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1. Ancestry-driven metabolite variation provides insights into disease states in admixed populations

Author: Kaylia M. Reynolds, Andrea R. V. R. Horimoto, Bridget M. Lin, Ying Zhang, Nuzulul Kurniansyah, Bing Yu, Eric Boerwinkle, Qibin Qi, Robert Kaplan, Martha Daviglus, Lifang Hou, Laura Y. Zhou, Jianwen Cai, Saame Raza Shaikh, Tamar Sofer, Sharon R. Browning, and Nora Franceschini
Subjects: Admixture mapping, Local ancestry, Metabolites, Hispanics/Latino populations, Medicine, Genetics, QH426-470
Abstract: Abstract Background Metabolic pathways are related to physiological functions and disease states and are influenced by genetic variation and environmental factors. Hispanics/Latino individuals have ancestry-derived genomic regions (local ancestry) from their recent admixture that have been less characterized for associations with metabolite abundance and disease risk. Methods We performed admixture mapping of 640 circulating metabolites in 3887 Hispanic/Latino individuals from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Metabolites were quantified in fasting serum through non-targeted mass spectrometry (MS) analysis using ultra-performance liquid chromatography-MS/MS. Replication was performed in 1856 nonoverlapping HCHS/SOL participants with metabolomic data. Results By leveraging local ancestry, this study identified significant ancestry-enriched associations for 78 circulating metabolites at 484 independent regions, including 116 novel metabolite-genomic region associations that replicated in an independent sample. Among the main findings, we identified Native American enriched genomic regions at chromosomes 11 and 15, mapping to FADS1/FADS2 and LIPC, respectively, associated with reduced long-chain polyunsaturated fatty acid metabolites implicated in metabolic and inflammatory pathways. An African-derived genomic region at chromosome 2 was associated with N-acetylated amino acid metabolites. This region, mapped to ALMS1, is associated with chronic kidney disease, a disease that disproportionately burdens individuals of African descent. Conclusions Our findings provide important insights into differences in metabolite quantities related to ancestry in admixed populations including metabolites related to regulation of lipid polyunsaturated fatty acids and N-acetylated amino acids, which may have implications for common diseases in populations.
Published: 2023
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2. Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity

Author: Tuomas O. Kilpeläinen, Amy R. Bentley, Raymond Noordam, Yun Ju Sung, Karen Schwