infectious Diseases Epidemiology Unit, London School of Hygiene and Tropical Medicine (LSHTM), Medical Research Council Unit The Gambia (MRC), Imperial College London, and Universidad Peruana Cayetano Heredia (UPCH)
Subjects: Adult, Adolescent, MESH: Child, Humans, Tuberculosis, MESH: Tuberculosis, Child, Tuberculosis, Pulmonary, Aged, Retrospective Studies, MESH: Adolescent, MESH: Tuberculosis, Pulmonary, MESH: Aged, MESH: Humans, Vaccination, MESH: Child, Preschool, MESH: Infant, Newborn, Infant, Newborn, Infant, MESH: Adult, MESH: Retrospective Studies, MESH: Vaccination, General Medicine, MESH: Infant, MESH: BCG Vaccine, Child, Preschool, BCG Vaccine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract: BACKGROUND: BCG vaccines are given to more than 100 million children every year, but there is considerable debate regarding the effectiveness of BCG vaccination in preventing tuberculosis and death, particularly among older children and adults. We therefore aimed to investigate the age-specific impact of infant BCG vaccination on tuberculosis (pulmonary and extrapulmonary) development and mortality. METHODS: In this systematic review and individual participant data meta-analysis, we searched MEDLINE, Web of Science, BIOSIS, and Embase without language restrictions for case-contact cohort studies of tuberculosis contacts published between Jan 1, 1998, and April 7, 2018. Search terms included "mycobacterium tuberculosis", "TB", "tuberculosis", and "contact". We excluded cohort studies that did not provide information on BCG vaccination or were done in countries that did not recommend BCG vaccination at birth. Individual-level participant data for a prespecified list of variables, including the characteristics of the exposed participant (contact), the index case, and the environment, were requested from authors of all eligible studies. Our primary outcome was a composite of prevalent (diagnosed at or within 90 days of baseline) and incident (diagnosed more than 90 days after baseline) tuberculosis in contacts exposed to tuberculosis. Secondary outcomes were pulmonary tuberculosis, extrapulmonary tuberculosis, and mortality. We derived adjusted odds ratios (aORs) using mixed-effects, binary, multivariable logistic regression analyses with study-level random effects, adjusting for the variable of interest, baseline age, sex, previous tuberculosis, and whether data were collected prospectively or retrospectively. We stratified our results by contact age and Mycobacterium tuberculosis infection status. This study is registered with PROSPERO, CRD42020180512. FINDINGS: We identified 14 927 original records from our database searches. We included participant-level data from 26 cohort studies done in 17 countries in our meta-analysis. Among 68 552 participants, 1782 (2·6%) developed tuberculosis (1309 [2·6%] of 49 686 BCG-vaccinated participants vs 473 [2·5%] of 18 866 unvaccinated participants). The overall effectiveness of BCG vaccination against all tuberculosis was 18% (aOR 0·82, 95% CI 0·74-0·91). When stratified by age, BCG vaccination only significantly protected against all tuberculosis in children younger than 5 years (aOR 0·63, 95% CI 0·49-0·81). Among contacts with a positive tuberculin skin test or IFNγ release assay, BCG vaccination significantly protected against tuberculosis among all participants (aOR 0·81, 95% CI 0·69-0·96), participants younger than 5 years (0·68, 0·47-0·97), and participants aged 5-9 years (0·62, 0·38-0·99). There was no protective effect among those with negative tests, unless they were younger than 5 years (0·54, 0·32-0·90). 14 cohorts reported on whether tuberculosis was pulmonary or extrapulmonary (n=57 421). BCG vaccination significantly protected against pulmonary tuberculosis among all participants (916 [2·2%] in 41 119 vaccinated participants vs 334 [2·1%] in 16 161 unvaccinated participants; aOR 0·81, 0·70-0·94) but not against extrapulmonary tuberculosis (106 [0·3%] in 40 318 vaccinated participants vs 38 [0·2%] in 15 865 unvaccinated participants; 0·96, 0·65-1·41). In the four studies with mortality data, BCG vaccination was significantly protective against death (0·25, 0·13-0·49). INTERPRETATION: Our results suggest that BCG vaccination at birth is effective at preventing tuberculosis in young children but is ineffective in adolescents and adults. Immunoprotection therefore needs to be boosted in older populations. FUNDING: National Institutes of Health.
Published: 2022

40. Plasma phospholipid long-chain n-3 polyunsaturated fatty acids and body weight change

Author: Giovanna Tagliabue, Ingegerd Johansson, José María Huerta, Domenico Palli, Anne Tjønneland, Petra H.M. Peeters, Aurelio Barricarte, Anne M. May, Göran Hallmans, Francesca L. Crowe, Madlen Schütze, Daphne L. van der A, Françoise Clavel-Chapelon, Birgit Teucher, George Makrygiannis, Thorkild I. A. Sørensen, Jonas Manjer, Isabelle Romieu, Laudina Rodríguez, H. B. Bueno-de-Mesquita, Veronique Chajes, Kim Overvad, Guy Fagherazzi, Nadia Slimani, Karen Margrete Due, Nicholas J. Wareham, Dimosthenis Zylis, Heiner Boeing, Pilar Amiano, Kay-Tee Khaw, Claus Dethlefsen, Amalia Mattiello, Marianne Uhre Jakobsen, Rudolf Kaaks, Jytte Halkjær, Marie-Christine Boutron-Ruault, Elisabet Wirfält, Esther Molina-Montes, Noémie Travier, Elio Riboli, Antonia Trichopoulou, [Jakobsen,MU] Department of Clinical Epidemiology. [Jakobsen,MU, Dethlefsen,C, Due,KM, Overvad,K] Department of Cardiology, Center for Cardiovascular Research, Aalborg Hospital, Aarhus University Hospital, Aalborg. [Jakobsen,MU, Overvad,K] Department of Epidemiology, School of Public Health, Aarhus University, Aarhus, Denmark. [Slimani,N, Chajès,V, Romieu,I] Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France. [May,AM, Peeter,PHM] Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht. [May,AM, van der A,DL, Bueno-de-Mesquita,HB] National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. [Sørensen,TIA] Institute of Preventive Medicine, Copenhagen University Hospital. [Halkjær,J, Tjønneland,A] The Danish Cancer Society, Institute of Cancer Epidemiology, Copenhagen, Denmark. [Clavel-Chapelon,F, Boutron-Ruault,M, Fagherazzi,G] Inserm, Centre for Research in Epidemiology and Population Health, Institut Gustave Roussy. Paris South University, Villejuif, France. [Teucher,B, Kaaks,R] German Cancer Research Center, Department of Cancer Epidemiology, Heidelberg. [Boeing,H, Schütze,M, Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Nuthetal, Germany. [Trichopoulou,A, Zylis,D] WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School. [Trichopoulou,A, Zylis,D, Makrygiannis,G] Hellenic Health Foundation, Athens, Greece. [Palli,D] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute, ISPO, Florence. [Mattiello,A] Department of Clinical and Experimental Medicine, Federico II University, Naples. [Tagliabue,G] Cancer Registry and Environmental Epidemiology Division, National Cancer Institute, Milan, Italy. [Bueno-de-Mesquita,HB] Department of Gastroenterology and Hepatology, University Medical Centre Utrecht (UMCU), Utrecht, The Netherlands. [Rodríguez,L] Public Health and Participation Directorate, Health and Health Care Services Council, Asturias. [Travier,N] Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology, IDIBELL, Barcelona. [Molina-Montes,E] Andalusian School of Public Health, Granada. [Molina-Montes,E, Huerta,JM, Barricarte,A, Amiano,P] CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona. [Huerta,JM] Department of Epidemiology, Murcia Regional Health Council, Murcia. [Barricarte,A] Public Health Institute of Navarra, Pamplona. [Amiano,P] Public Health Division of Gipuzkoa, Basque Government, Spain. [Manjer,J] Department of Surgery, Skåne University Hospital Malmö, Lund University. [Wirfält,E] Department of Clinical Sciences in Malmö/Nutrition Epidemiology, Lund University, Malmö. [Johansson,I] Department of Odontology, Umeå University. [Hallmans,G] Department of Public Health and Clinical Medicine, Umeå University, Nutritional Research, Umeå, Sweden. [Khaw,K] Clinical Gerontology Unit, Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge. [Wareham, NJ] MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge. [Crowe,F] Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford. [Riboli,E, Peeters, PHM] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK., This work is part of the project Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating out of Home and Obesity (PANACEA), which is supported by the European Union in the framework of the Public Health Programmme (Contract 2005328). The work was further supported by the European Commission: Public Health and Consumer Protection Directorate 1993–2004, Research Directorate-General 2005, Ligue contre le Cancer, Société 3M, Mutuelle Générale de l’Education Nationale, Institut National de la Santé de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center, Federal Ministry of Education and Research (Germany), Danish Cancer Society (Denmark), ISCIII (RETICC RD06/0020) of the Spanish Ministry of Health, the participating regional governments and institutions (Spain), Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, The Wellcome Trust (UK), Greek Ministry of Health, Greek Ministry of Education, Hellenic Ministry of Health, Stavros Niarchos Foundation, and the Hellenic Health Foundation (Greece), Italian Association for Research on Cancer, National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports, Dutch Ministry of Health, Dutch Prevention Funds, LK Research Funds, Dutch Zorg Onderzoek Nederland (ZON), World Cancer Research Fund (WCRF) (The Netherlands), and and Swedish Cancer Society, Swedish Scientific Council, Regional Government of Skane and Västerbotten (Sweden). This work is also part of the project Hepatic and Adipose Tissue and Functions in the Metabolic Syndrome (HEPADIP, www.hepadip.org), which is supported by the European Commission as an Integrated Project under the 6th Framework Programme (Contract LSHM-CT-2005-018734) and part of the research program of the Danish Obesity Research Centre (DanORC, www.danorc.dk), which is supported by the Danish Council for Strategic Research (Contract 2101-06-0005).
Subjects: Male, Health (social science), 030309 nutrition & dietetics, Obesidad, Ácidos grasos omega-3, Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], chemistry.chemical_compound, 0302 clinical medicine, Estudios prospectivos, Fosfolípidos, Modelos lineales, Prospective Studies, Masculino, Prospective cohort study, Phospholipids, chemistry.chemical_classification, 0303 health sciences, education.field_of_study, Weight change, Femenino, Middle Aged, n-3 fatty acids, Humanos, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Female, Original Article, lipids (amino acids, peptides, and proteins), Cohort study, Polyunsaturated fatty acid, medicine.medical_specialty, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], Population, Phospholipid, Check Tags::Male [Medical Subject Headings], 030209 endocrinology & metabolism, 03 medical and health sciences, Chemicals and Drugs::Lipids::Fats::Dietary Fats::Dietary Fats, Unsaturated::Fatty Acids, Omega-3 [Medical Subject Headings], Physiology (medical), Internal medicine, Fatty Acids, Omega-3, Omega-3 fatty acids, medicine, Humans, Obesity, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Models, Statistical::Linear Models [Medical Subject Headings], Chemicals and Drugs::Lipids::Phospholipids [Medical Subject Headings], education, Mediana edad, business.industry, Body Weight, Peso corporal, Body weight, Confidence interval, Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::Obesity [Medical Subject Headings], Endocrinology, Check Tags::Female [Medical Subject Headings], chemistry, Linear Models, Diseases::Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Body Weight [Medical Subject Headings], sense organs, business
Abstract: Journal Article; Research Support, Non-U.S. Gov't; OBJECTIVE We investigated the association between the proportion of long-chain n-3 polyunsaturated fatty acids (PUFA) in plasma phospholipids from blood samples drawn at enrollment and subsequent change in body weight. Sex, age, and BMI were considered as potential effect modifiers. METHOD A total of 1,998 women and men participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) were followed for a median of 4.9 years. The associations between the proportion of plasma phospholipid long-chain n-3 PUFA and change in weight were investigated using mixed-effect linear regression. RESULTS The proportion of long-chain n-3 PUFA was not associated with change in weight. Among all participants, the 1-year weight change was -0.7 g per 1% point higher long-chain n-3 PUFA level (95% confidence interval: -20.7 to 19.3). The results when stratified by sex, age, or BMI groups were not systematically different. CONCLUSION The results of this study suggest that the proportion of long-chain n-3 PUFA in plasma phospholipids is not associated with subsequent change in body weight within the range of exposure in the general population. Yes
Published: 2016

41. Genetic variability of the forkhead box O3 and prostate cancer risk in the European Prospective Investigation on Cancer

Author: Rudolf Kaaks, Eva Ardanaz, Heiner Boeing, María José Sánchez, Domenico Palli, Nicholas J. Wareham, Tina Karapetyan, Sabina Sieri, Mazda Jenab, Nina Roswall, Kim Overvad, Anne Tjønneland, Ruth C. Travis, Afshan Siddiq, José María Huerta, Anika Hüsing, Angelika Stein, H. Bas Bueno-de-Mesquita, Federico Canzian, Nerea Larrañaga, Mattias Johansson, Kay-Tee Khaw, Lucie Dostal, Jane Nautrup Østergaard, David Cox, Laudina Rodríguez, Daniele Campa, Rosario Tumino, Catalina Bonet, Per Lenner, Naomi E. Allen, Paolo Vineis, Dimosthenis Zylis, Dagmar Drogan, Antonia Trichopoulou, Department of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, German Institute of Human Nutrition Potsdam-Rehbrücke, German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Cancer Epidemiology Institute, Danish Cancer Society, Department of Cardiology, Aarhus University Hospital, Public Health and Participation Directorate, Health and Health Care Services Council, Catalan Institute of Oncology, Consorcio de Investigación Biomédica en Red especializado en Epidemiología y Salud Pública (CIBERESP), Los Centros de Investigación Biomédica en Red (CIBER), Granada Cancer Registry, Andalusian School of Public Health [Granada], Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), CIBER de Epidemiología y Salud Pública (CIBERESP), Murcia Regional Health Authority, Navarra Public Health Institute, Leyre 15, School of Clinical Medicine, University of Cambridge [UK] (CAM), Epidemiology Unit, Medical Research Council, Cancer Epidemiology Unit, University of Oxford [Oxford]-Cancer Epidemiology Unit, Department of Hygiene, Epidemiology and Medical Statistics, Molecular and Nutritional Epidemiology Unit, ISPO-Cancer Research and Prevention Institute, Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Cancer Registry, Civile - M.P.Arezzo Hospital, Centre for Environment and Health, Imperial College London-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU), Human Genetics Foundation (HuGeF), Università degli studi di Torino (UNITO), National Institute for Public Health and the Environment [Bilthoven] (RIVM), Department of Oncology and Radiation Sciences, Oncology, Umea University Hospital, Unit of Nutrition, Environment, and Cancer, Equipe 6, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Department of Epidemiology and Biostatistics, Imperial College London-Faculty of Medicine-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU)-Imperial College London-Faculty of Medicine-School of public health, Department of Epidemiology and Biostatistics, Department of Genomics of Common Disease, Division of Cancer Epidemiology, German Cancer Research Center, German Cancer Research Center (DKFZ), Aalborg Hospital-Aarhus University Hospital, Consorcio de Investigación Biomédica en Red especializado en Epidemiología y Salud Pública ( CIBERESP ), Andalusian School of Public Health, University of Cambridge [UK] ( CAM ), Azienda Ospedaliera 'Civile M.P.Arezzo', Human Genetics Foundation ( HuGeF ), Università degli studi di Torino ( UNITO ), National Institute for Public Health and the Environment [Bilthoven] ( RIVM ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Department of Epidemiology and Biostatistics, and Imperial College London-Faculty of Medicine-School of public health-Imperial College London-Faculty of Medicine-School of public health
Subjects: Oncology, Male, MESH: Signal Transduction, Cancer Research, MESH : Aged, MESH : Genotype, 030204 cardiovascular system & hematology, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Cohort Studies, MESH: Genotype, Prostate cancer, 0302 clinical medicine, Risk Factors, MESH: Risk Factors, genetic variability, MESH: Cohort Studies, media_common, MESH: Aged, 0303 health sciences, education.field_of_study, MESH: Middle Aged, MESH: Polymorphism, Single Nucleotide, MESH : Polymorphism, Single Nucleotide, Forkhead Box Protein O3, Longevity, MESH: Genetic Predisposition to Disease, Forkhead Transcription Factors, General Medicine, MESH: European Continental Ancestry Group, MESH : Adult, Middle Aged, prostate cancer, MESH : Risk Factors, MESH: Case-Control Studies, 3. Good health, European Prospective Investigation into Cancer and Nutrition, forkhead box, MESH : Forkhead Transcription Factors, Europe, FOXO3, MESH : Prostatic Neoplasms, Signal Transduction, Adult, medicine.medical_specialty, MESH : Case-Control Studies, Genotype, media_common.quotation_subject, MESH : Male, Population, MESH : Europe, MESH : Cohort Studies, Single-nucleotide polymorphism, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Polymorphism, Single Nucleotide, White People, MESH : European Continental Ancestry Group, 03 medical and health sciences, MESH: Forkhead Transcription Factors, Internal medicine, medicine, Humans, MESH : Middle Aged, Genetic Predisposition to Disease, education, 030304 developmental biology, Aged, MESH : Signal Transduction, MESH: Humans, MESH : Humans, Case-control study, Cancer, Prostatic Neoplasms, MESH: Adult, medicine.disease, MESH: Male, Case-Control Studies, MESH: Prostatic Neoplasms, MESH : Genetic Predisposition to Disease, MESH: Europe
Abstract: International audience; Forkhead box O3 (FOXO3) has a wide range of functions: it promotes tumor suppression, cell cycle arrest, repair of damaged DNA, detoxification of reactive oxygen species, apoptosis and plays a pivotal role in promoting longevity. FOXO3 is a key downstream target of the PI3K-Akt pathway in response to cellular stimulation by growth factors or insulin and has been proposed as a bridge between ageing and tumor suppression. Three SNPs in the FOXO3 gene (rs3800231, rs9400239 and rs479744) that have been shown to be strongly and consistently associated with longevity, were examined in relation to PC risk in a case control study of 1571 incident PC cases and 1840 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). There was no statistically significant association between the SNPs and PC risk regardless of the model of inheritance (dominant, codominant and recessive). The associations were not modified by disease aggressiveness, circulating levels of steroid sex hormones, or IGFs or BMI. We conclude that polymorphisms in the FOXO3 gene that are associated with longevity are not major risk factors for PC risk, in this population of Caucasian men.
Published: 2016

42. The INSIG2 rs7566605 polymorphism is not associated with body mass index and breast cancer risk

Author: Olga M. Sinilnikova, Rudolf Kaaks, Pilar Amiano, Anne Tjønneland, José Ramón Quirós, Eiliv Lund, Daniele Campa, Carla H. van Gils, Göran Hallmans, Kay-Tee Khaw, H. Bas Bueno-de-Mesquita, Anika Hüsing, Sabina Rinaldi, Nicholas J. Wareham, Nathalie Chabbert-Buffet, Kim Overvad, Eva Ardanaz, Sabine Rohrmann, Vittorio Krogh, Federico Canzian, Giovanna Masala, Françoise Clavel-Chapelon, María Dolores Chirlaque, Per Lenner, Carlotta Sacerdote, Esther Molina-Montes, Guy Fagherazzi, Jakob Stegger, James McKay, N. Charlotte Onland-Moret, Salvatore Panico, Rosario Tumino, Afshan Siddiq, Birgit Teucher, Timothy J. Key, Erifili Oustoglou, Ruth C. Travis, Veronique Chajes, Dimosthenis Zylis, Ulla Vogel, Antonia Trichopoulou, Elio Riboli, Nadia Slimani, Heiner Boeing, Núria Sala, Eva Fisher, Wareham, Nicholas [0000-0003-1422-2993], Khaw, Kay-Tee [0000-0002-8802-2903], Apollo - University of Cambridge Repository, Campa, D, Hüsing, A, Mckay, Jd, Sinilnikova, O, Vogel, U, Tjønneland, A, Overvad, K, Stegger, J, Clavel Chapelon, F, Chabbert Buffet, N, Fagherazzi, G, Trichopoulou, A, Zylis, D, Oustoglou, E, Rohrmann, S, Teucher, B, Fisher, E, Boeing, H, Masala, G, Krogh, V, Sacerdote, C, Panico, Salvatore, Tumino, R, Onland Moret, Nc, van Gils, Ch, Bueno de Mesquita, Hb, Lund, E, Chirlaque, Md, Sala, N, Quirós, Jr, Ardanaz, E, Amiano, P, Molina Montes, E, Hallmans, G, Lenner, P, Travis, Rc, Key, Tj, Wareham, N, Khaw, Kt, Rinaldi, S, Slimani, N, Chajes, V, Siddiq, A, Riboli, E, Kaaks, R, Canzian, F., and [Campa D, Hüssing A, Rohrmann S, Teucher B, Kaaks R, Canzian F] German Cancer Research Center (DKFZ), Heidelberg, Germany. [McKay JD, Slimani N, Chajes V] International Agency for Research on Cancer, Lyon, France. [Sinilnikova O] Hospices Civils de Lyon/Centre Léon Bérard, UMR5201 CNRS-Université Claude Bernard, Lyon, France. [Vogel U] National Food Institute Technical University of Denmark, Denmark. [Tjønneland A] Danish Cancer Society, Copenhagen, Denmark. [Overvad K] Aarhus University Hospital, Aalborg, Denmark. [Stegger J] Department of Cardiology, Cardiovascular Research Centre, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark. [Clavel-Chapelon F, Chabbert-Buffet N, Fagherazzi G] Institut Gustave Roussy, Villejuif, France. [Trichopoulou A, Zylis D] WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. [Trichopoulou A, Oustoglou E] Hellenic Health Foundation, Athens, Greece. [Fisher E, Boeing H] German Institute of Human Nutrition, Potsdam-Rehbruecke, Germany. [Masala G] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy. [Krogh V] Istituto Nazionale dei Tumori (IRCCS), Milan, Italy. [Sacerdote C] CPO Piemonte, Turin, Italy. [Panico S] Department of Clinical and Experimental Medicine Federico II University, Naples, Italy. [Tumino R] Azienda Ospedaliera 'Civile M.P.Arezzo' Ragusa, Italy. [Onland-Moret NC, van Gils CH] Julius Center, University Medical Center, Utrecht, The Netherlands. [Bueno-de-Mesquita HB] National Institute for Public Health and the Environment, Bilthoven, The Netherlands. [Lund E] Institute of Community Medicine University of Tromsø, Tromsø, Norway. [Chirlaque MD] Murcia Regional Health Council, Murcia, Spain. [Sala N] Catalan Institute of Oncology, Barcelona, Spain. [Quirós JR] Consejería de Salud y Servicios Sanitarios Principado de Asturias, Oviedo, Spain. [Ardanaz E] Public Health Institute of Navarra, Pamplona, Spain. [Amiano P] Public Health Department of Gipuzkoa, San Sebastian, Spain. [Molina-Montes E] Andalusian School of Public Health, Granada, Spain. [Chirlaque MD, Amiano P, Molina-Montes E] CIBER de Epidemiología y Salud Pública (CIBERESP), Spain. [Hallmans G, Lenner2 P] Umeå University, Umeå, Sweden. [Travis RC, Key TJ] Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK OX3 7LF. [Wareham N, Khaw KT] University of Cambridge, Cambridge, UK. [Siddiq A, Riboli E] Imperial College, London, UK.
Subjects: Oncology, Aging, Cancer Research, Genome-wide association study, 32 Biomedical and Clinical Sciences, Body Mass Index, Cohort Studies, Health Care::Environment and Public Health::Public Health::Epidemiologic Methods::Epidemiologic Research Design::Genome-Wide Association Study [Medical Subject Headings], 0302 clinical medicine, 2.1 Biological and endogenous factors, membrane protein, POPULATION, Cancer, 2. Zero hunger, 2 Aetiology, 0303 health sciences, education.field_of_study, Intracellular Signaling Peptides and Proteins, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 4203 Health Services and Systems, 3. Good health, Índice de masa muscular, INSIG2 protein, Adipose Tissue, Neoplasias de la mama, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intracellular Signaling Peptides and Proteins [Medical Subject Headings], Female, Life Sciences & Biomedicine, Cohort study, Research Article, Adult, Risk, medicine.medical_specialty, VDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk genetikk: 714, Genotype, Estudios de cohortes, Population, Polimorfismo Genético, COMMON GENETIC VARIANT, PHENOTYPES, 030209 endocrinology & metabolism, Single-nucleotide polymorphism, Breast Neoplasms, VDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Medical genetics: 714, lcsh:RC254-282, Estudio de Asociación del Genoma Completo, 03 medical and health sciences, Breast cancer, Health Care::Environment and Public Health::Public Health::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], SDG 3 - Good Health and Well-being, Clinical Research, Internal medicine, Breast Cancer, POLYGENIC CONTRIBUTION, medicine, Genetics, Humans, signal peptide, Neoplasm Invasiveness, Obesity, human, education, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], 030304 developmental biology, Nutrition, Aged, Science & Technology, Polymorphism, Genetic, Models, Genetic, business.industry, VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762, Prevention, Case-control study, 42 Health Sciences, Membrane Proteins, DNA, Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic [Medical Subject Headings], medicine.disease, 3211 Oncology and Carcinogenesis, Health Care::Environment and Public Health::Public Health::Epidemiologic Measurements::Biometry::Anthropometry::Body Mass Index [Medical Subject Headings], VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762, Case-Control Studies, Immunology, INSIG2 protein, human, business, Body mass index, Genome-Wide Association Study
Abstract: Background The single nucleotide polymorphism rs7566605, located in the promoter of the INSIG2 gene, has been the subject of a strong scientific effort aimed to elucidate its possible association with body mass index (BMI). The first report showing that rs7566605 could be associated with body fatness was a genome-wide association study (GWAS) which used BMI as the primary phenotype. Many follow-up studies sought to validate the association of rs7566605 with various markers of obesity, with several publications reporting inconsistent findings. BMI is considered to be one of the measures of choice to evaluate body fatness and there is evidence that body fatness is related with an increased risk of breast cancer (BC). Methods we tested in a large-scale association study (3,973 women, including 1,269 invasive BC cases and 2,194 controls), nested within the EPIC cohort, the involvement of rs7566605 as predictor of BMI and BC risk. Results and Conclusions In this study we were not able to find any statistically significant association between this SNP and BMI, nor did we find any significant association between the SNP and an increased risk of breast cancer overall and by subgroups of age, or menopausal status.
Published: 2016

43. Meat, fish, and colorectal cancer risk: the European Prospective Investigation into cancer and nutrition

Author: Salvatore Panico, Emmanuelle Kesse, Pietro Ferrari, Bertrand Hémon, Anne Tjønneland, Eiliv Lund, Guri Skeie, Timothy J. Key, Kim Overvad, Göran Berglund, H. Bas Bueno-de-Mesquita, Carmen Navarro, Mazda Jenab, Teresa Norat, Iréne Mattisson, Nicholas E. Day, Carlos González, Dagrun Engeset, María José Sánchez, Marie-Christine Boutron-Ruault, Rudolf Kaaks, Françoise Clavel, Mathieu Mazuir, Elio Riboli, Petra H.M. Peeters, Yannis Tountas, Göran Hallmans, Manuela M. Bergmann, Anja Olsen, Sheila Bingham, Nadia Slimani, Antonia Trichopoulou, Richard Palmqvist, Dimitrios Trichopoulos, Heiner Boeing, Rosario Tumino, Jakob Linseisen, Franco Berrino, Paolo Vineis, Rodolfo Saracci, J. Ramón Quirós, Eva Ardanaz, Kay-Tee Khaw, Domenico Palli, Alexandra Nieters, Unit of Nutrition, Environment, and Cancer, Catalan Institute of Oncology, Nutrition Unit, MRC Dunn Human, Department of Clinical Epidemiology, Aarhus University Hospital, Department of Cardiology and Department of Clinical Epidemiology, Institute of Cancer Epidemiology, Danish Cancer Society, Nutrition, hormones et cancer: épidémiologie et prévention (E3N), Epidémiologie, sciences sociales, santé publique (IFR 69), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke (DifE), Leibniz Association, Division of Clinical Epidemiology, Deutches Krebsforschungszentrum, Department of Hygiene and Epidemiology, University of Athens Medical School [Athens], Epidemiology Unit, Istituto Tumori, Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Center, Department of Clinical and Experimental Medicine, Università degli studi di Napoli Federico II, Ragusa Cancer Registry, Azienda Ospedaliera Civile MP, University of Torino and CPO-Piemonte, Università degli studi di Torino (UNITO), Center for Nutrition and Health, National Institute of Public Health and Environment, Julius Center for Health Sciences and Primary Care, VU University Medical Center [Amsterdam], Institute of Community Medicine, University of Tromsø (UiT), Public Health Institute of Navarra, Department of Epidemiology, Epidemiology Department, Health Council of Murcia, Public Health and Health Planning Directorate, Andalusian School of Public Health [Granada], Malmö Diet and Cancer Study, Lund University [Lund], Department of Nutritional Research, Umeå University, Department of Medical Biosciences, Pathology, Strangeways Research Laboratory, Clinical Gerontology Unit, University of Cambridge [UK] (CAM), Cancer Research UK Epidemiology Unit, University of Oxford [Oxford], The work described in this article was carried out with financial support of the 'Europe Against Cancer Program' of the European Commission (SANCO), the Danish Cancer Society, German Cancer Aid, Ligue Nationale contre le Cancer, the 3M Company, INSERM, the German Cancer Research Center, the GermanFederal Ministry of Education and Research, the Dutch Ministry of Public Health, Welfare and Sports, the National Cancer Registry and the Regional Cancer Registries Amsterdam, East and Maastricht of The Netherlands, the Norwegian Cancer Society, the Norwegian Research Council, the Health Research Fund (FIS) of the Spanish Ministry of Health, the Greek Ministry of Health, the Greek Ministry of Education, the Italian Association for Research on Cancer, Spanish Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, and ISCIII, Red de Centros RCESP, C03/09, the Swedish Cancer Society, the Swedish Scientific Council, the Regional Government of Skane, Sweden, Cancer Research UK, the Medical Research Council, U.K., the Stroke Association, U.K., the British Heart Foundation, the Department of Health, U.K., the Food Standards Agency, U.K., and the Wellcome Trust, U.K., University of Naples Federico II = Università degli studi di Napoli Federico II, Università degli studi di Torino = University of Turin (UNITO), University of Oxford, Clavel-Chapelon, F., Norat, T, Bingham, S, Ferrari, P, Slimani, N, Jenab, M, Mazuir, M, Overvad, K, Olsen, A, Tjonneland, A, Clavel, F, BOUTRON RUAULT, Mc, Kesse, E, Boeing, H, Bergmann, Mm, Nieters, A, Linseisen, J, Trichopoulou, A, Trichopoulos, D, Tountas, Y, Berrino, F, Palli, D, Panico, Salvatore, Tumino, R, Vineis, P, BUENO DE MESQUITA, Hb, Peeters, Ph, Engeset, D, Lund, E, Skeie, G, Ardanaz, E, Gonzalez, C, Navarro, C, Quiros, Jr, Sanchez, Mj, Berglund, G, Mattisson, I, Hallmans, G, Palmqvist, R, Day, Ne, Khaw, Kt, Key, Tj, SAN JOAQUIN, M, Hemon, B, Saracci, R, Kaaks, R, and Riboli, E.
Subjects: Dietary Fiber, Male, Cancer Research, 030309 nutrition & dietetics, Colorectal cancer, MESH: Food Habits, Gastroenterology, Poultry, MESH: Proportional Hazards Models, 0302 clinical medicine, Risk Factors, MESH: Poultry, Surveys and Questionnaires, Odds Ratio, MESH: Animals, Prospective Studies, Prospective cohort study, 2. Zero hunger, MESH: Aged, MESH: Meat, 0303 health sciences, MESH: Middle Aged, MESH: Risk, Fishes, Absolute risk reduction, MESH: Life Style, Confounding Factors, Epidemiologic, Middle Aged, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, Oncology, Research Design, 030220 oncology & carcinogenesis, Income, Red meat, Educational Status, Population study, Female, Colorectal Neoplasms, Adult, medicine.medical_specialty, Meat, [SDV.CAN]Life Sciences [q-bio]/Cancer, Risk Assessment, Article, MESH: Multivariate Analysis, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Animals, Humans, ddc:610, European Union, Risk factor, Life Style, Aged, Proportional Hazards Models, MESH: Humans, business.industry, MESH: Questionnaires, Cancer, MESH: Adult, Feeding Behavior, medicine.disease, MESH: Male, MESH: Odds Ratio, MESH: Prospective Studies, Surgery, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, MESH: Fishes, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Multivariate Analysis, MESH: Dietary Fiber, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Europe, business, MESH: Female, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, MESH: Colorectal Neoplasms
Abstract: Background: Current evidence suggests that high red meat intake is associated with increased colorectal cancer risk. High fish intake may be associated with a decreased risk, but the existing evidence is less convincing. Methods: We prospectively followed 478 040 men and women from 10 European countries who were free of cancer at enrollment between 1992 and 1998. Information on diet and lifestyle was collected at baseline. After a mean follow-up of 4.8 years, 1329 incident colorectal cancers were documented. We examined the relationship between intakes of red and processed meat, poultry, and fish and colorectal cancer risk using a proportional hazards model adjusted for age, sex, energy (nonfat and fat sources), height, weight, work-related physical activity, smoking status, dietary fiber and folate, and alcohol consumption, stratified by center. A calibration substudy based on 36 994 subjects was used to correct hazard ratios (HRs) and 95% confidence intervals (CIs) for diet measurement errors. All statistical tests were two-sided. Results: Colorectal cancer risk was positively associated with intake of red and processed meat (highest [>160 g/day] versus lowest [80 g/day versus
Published: 2016

44. Diet quality scores and prediction of all-cause, cardiovascular and cancer mortality in a pan-european cohort study

Author: Lassale, Camille, Gunter, Marc J., Romaguera, Dora, Peelen, Linda M., Van der Schouw, Yvonne T., Beulens, Joline W. J., Freisling, Heinz, Muller, David C., Ferrari, Pietro, Huybrechts, Inge, Fagherazzi, Guy, Boutron-Ruault, Marie-Christine, Affret, Aurelie, Overvad, Kim, Dahm, Christina C., Olsen, Anja, Roswall, Nina, Tsilidis, Konstantinos K., Katzke, Verena A., Kuehn, Tilman, Buijsse, Brian, Quiros, Jose-Ramon, Sanchez-Cantalejo, Emilio, Etxezarreta, Nerea, Maria Huerta, Jose, Barricarte, Aurelio, Bonet, Catalina, Khaw, Kay-Tee, Key, Timothy J., Trichopoulou, Antonia, Bamia, Christina, Lagiou, Pagona, Palli, Domenico, Agnoli, Claudia, Tumino, Rosario, Fasanelli, Francesca, Panico, Salvatore, Bueno-de-Mesquita, H. Bas, Boer, Jolanda M. A., Sonestedt, Emily, Nilsson, Lena Maria, Renstrom, Frida, Weiderpass, Elisabete, Skeie, Guri, Lund, Eiliv, Moons, Karel G. M., Riboli, Elio, Tzoulaki, Ioanna, Khaw, Kay-Tee [0000-0002-8802-2903], Apollo - University of Cambridge Repository, Epidemiology and Data Science, EMGO - Lifestyle, overweight and diabetes, Lassale, Camille, Gunter, Marc J, Romaguera, Dora, Peelen, Linda M, Van der Schouw, Yvonne T, Beulens, Joline W. J, Freisling, Heinz, Muller, David C, Ferrari, Pietro, Huybrechts, Inge, Fagherazzi, Guy, Boutron Ruault, Marie Christine, Affret, Aurélie, Overvad, Kim, Dahm, Christina C, Olsen, Anja, Roswall, Nina, Tsilidis, Konstantinos K, Katzke, Verena A, Kühn, Tilman, Buijsse, Brian, Quirós, José Ramón, Sánchez Cantalejo, Emilio, Etxezarreta, Nerea, Huerta, José María, Barricarte, Aurelio, Bonet, Catalina, Khaw, Kay Tee, Key, Timothy J, Trichopoulou, Antonia, Bamia, Christina, Lagiou, Pagona, Palli, Domenico, Agnoli, Claudia, Tumino, Rosario, Fasanelli, Francesca, Panico, Salvatore, Bueno de Mesquita, H. Ba, Boer, Jolanda M. A, Sonestedt, Emily, Nilsson, Lena Maria, Renström, Frida, Weiderpass, Elisabete, Skeie, Guri, Lund, Eiliv, Moons, Karel G. M, Riboli, Elio, Tzoulaki, Ioanna, [Lassale,C, Gunter,MJ, Romaguera,D, Tsilidis,KK, Riboli,E, Tzoulaki,I] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, United Kingdom. [Romaguera,D] Instituto de Investigación Sanitaria de Palma (IdISPa), Palma de Mallorca, Spain. [Romaguera,D, Quirós,J, Sánchez-Cantalejo,E, Etxezarreta,N, Huerta,JM, Barricarte,A, Bonet,C] CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain. [Peelen,LM, Schouw,ITV, Beulens,JWJ, Moons,KGM] Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands.[Freisling,H, Muller,DC, Ferrari,P, Huybrechts,I] International Agency for Research on Cancer, Lyon, France. [Fagherazz,G, Boutron-Ruault,M, Affret,A] Institut National de la Santé et de la Recherche Médicale, Center for Research in Epidemiology and Population, Health, Villejuif, France. Institut Gustave Roussy, Villejuif, France. Paris South University, Unité Mixte de Recherche, Villejuif, France. [Overvad,K, Dahm,CC] Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark. [Olsen,A, Roswall,N] Danish Cancer Society, Institute of Cancer Epidemiology, Copenhagen, Denmark. [Tsilidis,KK] German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Heidelberg, Germany. [Katzke,VA, Kühn,T] Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke German Institute of Human Nutrition, Potsdam, Germany. [Buijsse,B] Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece. [Quirós,R] Public Health Directorate, Asturias, Oviedo, Spain. [Sánchez-Cantalejo,E] Andalusian School of Public Health, Granada, Spain. [Etxezarreta,N] Public Health Direction and Biodonostia Basque Regional Health Department, San Sebastian, Spain. [Huerta,JM] Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain. [Barricarte,A] Navarre Public Health Institute, Pamplona, Spain. [Bonet,C] Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology, Barcelona, Spain. [Khaw,K] University of Cambridge School of Clinical Medicine, Clinical Gerontology Unit, Cambridge, United Kingdom. [Key,J] Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, United Kingdom. [Trichopoulou,A, Bamia,C, Lagiou,P] Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. Hellenic Health Foundation, Athens, Greece. [Palli,D] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute—ISPO, Florence, Italy. [Agnoli,C] Epidemiology and Prevention Unit, Department of Preventive and Predictive Medicine, Foundation of the Carlo Besta Neurological Institute, Milan, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, 'Civic MP Arezzo' Hospital, Ragusa, Italy. [Fasanelli,F] Human Genetics Foundation, Turin, Italy. [Bueno-de-Mesquita,HB, Boer,JMA] Center for Nutrition, Prevention and Health Services, National Institute for Public Health and the Environment, Bilthoven, Netherlands. [Sonestedt,E] Department of Clinical Sciences in Malmö, Lund University, Lund, Sweden. [Nilsson,LM, Renström,F] Department of Public Health and Clinical Medicine, Nutritional Research, Umeå University, Umeå, Sweden. [Weiderpass,E, Skeie,G, Lund,E] Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway. [Weiderpass,E] Department of Research, Cancer Registry of Norway, Oslo, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland., Funding: The coordination of EPIC is financially supported by the European Commission (DGSANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), Health Research Fund (FIS), PI13/00061 to Granada, Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RETIC (RD06/0020) (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), Cancer Research UK (14136 to EPIC-Norfolk, and C570/ A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/ M012190/1 to EPIC-Oxford) (United Kingdom).
Subjects: Male, humanos, Phenomena and Processes::Physiological Phenomena::Body Constitution::Body Weights and Measures::Body Mass Index [Medical Subject Headings], Social Sciences, Índice de masa corporal, Global Health, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Cohort Studies, distribución por sexos, Mathematical and Statistical Techniques, Sociology, Risk Factors, Neoplasms, Medicine and Health Sciences, Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Musculoskeletal Physiological Phenomena::Musculoskeletal Physiological Processes::Movement::Motor Activity [Medical Subject Headings], Public and Occupational Health, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Nutritional Status [Medical Subject Headings], Estado Nutricional, estudios de cohortes, mediana edad, Factores de Riesgo, neoplasias, Medicine(all), Nutrition and Dietetics, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, Agricultural and Biological Sciences(all), dieta, Agriculture, Public Health, Global Health, Social Medicine and Epidemiology, Estudios Prospectivos, Plants, Diseases::Neoplasms [Medical Subject Headings], Middle Aged, Neoplasias, Näringslära, Cardiovascular Diseases, Hábitos alimenticios, estilo de vida, Physical Sciences, Medicine, Dieta, Female, Statistics (Mathematics), Research Article, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], General Science & Technology, Science, Estudios de cohortes, European Continental Ancestry Group, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Habits::Smoking [Medical Subject Headings], enfermedades cardiovasculares, Crops, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings], Research and Analysis Methods, White People, Education, Fruits, Age Distribution, distribución por edades, SDG 3 - Good Health and Well-being, MD Multidisciplinary, Anatomy::Cardiovascular System [Medical Subject Headings], Journal Article, factores de riesgo, Humans, Statistical Methods, Sex Distribution, Life Style, Educational Attainment, Nutrition, Sistema cardiovascular, Biochemistry, Genetics and Molecular Biology(all), Organisms, Biology and Life Sciences, Physical Activity, Nutrients, Actividad motora, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Feeding Behavior::Food Habits [Medical Subject Headings], Diet, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Hábito de Fumar, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, grupo de ascendencia continental europea, Mathematics, Forecasting, Crop Science
Abstract: Scores of overall diet quality have received increasing attention in relation to disease aetiology; however, their value in risk prediction has been little examined. The objective was to assess and compare the association and predictive performance of 10 diet quality scores on 10-year risk of all-cause, CVD and cancer mortality in 451,256 healthy participants to the European Prospective Investigation into Cancer and Nutrition, followed-up for a median of 12.8y. All dietary scores studied showed significant inverse associations with all outcomes. The range of HRs (95% CI) in the top vs. lowest quartile of dietary scores in a composite model including non-invasive factors (age, sex, smoking, body mass index, education, physical activity and study centre) was 0.75 (0.72-0.79) to 0.88 (0.84-0.92) for all-cause, 0.76 (0.69-0.83) to 0.84 (0.76-0.92) for CVD and 0.78 (0.73-0.83) to 0.91 (0.85-0.97) for cancer mortality. Models with dietary scores alone showed low discrimination, but composite models also including age, sex and other non-invasive factors showed good discrimination and calibration, which varied little between different diet scores examined. Mean C-statistic of full models was 0.73, 0.80 and 0.71 for all-cause, CVD and cancer mortality. Dietary scores have poor predictive performance for 10-year mortality risk when used in isolation but display good predictive ability in combination with other non-invasive common risk factors., The coordination of EPIC is financially supported by the European Commission (D-GSANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC- Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS), PI13/00061 to Granada, Regional Governments of Andalucia, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skane and Vasterbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom).
Published: 2016

45. Modifiable causes of premature death in middle-age in Western Europe : Results from the EPIC cohort study

Author: Marc J. Gunter, Ellen A. Struijk, Paul Brennan, Paolo Vineis, Christina Bamia, Guri Skeie, David C. Muller, M. Luisa Redondo, Cornelia Weikert, Salvatore Panico, Elena Molina-Portillo, Antonio Agudo, Rosario Tumino, Françoise Clavel, W M Monique Verschuren, Petra H.M. Peeters, Olle Melander, Jone M. Altzibar, Heiner Boeing, H. Bas Bueno-de-Mesquita, Ruth C. Travis, Elisabete Weiderpass, Gunnar Engström, Malin Sund, Teresa Norat, Anne Tjønneland, Manuela M. Bergmann, Philippos Orfanos, Laureen Dartois, Nicholas J. Wareham, Mattias Johansson, Elio Riboli, Kuanrong Li, Kay-Tee Khaw, Neil Murphy, Eiliv Lund, Antonia Trichopoulou, Marie-Christine Boutron-Ruault, Domenico Palli, Rudolf Kaaks, Konstantinos K. Tsilidis, Lluís Cirera, Pietro Ferrari, Valeria Pala, Timothy J. Key, Kim Overvad, Eva Ardanaz, Muller, David C, Murphy, Neil, Johansson, Mattia, Ferrari, Pietro, Tsilidis, Konstantinos K, Boutron Ruault, Marie Christine, Clavel, Francoise, Dartois, Laureen, Li, Kuanrong, Kaaks, Rudolf, Weikert, Cornelia, Bergmann, Manuela, Boeing, Heiner, Tjønneland, Anne, Overvad, Kim, Redondo, M. Luisa, Agudo, Antonio, Molina Portillo, Elena, Altzibar, Jone M, Cirera, Lluí, Ardanaz, Eva, Khaw, Kay Tee, Wareham, Nicholas J, Key, Timothy J, Travis, Ruth C, Bamia, Christina, Orfanos, Philippo, Trichopoulou, Antonia, Palli, Domenico, Pala, Valeria, Tumino, Rosario, Vineis, Paolo, Panico, Salvatore, Bueno de Mesquita, H. Ba, Verschuren, W. M. Monique, Struijk, Ellen A, Peeters, Petra H, Engström, Gunnar, Melander, Olle, Sund, Malin, Weiderpass, Elisabete, Skeie, Guri, Lund, Eiliv, Norat, Teresa, Gunter, Marc, Riboli, Elio, Brennan, Paul, [Muller,DC, Johansson,M, Ferrari,P, Brennan,P] International Agency for Research on Cancer, Lyon, France. [Murphy,N, Vineis,P, Bueno-de-Mesquita,HB, Peeters,PH, Norat,T, Gunter,M, Riboli,E] School of Public Health, Imperial College London, London, UK] [Tsilidis,KK] Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece. Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Boutron-Ruault,M] Centre for Research in Epidemiology and Population Health (CESP), Villejuif, France. [Boutron-Ruault,M, Clavel,F, Dartois,L] Université Paris Sud, Villejuif, France. [Boutron-Ruault,M, Dartois,L, Dartois,L] Inserm, Centre for Research in Epidemiology and Population Health (CESP), Villejuif, France. [Li,K, Kaaks,R] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Weikert,C, Bergmann,M, Boeing,H] German Institute of Human Nutrition Potsdam-Rehbrücke (DifE), Nuthetal, Germany. [Tjønneland,A] Danish Cancer Society Research Center, Copenhagen, Denmark. [Overvad,K] Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark. [Redondo,ML] Public Health Directorate, Asturias, Spain. [Agudo,A] Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology, Barcelona, Spain. [Molina-Portillo,E] Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain. [Molina-Portillo,E, Altzibar,JM, Cirera,M, Ardanaz,E] Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiología y Salud Pública-CIBERESP), Madrid, Spain. [Altzibar,JM] Public Health Division of Gipuzkoa-BIODONOSTIA, Basque Regional Health Department, Donostia - San Sebastián, Spain. [Cirera, L] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. Department of Health and Social Sciences, Universidad de Murcia, Murcia, Spain. Department of Health and Social Sciences, Universidad de Murcia, Murcia, Spain. [Ardanaz,E] Navarra Public Health Institute, Pamplona, Spain. Navarra Institute for Health Research (IdiSNA) Pamplona, Pamplona, Spain. [Khaw,K] School of Clinical Medicine, University of Cambridge, Cambridge, UK. [Wareham,NJ] MRC Epidemiology Unit, University of Cambridge, Cambridge, UK. [Key,TJ, Travis,RC] Cancer Epidemiology Unit, University of Oxford, Oxford, UK. [Bamia,C, Orfanos,P, Trichopoulou,A] Hellenic Health Foundation, Athens, Greece. Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. [Palli,D] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy. [Pala,V] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, 'Civic - M. P. Arezzo' Hospital, ASP Ragusa, Ragusa, Italy. [Vineis,P] Human Genetics Foundation (HuGeF), Torino, Italy. [Panico,S] Dipartimento di Medicina Clinica e Sperimentale, Federico II University, Naples, Italy. [Bueno-de-Mesquita,HB, Verschuren,WMM] Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. [Bueno-de-Mesquita,HB] Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands. Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. [Verschuren,WMM, Struijk,EA, Peeters,PH] Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. [Engström,G] Department of Clinical Science, Malmö Lund University, Lund, Sweden. [Melander,O] Department of Clinical Sciences, Hypertension & Cardiovascular Disease, Clinical Research Centre, Malmö University Hospital, Malmö, Sweden. [Sund,M] Department of Surgical and Perioperative Sciences, Umea University, Umea, Sweden. [Weiderpass,E, Skeie,G, Lund,E] Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway. [Weiderpass,E] Department of Research, Cancer Registry of Norway, Oslo, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Samfundet Folkhälsan, Helsinki, Finland. [Skeie,G, Lund,E] The Arctic University of Norway, Tromsø, Norway., This work was supported by the French Social Affairs & Health Ministry, Department of Health (Direction Générale de la Santé). The work undertaken by David C Muller for this project was performed during the tenure of an IARC-Australia fellowship supported by Cancer Council Australia. Elio Riboli was supported by the Imperial College Biomedical Research Centre funded by the National Institute of Health Research of UK. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), Nordic Centre of xcellence programme on Food, Nutrition and Health. (Norway), Health Research Fund (FIS), PI13/00061 to Granada, Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RETIC (RD06/0020) (Spain), Swedish Cancer Society, Swedish Scientific Council and County Councils of Skåne and Västerbotten (Sweden), Cancer Research UK (14136 to EPIC-Norfolk, C570/A16491 to EPIC-Oxford),Medical Research Council (1000143 to EPIC-Norfolk) (United Kingdom). The sponsors did not have any input into study design, study conduct, data collection, analysis, or interpretation nor did they influence the preparation, review, or approval of the manuscript., Khaw, Kay-Tee [0000-0002-8802-2903], Wareham, Nicholas [0000-0003-1422-2993], and Apollo - University of Cambridge Repository
Subjects: Gerontology, Male, 030204 cardiovascular system & hematology, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Cohort Studies, Institut Gustave Roussy, 0302 clinical medicine, Risk Factors, Medicine, 030212 general & internal medicine, Prospective Studies, Diseases::Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Body Weight::Overweight [Medical Subject Headings], Non-U.S. Gov't, media_common, Medicine(all), VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Vital Statistics::Mortality::Mortality, Premature [Medical Subject Headings], Research Support, Non-U.S. Gov't, Smoking, Public Health, Global Health, Social Medicine and Epidemiology, 11 Medical And Health Sciences, General Medicine, Middle Aged, Europe, Hypertension, Absolute risk, Modifiable risk factors, Mortality, Premature death, Attributable fraction, language, Female, Cohort study, Research Article, Adult, medicine.medical_specialty, Alcohol Drinking, media_common.quotation_subject, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Habits::Smoking [Medical Subject Headings], Library science, Motor Activity, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings], Research Support, Danish, 03 medical and health sciences, Diseases::Cardiovascular Diseases::Vascular Diseases::Hypertension [Medical Subject Headings], Life Expectancy, Excellence, General & Internal Medicine, Journal Article, Humans, Obesity, Aged, business.industry, Mortality, Premature, Public health, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Vital Statistics::Life Expectancy [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Physical Examination::Body Constitution::Body Weights and Measures::Waist-Hip Ratio [Medical Subject Headings], language.human_language, Cancer registry, Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::Obesity [Medical Subject Headings], Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Mortalidad, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Drinking Behavior::Alcohol Drinking [Medical Subject Headings], Life expectancy, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business, Welfare, Modifiable risk factor, Mortalidad prematura
Abstract: Background: Life expectancy is increasing in Europe, yet a substantial proportion of adults still die prematurely before the age of 70 years. We sought to estimate the joint and relative contributions of tobacco smoking, hypertension, obesity, physical inactivity, alcohol and poor diet towards risk of premature death. Methods: We analysed data from 264,906 European adults from the EPIC prospective cohort study, aged between 40 and 70 years at the time of recruitment. Flexible parametric survival models were used to model risk of death conditional on risk factors, and survival functions and attributable fractions (AF) for deaths prior to age 70 years were calculated based on the fitted models. Results: We identified 11,930 deaths which occurred before the age of 70. The AF for premature mortality for smoking was 31 % (95 % confidence interval (CI), 31–32 %) and 14 % (95 % CI, 12–16 %) for poor diet. Important contributions were also observed for overweight and obesity measured by waist-hip ratio (10 %; 95 % CI, 8–12 %) and high blood pressure (9 %; 95 % CI, 7–11 %). AFs for physical inactivity and excessive alcohol intake were 7 % and 4 %, respectively. Collectively, the AF for all six risk factors was 57 % (95 % CI, 55–59 %), being 35 % (95 % CI, 32–37 %) among never smokers and 74 % (95 % CI, 73–75 %) among current smokers. Conclusions: While smoking remains the predominant risk factor for premature death in Europe, poor diet, overweight and obesity, hypertension, physical inactivity, and excessive alcohol consumption also contribute substantially. Any attempt to minimise premature deaths will ultimately require all six factors to be addressed., This work was supported by the French Social Affairs & Health Ministry, Department of Health (Direction Générale de la Santé). The work undertaken by David C Muller for this project was performed during the tenure of an IARC-Australia fellowship supported by Cancer Council Australia. Elio Riboli was supported by the Imperial College Biomedical Research Centre funded by the National Institute of Health Research of UK. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Nordic Centre of Excellence programme on Food, Nutrition and Health. (Norway); Health Research Fund (FIS), PI13/00061 to Granada, Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Scientific Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk) (United Kingdom). The sponsors did not have any input into study design, study conduct, data collection, analysis, or interpretation nor did they influence the preparation, review, or approval of the manuscript.
Published: 2016

46. Combined genetic and splicing analysis of BRCA1 c.[594-2A > C; 641A > G] highlights the relevance of naturally occurring in-frame transcripts for developing disease gene variant classification algorithms

Author: Barbara Wappenschmidt, Fergus J. Couch, Norbert Arnold, Claude Houdayer, Manjeet K. Bolla, Omar Soukarieh, Sean V. Tavtigian, Irene L. Andrulis, Alexandra Becker, Alexandra Martins, Qin Wang, Sara Margolin, Paolo Radice, Janet E. Olson, Mitul Shah, Juul T. Wijnen, Amanda B. Spurdle, Nichola Johnson, Carole Brewer, Harald Surowy, Graham G. Giles, Ana Blanco, Kamila Czene, Thomas Hansen, Wendy S. Rubinstein, Anja Rudolph, Christian F. Singer, Antonis C. Antoniou, Douglas F. Easton, Fiona M. Blows, Michael T. Parsons, kConFab Investigators, Annika Lindblom, Nicola K. Poplawski, Melissa C. Southey, Emily Hallberg, Vanessa Lattimore, Yvette van Ierland, Logan C. Walker, Joe Dennis, Gord Glendon, Ana Vega, Diether Niederacher, Laurent Castera, David E. Goldgar, Ulrike Faust, Roger L. Milne, Marta Santamariña, Lesley McGuffog, Jan Hauke, Christi J. van Asperen, Michela Raponi, Irene López-Perolio, Diana Baralle, Tina Pesaran, Huong Meeks, Peter J. Hulick, Miguel de la Hoya, Philip Whiley, Raquel Behar, Jenny Chang-Claude, Elizabeth C. Chao, Henrik Flyger, Doris Steinemann, Pham Phuong Mai, Stig E. Bojesen, Maaike P.G. Vreeswijk, Sandrine M. Caputo, Jan Sullivan, Julian Peto, Barbara Burwinkel, Laura Galastri, Per Hall, Kyriaki Michailidou, Bernd Dworniczak, Molecular Oncology Laboratory, Hospital Clínico San Carlos, Génétique du cancer et des maladies neuropsychiatriques (GMFC), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Instituto de Investigación Sanitaria del Hospital Clínico San Carlos [Madrid, Spain] (IdISSC), Fundación Pública Galega Medicina Xenómica-SERGAS & Grupo de Medicina Xenómica--USC, CIBER de Enfermedades Raras (CIBERER), Division of Genetics and Population Health, Queensland Institute of Medical Research, Genetics, University of Southampton, University of Otago [Dunedin, Nouvelle-Zélande], Department of Clinical Genetics and GROM, School for Oncology and Developmental Biology, Human Genetics Division [Southampton], Division of Molecular Gyneco-Oncology, Department of Gynaecology and Obstetrics, Institut Laue-Langevin (ILL), University of Melbourne, Division of Oncology, Department of Gynaecology and Obstetrics, University Hospital Schleswig–Holstein, Institute of Cell and Molecular Pathology, Medizinische Hochschule Hannover (MHH), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), DIEP/DSV (DIEP/DSV), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Ambry Genetics [Aliso Viejo, CA, USA], Department of Clinical Genetics, Royal Devon & Exeter Hospital, Department of Pathology, The University of Melbourne, Melbourne, Victoria, Australia, Leiden University Medical Center (LUMC), Universiteit Leiden-Universiteit Leiden, Division of Special Gynecology, Medizinische Universität Wien = Medical University of Vienna-Department of OB/GYN, Metabolic Unit, Dept Clinical Chemistry, Division of Cancer Epidemiology and Genetics, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Non-Communicable Disease Epidemiology Unit, London School of Hygiene and Tropical Medicine (LSHTM), Molecular Epidemiology Research Group, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department of Breast Surgery, Herlev and Gentofte Hospital, Karolinska University Hospital [Stockholm], Division of Cancer Epidemiology, Unit of Genetic Susceptibility to Cancer, Department of Experimental Oncology and Molecular Medici, Cancer Epidemiology Centre, Cancer Council Victoria, Departments of Molecular Genetics and Laboratory Medicine and Pathobiology, University of Toronto-Cancer Care Ontario, Ontario Cancer Genetics Network, Cancer Care Ontario, Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], University of Science and Technology Beijing [Beijing] (USTB), Strangeways Research Laboratory, University of Cambridge [UK] (CAM)-Department of Public Health and Primary Care-Centre for Cancer Genetic Epidemiology, Cancer Research U.K. Genetic Epidemiology Unit, Department of Laboratory Medicine and Pathology, Mayo Clinic, Department of Oncological Sciences, University of Utah-Huntsman Cancer Institute, Center for Human and Clinical Genetics, Université de Pau et des Pays de l'Adour (UPPA), International Agency for Cancer Research (IACR), ILL, Service de Biochimie et de Biologie Moléculaire [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Wang, Jean [0000-0002-9139-0627], Dennis, Joe [0000-0003-4591-1214], Antoniou, Antonis [0000-0001-9223-3116], Easton, Douglas [0000-0003-2444-3247], Apollo - University of Cambridge Repository, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: 0301 basic medicine, Adult, RNA Splicing, [SDV]Life Sciences [q-bio], DNA Mutational Analysis, Breast Neoplasms, Biology, 03 medical and health sciences, Exon, Genetics, Humans, Allele, Molecular Biology, Gene, Genetics (clinical), ComputingMilieux_MISCELLANEOUS, Aged, Ovarian Neoplasms, Messenger RNA, BRCA1 Protein, Tumor Suppressor Proteins, Alternative splicing, RNA, General Medicine, Articles, Exons, Middle Aged, Splicing regulatory element, 3. Good health, Gene Expression Regulation, Neoplastic, Alternative Splicing, 030104 developmental biology, RNA splicing, Mutation, Female, RNA Splice Sites
Abstract: A recent analysis using family history weighting and co-observation classification modeling indicated that BRCA1 c.594-2A>C (IVS9-2A>C), previously described to cause exon 10 skipping (a truncating alteration), displays characteristics inconsistent with those of a high risk pathogenic BRCA1 variant. We used large-scale genetic and clinical resources from the ENIGMA, CIMBA and BCAC consortia to assess pathogenicity of c.594-2A>C. The combined odds for causality considering case-control, segregation, and breast tumor pathology information was 3.23x10-8. Our data indicate that c.594-2A>C is always in cis with c.641A>G.The spliceogenic effect of c.[594-2A>C;641A>G] was characterized using RNA analysis of human samples and splicing minigenes. As expected, c.[594-2A>C; 641A>G] caused exon 10 skipping, albeit not due to c.594-2A>C impairing the acceptor site but rather by c.641A>G modifying exon 10 splicing regulatory element(s). Multiple blood-based RNA assays indicated that the variant allele did not produce detectable levels of full-length transcripts, with a per allele BRCA1 expression profile comprised of ?70-80% truncating transcripts, and ?20-30% of in-frame ?9,10 transcripts predicted to encode a BRCA1 protein with tumor suppression function.We confirm that BRCA1c.[594-2A>C;641A>G] should not be considered a high-risk pathogenic variant. Importantly, results from our detailed mRNA analysis suggest that BRCA-associated cancer risk is likely not markedly increased for individuals who carry a truncating variant in BRCA1 exons 9 or 10, or any other BRCA1 allele that permits 20-30% of tumor suppressor function. More generally, our findings highlight the importance of assessing naturally occurring alternative splicing for clinical evaluation of variants in disease-causing genes.
Published: 2016

47. Clinical Characteristics and Risk Factors of Extensive Macular Atrophy with Pseudodrusen: The EMAP Case-Control National Clinical Trial

Author: Douillard, Aymeric, Picot, Marie-Christine, Delcourt, Cecile, Lacroux, Annie, Zanlonghi, Xavier, Puech, Bernard, Defoort-Dhelemmes, Sabine, Drumare, Isabelle, Jozefowicz, Elsa, Bocquet, Beatrice, Baudoin, Corinne, Marzouka, Nour Al-Dain, Perez-Roustit, Sarah, Arsene, Sophie, Gissot, Valerie, Devin, Francois, Arndt, Carl, Wolff, Benjamin, Mauget-Faysse, Martine, Quaranta, Maddalena, Mura, Thibault, Deplanque, Dominique, Oubraham, Hassiba, Cohen, Salomon Yves, Gastaud, Pierre, Zambrowsky, Olivia, Creuzot Garcher, Catherine, Said, Saddek Mohand, Garavito, Rocio Blanco, Souied, Eric, Sahel, José-Alain, Audo, Isabelle, Hamel, Christian, Meunier, Isabelle, Clinical Investigation Center - Clinical Research and Epidemiology Unit, Centre Hospitalier Universitaire de Montpellier ( CHU Montpellier ), CIC 1411 Clinical Investigation Center, Institut National de la Santé et de la Recherche Médicale ( INSERM ), CHRU Montpellier, Clin Invest Ctr, Montpellier, France, INSERM, CIC 1411, Montpellier, France, CHRU Montpellier, Clin Res & Epidemiol Unit, Montpellier, France, Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université de Bordeaux ( UB ), U1219 Bordeaux Population Health Research Center, Centre de Référence Maladies Sensorielles Génétiques, Hôpital Gui de Chauliac, Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs ( INM ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Université de Montpellier ( UM ), Eye Clinic, Clinique Sourdille, Centre Ophtalmologique de la Clinique Jules Verne, Service d’Exploration de la Vision et Neuro-ophtalmologie, Hôpital Robert Salengro, Centre Hospitalier Régional Universitaire de Lille ( CHRU de Lille ), Centre Hospitalier Universitaire de Lille ( CHU de Lille ), CIC 1403 Centre d’Investigation Clinique, Université de Lille, Centre Hospitalier Régional Universitaire de Tours ( CHRU TOURS ), CIC 1415 Centre d’Investigation Clinique, Centre Monticelli Paradis d'Ophtalmologie, Hôpital Robert Debré - Eye Clinic, Centre Hospitalier Universitaire de Reims ( CHU de Reims ), Fondation Ophtalmologique Adolphe de Rothschild, Centre d'Imagerie Médicale La Maison Rouge, Centre Ophtalmologique Rabelais, Clinical Investigation Center and Clinical Research and Epidemiology Unit, Centre Hospitalier Intercommunal de Créteil, Centre Ophtalmologique d'Imagerie et de Laser, Centre Hospitalier Universitaire de Nice ( CHU de Nice ), Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Université Bourgogne Franche-Comté ( UBFC ), Eye Clinic - Eye Nutrition and Signaling Group, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), CIC 1423 DHU Sight Restore, Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, Institut de la Vision, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre National de la Recherche Scientifique ( CNRS ), Université Pierre et Marie Curie (Paris 6), Sorbonne Universités, Académie des Sciences, Academie des Sciences, Institute of Ophthalmology, University of Messina, CIC 1423 CIC des Quinze-Vingts - DHU Sight Restor, Laboratoires Thea, Bayer, Novartis, Roche, Ophthotech, Allergan, PHRC, PHRC National, Thea, Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Bordeaux (UB), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Gui de Chauliac [Montpellier], Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Universitaire de Lille (CHU de Lille), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Intercommunal de Créteil (CHIC), Centre Hospitalier Universitaire de Nice (CHU de Nice), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut des Neurosciences de Montpellier (INM), Centre d'Investigation Clinique - Innovation Technologique de Lille - CIC 1403 - CIC 9301 (CIC Lille), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Centre Hospitalier Universitaire de Nice (CHU Nice), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO), Université Pierre et Marie Curie - Paris 6 (UPMC), Sorbonne Université (SU), Académie des Sciences [Paris], Institut de France, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre National de la Recherche Scientifique (CNRS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)
Subjects: Adult, Male, genetic structures, [SDV]Life Sciences [q-bio], Visual Acuity, Retinal Drusen, Diagnostic Techniques, Ophthalmological, Blindness, Macular Degeneration, Risk Factors, Geographic Atrophy, Odds Ratio, Photography, Humans, Sex Distribution, Aged, Aged, 80 and over, [ SDV ] Life Sciences [q-bio], Middle Aged, eye diseases, Choroidal Neovascularization, Case-Control Studies, Disease Progression, Female, France, Tomography, Optical Coherence
Abstract: Purpose: To assess the association of clinical and biological factors with extensive macular atrophy with pseudodrusen (EMAP) characterized by bilateral macular atrophy occurring in patients aged 50 to 60 years and a rapid progression to legal blindness within 5 to 10 years. Design: A national matched case-control study. Participants: Participants were recruited in 10 French Departments of Ophthalmology and their associated clinical investigation centers. All 115 patients with EMAP had symptoms before the age of 55 years due to bilateral extensive macular atrophy with a larger vertical axis and diffuse pseudodrusen. Three controls without age-related macular degeneration (AMD) or retinal disease at fundus examination were matched for each patient with EMAP by gender, age, and geographic area (in total 415). Methods: Subjects and controls underwent an eye examination including color, red-free autofluorescent fundus photographs and spectral-domain optical coherence tomography with macular analysis. The interviews collected demographic, lifestyle, family and personal medical history, medications, and biological data. Associations of risk factors were estimated using conditional logistic regression. Main Outcome Measures: Extensive macular atrophy with pseudodrusen status (cases vs. controls). Results: Extensive macular atrophy with pseudodrusen most frequently affected women (70 women, 45 men). After multivariate adjustment, family history of glaucoma or AMD was strongly associated with EMAP (odds ratio [OR], 2.3, P = 0.008 and OR, 1.5, P = 0.01, respectively). No association was found with cardiac diseases or their risk factors. Mild and moderate kidney disease and higher neutrophil rate were associated with a reduced risk of EMAP (OR, 0.58, P = 0.04; OR, 0.34, P = 0.01; and OR, 0.59, P = 0.003, respectively). On the contrary, eosinophilia (OR, 1.6; P = 0.0002), lymphocytosis (OR, 1.84; P = 0.0002), increased erythrocyte sedimentation rate (OR, 6.5; P = 0.0005), decreased CH50 (P = 0.001), and high plasma C3 level (P = 0.023) were significantly associated with a higher risk of EMAP. Conclusions: This study documents an association between EMAP and family history of AMD and glaucoma, a clear female predominance, and a systemic inflammatory profile. The reduced CH50 and increased C3 plasma values could reflect a more severe complement pathway dysfunction than in AMD, leading to early pseudodrusen and rapid development of geographic atrophy. There is no association of EMAP with AMD cardiac diseases or cardiac risks, including cigarette smoking.
Published: 2016

48. The Influence of Hormonal Factors on the Risk of Developing Cervical Cancer and Pre-Cancer: Results from the EPIC Cohort

Author: María José Sánchez, Jennifer Ose, Antonia Trichopoulou, J. Ramón Quirós, Marc J. Gunter, Xavier Castellsagué, Carlotta Sacerdote, Inger T. Gram, H B As Bueno-de-Mesquita, Johanna Ekström, Ruth C. Travis, Joakim Dillner, Carmen Navarro, Silvia de Sanjosé, Annika Idahl, Renée T. Fortner, Domenico Palli, Noémie Travier, Amalia Mattiello, David Lindquist, Annika Steffen, Elisabete Weiderpass, Christian Munk, Kay-Tee Khaw, Aurelio Barricarte, Elio Riboli, Michael Pawlita, Petra H.M. Peeters, Valeria Pala, Eiliv Lund, Philippos Orfanos, Sabina Rinaldi, F. Xavier Bosch, Pagona Lagiou, Kim Overvad, Nerea Larrañaga, N. Margall, Sylvie Mesrine, Massimo Tommasino, Silvia Franceschi, Silvia Polidoro, Melissa A. Merritt, Tim Waterboer, Giovanna Masala, Agnès Fournier, Rosario Tumino, Esther Roura, Anne Tjønneland, Françoise Clavel-Chapelon, University Medical Center Utrecht, Imperial College Trust, [Roura,E, de Sanjosé,S, Bosch,FX, Castellsagué,X] Unit of Infections and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO)-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Catalonia, Spain. [Roura,E, Sánchez,MJ, Navarro,C, Barricarte,A, Larrañaga,N, Castellsagué,X] CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Travier,N] Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO)-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Catalonia, Spain. [Waterboer,T, Pawlita,M] Division of Molecular Diagnostics of Oncogenic Infections (F020), Research Program Infection, Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.[Pala,V] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Weiderpass, Dillner,J] Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. [Weiderpass,E, Gram,IT, Lund,E] Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway. [Weiderpass,E] Department of Research, Cancer Registry of Norway, Oslo, Norway. Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland. [Margall,N] Microbiology Department, Universitat Autònoma de Barcelona, Hospital de la Santa Creu i Sant Pau, Barcelona, Catalonia, Spain. [Dillner,J] Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden. [Tjønneland,A] Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark. [Munk,C] Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark. [Palli,D, Masala,G] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute–ISPO, Florence, Italy. [Khaw,K] School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom. [Overvad,K] Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark. [Clavel-Chapelon,F, Mesrine,S, Fournier,A] Inserm, Centre for research in Epidemiology and Population Health (CESP), Nutrition, Hormones and Women’s Health team, Villejuif, France. Université Paris Sud, Villejuif, France.Institut Gustave Roussy, Villejuif, France. [Fortne,RT, Ose,J] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Steffen,A] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. [Trichopoulou,A, Orfanos,P] Hellenic Health Foundation, Athens, Greece. [Lagiou,P, Orfanos,P] Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. [Lagiou,P] Department of Epidemiology, Harvard School of Public Health, Boston, United States of America. [Tumino,R] Cancer Registry and Histopathology Unit, 'Civic—M.P. Arezzo' Hospital, Ragusa, Italy. [Sacerdote,C] Unit of Cancer Epidemiology, University of Turin, Turin, Italy. Centre for Cancer Epidemiology and Prevention (CPO Piemonte), Turin, Italy. [Polidoro,S] Human Genetics Foundation (HuGeF), Turin, Italy. [Mattiello,A] Dipartimento Di Medicina Clinica E Chirurgia, Federico II University, Naples, Italy. [Peeters,PH] MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, United Kingdom. Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. [Bueno-de-Mesquita,HB] Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands.[Bueno-de-Mesquita,HB, Merritt,MA, Gunter,MJ, Riboli,E] Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, United Kingdom. [Bueno-de-Mesquita,HB] Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.[Quirós,JR] Public Health Directorate, Asturias, Spain. [Sánchez,MJ] Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain. [Navarro,C] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. Department of Health and Social Sciences, Universidad de Murcia, Murcia, Spain. [Barricarte,A] Navarra Public Health Institute, Pamplona, Spain. Navarra Institute for Health Research (IdiSNA), Pamplona, Spain. [Larrañaga,N] Public Health Division of Gipuzkoa, BIODonostia Research Institute, Basque Health Department, Bilbao, Spain. [Ekström,J] BBMRI.se Service Center for Southern Sweden, Lund University, Medicon Village, Lund, Sweden. [Lindquist,D] Department of Radiation Sciences, Umeå University, Umeå, Sweden. [Idahl,A] Department of Clinical Sciences, Obstetrics and Gynecology, Umeå University, Umeå, Sweden. [Travis,RC] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. [Rinaldi,S, Tommasino,M, Franceschi,S] International Agency for Research on Cancer, Lyon, France., Funding: The work was partially supported by grants from the Instituto de Salud Carlos III (Spanish Government) (grants FIS PI08/1308, PI13/00053, RCESP C03/09, RTICESP C03/10, RTIC RD06/0020/0095, RD12/0036/0056, RD12/0036/0018, and CIBERESP) and from the Agència de Gestió d’Ajuts Universitaris i de Recerca – Generalitat de Catalunya (Catalonian Government) (grants AGAUR 2005SGR00695, 2009SGR939 and 2009SGR126, 2014SGR1077, 2014SGR2016). The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by the Health Research Fund (FIS) of the Spanish Ministry of Health (Exp P10710130), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236), Navarra and the Catalan Institute of Oncology, La Caixa (BM 06-130), RTICC-RD06/10091 (Spain), Danish Cancer Society (Denmark), Ligue contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation (Greece), Italian Association for Research on Cancer (AIRC) and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF) and Statistics Netherlands (The Netherlands), Swedish Cancer Society, Swedish Scientific Council and Regional Government of Skåne and Västerbotten (Sweden), Cancer Research UK, Medical Research Council (United Kingdom), and Norwegian Research Council, Norwegian Cancer Society, University of Tromso (Norway).
Subjects: Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Carcinoma in Situ::Cervical Intraepithelial Neoplasia [Medical Subject Headings], Oncology, Replacement therapy, Pathology and Laboratory Medicine, Antibodies, Viral, Biochemistry, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Pregnancy, Prospective Studies, lcsh:Science, Gonadal Steroid Hormones, education.field_of_study, Hormonal Therapy, Contraceptives, Humanos, Anticonceptivos, 030220 oncology & carcinogenesis, Cohort, Carcinoma, Squamous Cell, Cohort studies, Science & Technology - Other Topics, Intreaepithelial neoplasia, Human, Cohort study, Oral, Human Papillomavirus Infection, medicine.medical_specialty, Càncer de coll uterí, Sexually Transmitted Diseases, Estudios retrospectivos, 03 medical and health sciences, Drug Therapy, Diseases::Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms, Female::Uterine Neoplasms::Uterine Cervical Neoplasms [Medical Subject Headings], Neoplasias del cuello uterino, Humans, education, Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Parity [Medical Subject Headings], Aged, Pharmacology, Gynecology, Cancer och onkologi, Science & Technology, Herpes Genitalis, Genitourinary Infections, Herpesvirus 2, lcsh:R, Case-control study, Biology and Life Sciences, Estrogens, medicine.disease, Hormones, 030104 developmental biology, Check Tags::Female [Medical Subject Headings], Cancer and Oncology, Case-Control Studies, Cervical cancer, Medical Devices and Equipment, lcsh:Q, Intrauterine Devices, 0301 basic medicine, Glutathione-S-transferase, Viral Diseases, Human papillomavirus infection, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies::Retrospective Studies [Medical Subject Headings], Herpesvirus 2, Human, lcsh:Medicine, Uterine Cervical Neoplasms, Chlamydia trachomatis, Cervical Cancer, Cohort Studies, Cervix cancer, Paridad, Medicine and Health Sciences, Viral, Non-U.S. Gov't, Prospective cohort study, Papillomaviridae, Reproductive History, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Reproductive Control Agents::Contraceptive Agents [Medical Subject Headings], Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Reproductive Physiological Processes::Reproduction::Pregnancy [Medical Subject Headings], Multidisciplinary, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings], Pharmaceutics, Research Support, Non-U.S. Gov't, Femenino, Drugs, Estudios de Casos y Controles, Middle Aged, humanities, Multidisciplinary Sciences, Infectious Diseases, Serology, Research Design, Hormonal therapy, Female, Research Article, Biotechnology, Adult, Risk, Papillomaviruses, Embarazo, General Science & Technology, Hormone Replacement Therapy, Urology, Population, Individual data, Research Support, Research and Analysis Methods, Cervical intraepithelial neoplasia, Antibodies, Contraceptives, Oral, Hormonal, Young Adult, Collaborative reanalysis, Internal medicine, Oral-contraceptives, MD Multidisciplinary, Journal Article, medicine, Multicentric case-control, Cervical Intraepithelial Neoplasia, Neoplasia Intraepitelial Cervical, Papil·lomavirus, Reproductive factors, Hormonal, business.industry, Carcinoma, Papillomavirus Infections, Cancers and Neoplasms, Chlamydia Infections, Uterine Cervical Dysplasia, Squamous Cell, Organisms::Viruses::DNA Viruses::Papillomaviridae [Medical Subject Headings], business, Gynecological Tumors, Follow-Up Studies
Abstract: The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by the Health Research Fund (FIS) of the Spanish Ministry of Health (Exp P10710130) In addition to HPV, high parity and hormonal contraceptives have been associated with cervical cancer (CC). However, most of the evidence comes from retrospective case-control studies. The aim of this study is to prospectively evaluate associations between hormonal factors and risk of developing cervical intraepithelial neoplasia grade 3 (CIN3)/carcinoma in situ (CIS) and invasive cervical cancer (ICC). We followed a cohort of 308,036 women recruited in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study. At enrollment, participants completed a questionnaire and provided serum. After a 9-year median follow-up, 261 ICC and 804 CIN3/CIS cases were reported. In a nested case-control study, the sera from 609 cases and 1,218 matched controls were tested for L1 antibodies against HPV types 11,16,18,31,33,35,45,52,58, and antibodies against Chlamydia trachomatis and Human herpesvirus 2. Multivariate analyses were performed to estimate hazard ratios (HR), odds ratios (OR) and corresponding 95% confidence intervals (CI). The cohort analysis showed that number of full-term pregnancies was positively associated with CIN3/CIS risk (p-trend = 0.03). Duration of oral contraceptives use was associated with a significantly increased risk of both CIN3/CIS and ICC (HR = 1.6 and HR = 1.8 respectively for ≥15 years versus never use). Ever use of menopausal hormone therapy was associated with a reduced risk of ICC (HR = 0.5, 95%CI: 0.4-0.8). A non-significant reduced risk of ICC with ever use of intrauterine devices (IUD) was found in the nested case-control analysis (OR = 0.6). Analyses restricted to all cases and HPV seropositive controls yielded similar results, revealing a significant inverse association with IUD for combined CIN3/CIS and ICC (OR = 0.7). Even though HPV is the necessary cause of CC, our results suggest that several hormonal factors are risk factors for cervical carcinogenesis. Adherence to current cervical cancer screening guidelines should minimize the increased risk of CC associated with these hormonal risk factors.
Published: 2016

49. A Nested Case-Control Study of Metabolically Defined Body Size Phenotypes and Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Author: Murphy, N, Cross, A, Abubakar, M, Jenab, M, Aleksandrova, K, Boutron-Ruault, M, Dossus, L, Racine, A, Kühn, T, Katzke, V, Tjønneland, A, Petersen, K, Overvad, K, Quirós, JR, Jakszyn, P, Molina-Montes, E, Dorronsoro, M, Huerta, J, Barricarte, A, Khaw, K, Wareham, N, Travis, R, Trichopoulou, A, Lagiou, P, Trichopoulos, D, Masala, G, Krogh, V, Tumino, R, Vineis, P, Panico, S, Bueno-de-Mesquita, H, Siersema, P, Peeters, P, Ohlsson, B, Ericson, U, Palmqvist, R, Nyström, H, Weiderpass, E, Skeie, G, Freisling, H, Kong, S, Tsilidis, K, Muller, D, Riboli, E, Gunter, M, [Murphy,N, Cross,AJ, Vineis,P, Bueno-de-Mesquita,HB, Tsilidis,K, Riboli,E, Gunter,MJ] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.[Abubakar,M] Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, United Kingdom. [Jenab,M, Freisling,M, Kong,SY, Mulle,DC, Gunter,MJ] International Agency for Research on Cancer, World Health Organization, Lyon, France. [Aleksandrova,K] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Potsdam, Germany. [Boutron-Ruault,M, Dossus,L, Racine,A] Inserm, Nutrition, Hormones and Women’s Health, Centre for Research in Epidemiology and Population Health (CESP), U1018, Villejuif, France. Université Paris Sud, UMRS 1018, Villejuif, France. Institut Gustave Roussy, Villejuif, France. [Kühn,T, Katzke,VA] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Tjønneland,A, Petersen,KEN] Danish Cancer Society Research Center, Copenhagen, Denmark. [Overvad,K] Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark. [Quirós,JR] Public Health Directorate, Asturias, Spain. [Jakszyn,P] Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology, Barcelona, Spain. [Molina-Montes,E] Andalusian School of Public Health, Granada, Spain. [Molina-Montes,E, Huerta,J, Barricarte,A] Biomedical Research Centre Network for Epidemiology and Public Health (CIBERESP), Madrid, Spain. [Dorronsoro,M] Public Health Direction and Biodonostia–CIBERESP, Basque Regional Health Department, Vitoria, Spain. [Huerta,J] Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain. [Barricarte,A] Navarre Public Health Institute, Pamplona, Spain. [Khaw,K] University of Cambridge, Cambridge, United Kingdom. [Wareham,N] MRC Epidemiology Unit, Cambridge, United Kingdom. [Travis,RC] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. [Trichopoulou,A, Trichopoulos,D] Hellenic Health Foundation, Athens, Greece. [Trichopoulou,A, Lagiou,P] Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. [Trichopoulou,A, Lagiou,P, Trichopoulos,D] Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. [Lagiou,P, Trichopoulos,D] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America. [Masala,G] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy. [Krogh,V] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, Civic–M.P.Arezzo Hospital, Azienda Sanitaria Provinciale di Ragusa, Italy. [Vineis,P] HuGeF Foundation, Torino, Italy. [Panico,S] Dipartimento di Medicina Clinica e Sperimentale, Federico II University, Naples, Italy. [Bueno-de- Mesquita,HB] Department of Determinants of Chronic Diseases, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia [Bueno-de-Mesquita,HB, Siersema,PD] Department of Gastroenterology and Hepatology, University Medical Centre Utrecht, Utrecht, The Netherlands. [Peeters,PH] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. [Ohlsson,B] Division of Internal Medicine, Department of Clinical Sciences, Skåne University Hospital, Lund University, Malmö, Sweden. [Ericson,U] Diabetes and Cardiovascular Disease–Genetic Epidemiology, Department of Clinical Sciences, Skåne University Hospital, Lund University, Malmö, Lund University, Sweden. [Palmqvist,R, Nyström,H] Medical Bioscience, Umeå University, Umeå, Sweden. [Weiderpass,E, Skeie,G] Department of Community Medicine, Faculty of Health Sciences, University of Tromsø–The Arctic University of Norway, Tromsø, Norway. [Weiderpass,E] Cancer Registry of Norway, Oslo, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Department of Genetic Epidemiology, Folkhälsan Research Center, Helsinki, Finland. [Tsilidis,K] Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece., Funding: The coordination of EPIC is financially supported by the European Commission (DGSANCO), and the International Agency for Research on Cancer., University Medical Center Utrecht, Imperial College Trust, Murphy, Neil, Cross, Amanda J, Abubakar, Mustapha, Jenab, Mazda, Aleksandrova, Krasimira, Boutron Ruault, Marie Christine, Dossus, Laure, Racine, Antoine, Kühn, Tilman, Katzke, Verena A, Tjønneland, Anne, Petersen, Kristina E. N, Overvad, Kim, Quirós, J. Ramón, Jakszyn, Paula, Molina Montes, Esther, Dorronsoro, Miren, Huerta, José María, Barricarte, Aurelio, Khaw, Kay Tee, Wareham, Nick, Travis, Ruth C, Trichopoulou, Antonia, Lagiou, Pagona, Trichopoulos, Dimitrio, Masala, Giovanna, Krogh, Vittorio, Tumino, Rosario, Vineis, Paolo, Panico, Salvatore, Bueno de Mesquita, H. Ba, Siersema, Peter D, Peeters, Petra H, Ohlsson, Bodil, Ericson, Ulrika, Palmqvist, Richard, Nyström, Hanna, Weiderpass, Elisabete, Skeie, Guri, Freisling, Heinz, Kong, So Yeon, Tsilidis, Kosta, Muller, David C, Riboli, Elio, Gunter, Marc J., Khaw, Kay-Tee [0000-0002-8802-2903], Wareham, Nicholas [0000-0003-1422-2993], and Apollo - University of Cambridge Repository
Subjects: Male, Phenomena and Processes::Genetic Phenomena::Phenotype [Medical Subject Headings], Cell- och molekylärbiologi, Obesidad, Biochemistry, Body Mass Index, Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14], Endocrinology, Odds Ratio, Insulin, Prospective Studies, Diseases::Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Body Weight::Overweight [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Vital Statistics::Morbidity::Prevalence [Medical Subject Headings], Adiposity, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, C-Peptide, Incidence, 11 Medical And Health Sciences, Oncology, Medicine, Waist Circumference, Fenotipo, Human, Logistic Model, Colon, Risk Assessment, Hyperinsulinism, Gastrointestinal Tumors, Neoplasias Colorrectales, Humans, Comparative Study, Diseases::Cardiovascular Diseases [Medical Subject Headings], Protective Factor, Cancer och onkologi, Chi-Square Distribution, Biology and Life Sciences, nutritional and metabolic diseases, Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [Medical Subject Headings], Biomarker, Hormones, Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::Obesity [Medical Subject Headings], Prospective Studie, Logistic Models, Case-Control Studies, Cancer and Oncology, Digestive System, Biomarkers, Cell and Molecular Biology, Metabolic Processes, Physiology, Health Status, Colorectal Neoplasm, Health Statu, Risk Factors, Medicine and Health Sciences, Body Size, Multivariate Analysi, Tamaño Corporal, Enfermedades Cardiovasculares, Medicine(all), Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings], Research Support, Non-U.S. Gov't, Estudios de Casos y Controles, Estudios Prospectivos, Middle Aged, Multicenter Study, Europe, Phenotype, Physiological Parameters, Female, Anatomy, Colorectal Neoplasms, Case-Control Studie, Research Article, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Physical Examination::Body Constitution::Body Weights and Measures::Body Size [Medical Subject Headings], Rectal Cancer, Research Support, N.I.H., Extramural, General & Internal Medicine, Journal Article, Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Hyperinsulinism [Medical Subject Headings], Obesity, Colorectal Cancer, Diabetic Endocrinology, Obesity, Metabolically Benign, Hiperinsulinismo, Risk Factor, Body Weight, Cancers and Neoplasms, Protective Factors, Gastrointestinal Tract, Metabolism, Sobrepeso, Multivariate Analysis, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, Prevalencia
Abstract: Background Obesity is positively associated with colorectal cancer. Recently, body size subtypes categorised by the prevalence of hyperinsulinaemia have been defined, and metabolically healthy overweight/obese individuals (without hyperinsulinaemia) have been suggested to be at lower risk of cardiovascular disease than their metabolically unhealthy (hyperinsulinaemic) overweight/obese counterparts. Whether similarly variable relationships exist for metabolically defined body size phenotypes and colorectal cancer risk is unknown. Methods and Findings The association of metabolically defined body size phenotypes with colorectal cancer was investigated in a case–control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Metabolic health/body size phenotypes were defined according to hyperinsulinaemia status using serum concentrations of C-peptide, a marker of insulin secretion. A total of 737 incident colorectal cancer cases and 737 matched controls were divided into tertiles based on the distribution of C-peptide concentration amongst the control population, and participants were classified as metabolically healthy if below the first tertile of C-peptide and metabolically unhealthy if above the first tertile. These metabolic health definitions were then combined with body mass index (BMI) measurements to create four metabolic health/body size phenotype categories: (1) metabolically healthy/normal weight (BMI < 25 kg/m2), (2) metabolically healthy/overweight (BMI ≥ 25 kg/m2), (3) metabolically unhealthy/normal weight (BMI < 25 kg/m2), and (4) metabolically unhealthy/overweight (BMI ≥ 25 kg/m2). Additionally, in separate models, waist circumference measurements (using the International Diabetes Federation cut-points [≥80 cm for women and ≥94 cm for men]) were used (instead of BMI) to create the four metabolic health/body size phenotype categories. Statistical tests used in the analysis were all two-sided, and a p-value of, Gunter and colleagues analyse a large European dataset to determine how body size and metabolic profile associates with the risk of developing colorectal cancer., Editors' Summary Background Colorectal cancer is the third most common cancer worldwide and is a leading cause of cancer-related death, killing around 700,000 people every year. It develops when cells in the colon (the final part of the digestive system, which is also known as the large intestine or large bowel) or the rectum (the lower end of the colon) acquire genetic changes that allow them to divide uncontrollably to form a tumor and to move around the body (metastasize). Symptoms of colorectal cancer include blood in the stool, a change in bowel habits, and unexplained weight loss. Treatments for colorectal cancer include surgery, chemotherapy, and radiation. As with other types of cancer, these treatments are more likely to be successful if started when the tumor is very small. Consequently, many countries run screening programs that use colonoscopy, the fecal occult blood test, and other tests to detect the earliest signs of colorectal cancer in apparently healthy people. Why Was This Study Done? Being obese—having too much body fat—is associated with an increased colorectal cancer risk (other risk factors include age, having a family history of colorectal cancer, and eating a high-fat, low-fiber diet). Obesity is also associated with several other chronic diseases, and recent evidence suggests that some obese individuals have a higher risk of developing these diseases than others. For example, overweight/obese individuals who have hyperinsulinemia (abnormally high blood levels of insulin; “metabolically unhealthy”) seem to have a higher risk of cardiovascular disease than their non-hyperinsulinemic (“metabolically healthy”) overweight counterparts. If certain combinations of metabolic health status and body size (“metabolically defined body size phenotypes”) are also associated with colorectal cancer, measurement of insulin levels in conjunction with body fat (adiposity) measurements such as body mass index (BMI; an indicator of body fat calculated by dividing a person’s weight in kilograms by their height in meters squared) might improve colorectal cancer risk assessment. In this nested case–control study, the researchers assess the associations between metabolically defined body size phenotypes and colorectal cancer risk. A nested case–control study identifies everyone in a group (here, participants in the European Prospective Investigation into Cancer and Nutrition [EPIC] study) who has a specific condition, identifies matched individuals in the same group without the condition, and asks whether these controls and the cases differ in terms of a specific characteristic or outcome. What Did the Researchers Do and Find? The researchers matched 737 participants in the EPIC study who developed colorectal cancer after study enrollment with 737 controls and used serum concentrations of C-peptide, a marker of insulin secretion, and BMI measurements to classify each individual as metabolically healthy/normal weight, metabolically healthy/overweight, metabolically unhealthy/normal weight, or metabolically unhealthy/overweight. Specifically, the researchers categorized people as metabolically unhealthy if they had a C-peptide level above an arbitrarily chosen cut-off value based on the distribution of C-peptide levels in the control participants and as overweight if they had a BMI of ≥25 kg/m2 (the standard definition of overweight). Compared to metabolically healthy normal weight individuals, metabolically unhealthy normal weight and overweight individuals had an increased colorectal cancer risk; metabolically healthy overweight individuals had a similar colorectal cancer risk to metabolically healthy normal weight individuals. Among overweight individuals, metabolically healthy individuals had a lower colorectal cancer risk than metabolically unhealthy individuals. Finally, similar associations were seen when the researchers used waist circumference instead of BMI as the measure of adiposity. What Do These Findings Mean? These findings suggest that normal weight individuals with hyperinsulinemia (the metabolically unhealthy normal weight phenotype) have a higher risk of colorectal cancer than normal weight individuals without hyperinsulinemia. They also suggest that metabolically unhealthy overweight individuals have a higher risk of colorectal cancer than metabolically healthy overweight individuals. The accuracy of these findings may be limited by the method the researchers used to classify individuals as hyperinsulinemic—there is no universally accepted clinical definition for using C-peptide level to diagnose hyperinsulinemia. Nevertheless, these findings suggest that the assessment of insulin levels in conjunction with adiposity measures might be a better way to assess an individual’s colorectal cancer risk than simply measuring adiposity, and might help to identify those individuals at high risk of colorectal cancer who are most likely to benefit from targeted interventions designed to prevent the onset of clinical disease. Additional Information This list of resources contains links that can be accessed when viewing the PDF on a device or via the online version of the article at http://dx.doi.org/10.1371/journal.pmed.1001988. The US National Cancer Institute provides information for patients about all aspects of colorectal cancer; it also provides more detailed information colorectal cancer for health professionals and information on cancer risk and obesity The UK National Health Service Choices website has information and personal stories about colorectal cancer and information on obesity The not-for-profit organization Cancer Research UK provides information about colorectal cancer and about the association between cancer and obesity MedlinePlus provides links to further resources about colorectal cancer and about obesity Wikipedia has a page on hyperinsulinemia (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages) More information about the EPIC study is available
Published: 2016

50. Cellular immune activity biomarker neopterin is associated hyperlipidemia: results from a large population-based study

Author: Per Magne Ueland, Anne Tjønneland, Nicholas J. Wareham, Petra H.M. Peeters, Richard Palmqvist, Stein Emil Vollset, Marc J. Gunter, Kim Overvad, Miren Dorronsoro, Amanda J. Cross, Giovanna Masala, J. Ramón Quirós, Øivind Midttun, Krasimira Aleksandrova, Dimitrios Trichopoulos, Aurelio Barricarte, Yunxia Lu, Ruth C. Travis, Bas Bueno-de-Mesquita, Tilman Kuehn, Shu Chun Chuang, Claudia Agnoli, José María Huerta, Tobias Pischon, Martin Lajous, Heiner Boeing, Marie-Christine Boutron-Ruault, Pagona Lagiou, Antonia Trichopoulou, Guy Fagherazzi, Rosario Tumino, Rudolf Kaaks, Kay-Tee Khaw, Amalia Mattiello, Antonio Agudo, Esther Molina-Montes, Dagmar Drogan, Elisabete Weiderpass, Paolo Vineis, Elio Riboli, Ingrid Ljuslinder, University Medical Center Utrecht, Imperial College Trust, [Chuang,S] Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli County, Taiwan.[Chuang,S, Bueno-de-Mesquita,B, Peeter,PH, Gunter,M, Lu,Y, Cross,AJ, Riboli,E, Vineis,P] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Boeing,H] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. [Vollset,SE] Department of Public Health and Primary Health Care, University of Bergen, Bergen, Norway. Division of Epidemiology, Norwegian Institute of Public Health, Bergen, Norway. [Midttun,O] Bevital AS, Bergen, Norway. [Ueland,PM] Department of Clinical Science, University of Bergen, Bergen, Norway. Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway. [Bueno-de-Mesquita,B] The National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands. Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. [Lajous,M, Fagherazzi,G, Boutron-Ruault,M] Inserm, Centre for research in Epidemiology and Population Health (CESP), Nutrition, Hormones and Women’s Health team, Villejuif, France. University of Paris Sud, Villejuif, France. IGR, Villejuif, France. [Kaaks,R, Küehn,T] Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany. [Pischon,T] Molecular Epidemiology Group, Max Delbrueck Center for Molecular Medicine (MDC), Berlin-Buch, Germany. [Drogan,D] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany. [Tjønneland,A] Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark. [Overvad,K] Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark. [Quirós,JR] Public Health Directorate, Asturias, Oviedo, Spain. [Agudo,A] Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology-ICO, IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain. [Molina-Montes,E] Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria de Granada (Granada.ibs), Granada, Spain. [Molina-Montes,E, Huerta,JM] Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiología y Salud Pública-CIBERESP), Madrid, Spain. [Dorronsoro,M] Epidemiology and Health Information, Public Health Division of Gipuzkoa, Basque Regional Health Department, San Sebastian, Spain. [Huerta,JM] Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain. [Barricarte,A] Navarre Public Health Institute, Pamplona, Spain. [Khaw,K] Clinical Gerontology Unit, Addenbrooke’s Hospital, University of Cambridge School of Clinical Medicine, Cambridge, UK. [Wareham,NJ] MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, UK. [Travis,RC, Trichopoulou,A] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. [Trichopoulou,A, Trichopoulos,D] Hellenic Health Foundation, Athens, Greece. [Lagiou,P] Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. Department of Epidemiology, Harvard School of Public Health, Boston, USA. [Lagiou,P, Trichopoulos,D] Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. [Masala,G] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO, Florence, Italy. [Agnoli,C] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, 'Civic - M.P. Arezzo' Hospital, ASP Ragusa, Italy. [Mattiello,A] Dipartamento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy. [Peeters,PH] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. [Weiderpass,E] Department of Community Medicine, Faculty of Health Sciences, University of Tromso, Tromsø, Norway. Department of Research, Cancer Registry of Norway, Oslo, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Samfundet Folkhälsan, Helsinki, Finland. [Palmqvist,R] Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden. [Ljuslinder,I] Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden. [Aleksandrova,K] Nutrition, Immunity and Metabolism Start-up Lab, Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany., The EPIC cohort is supported by the Europe Against Cancer Program of the European Commission (SANCO). The individual centers also received funding from: Denmark: Danish Cancer Society, France: Ligue centre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM), Greece: the Hellenic Health Foundation, the Stavros Niarchos Foundation, and the Hellenic Ministry of Health and Social Solidarity, Germany : German Cancer Aid, and Federal Ministry of Education and Research, Italy: Italian Association for Research on Cancer and the National Research Council, The Netherlands: Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands, Norway: Helga – Nordforsk centre of excellence in food, nutrition and health and The Norwegian Extra Foundation for Health and Rehabilitation, The Norwegian Cancer Society, Spain: Health Research Fund (FIS) of the Spanish Ministry of Health (Exp 96/0032, RETICC DR06/ 0020), the Spanish Regional Governments of Andalusia, Asturias, Basque Country, Murcia (N0 6236), and the Navarra and the Catalan Institute of Oncology, Sweden: Swedish Cancer Society, Swedish Scientific Council, and Regional Governments of Skane and Västerbotten, UK: Cancer Research UK and Medical Research Council. Grant supports for the biochemical measurements: HDL-C and TG were analysed with additional support from the Ministry of Public Health, Welfare and Sports, the Netherlands,German Cancer Aid, Federal Ministry for Education and Research, European Union, European Union and AIRC-ITALY , German Cancer Aid, Federal Ministry for Education and Research, European Union, Stavros Niarchos Foundation , Hellenic Ministry of Health, Hellenic Health Foundation, MRC and Cancer Research UK, and Hba1c was analysed with additional support from National Cancer Institute grant 1RO1CA102460 and data analyses on CRP were performed with support from World Cancer Research Fund International and Wereld Kanker Onderzoek Fonds (WCRF NL)
Subjects: 0301 basic medicine, Aging, Síndrome metabòlica, Geriatrics & Gerontology, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Methods::Research Design [Medical Subject Headings], 030204 cardiovascular system & hematology, Cardiovascular, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, immune system diseases, GENETIC-VARIANTS, Hyperlipidemia, HORDALAND HEALTH, Metabolic syndrome, Cell-mediated immunity, Neopterin, Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes [Medical Subject Headings], 3. Good health, European Prospective Investigation into Cancer and Nutrition, PROGNOSTIC VALUE, Neopterina, Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Lipid Metabolism Disorders::Dyslipidemias::Hyperlipidemias [Medical Subject Headings], 1107 Immunology, Biomarker (medicine), CORONARY-ARTERY-DISEASE, Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 2-Ring::Pteridines::Pterins::Biopterin::Neopterin [Medical Subject Headings], Life Sciences & Biomedicine, SERUM NEOPTERIN, medicine.medical_specialty, Clinical Sciences, Immunology, Clinical nutrition, Procesos Bioquímicos, ADVERSE CARDIAC EVENTS, 03 medical and health sciences, Clinical Research, Internal medicine, medicine, Journal Article, Nutrition, COLORECTAL-CANCER RISK, Cancer och onkologi, Proyectos de Investigación, Science & Technology, INTERFERON-GAMMA, business.industry, Research, 1103 Clinical Sciences, medicine.disease, Ageing, 030104 developmental biology, Blood pressure, Endocrinology, SYSTEM ACTIVATION, chemistry, Cardiovascular and Metabolic Diseases, Cancer and Oncology, Glycated hemoglobin, Hiperlipidemias, business, Hiperlipèmia
Abstract: BACKGROUND: Increased serum neopterin had been described in older age two decades ago. Neopterin is a biomarker of systemic adaptive immune activation that could be potentially implicated in metabolic syndrome (MetS). Measurements of waist circumference, triglycerides, high-density lipoprotein cholesterol (HDLC), systolic and diastolic blood pressure, glycated hemoglobin as components of MetS definition, and plasma total neopterin concentrations were performed in 594 participants recruited in the European Prospective Investigation into Cancer and Nutrition (EPIC).RESULTS: Higher total neopterin concentrations were associated with reduced HDLC (9.7 %, p CONCLUSIONS: These data suggest that high total neopterin concentrations are cross-sectionally associated with reduced HDLC, but not with overall MetS.
Published: 2016

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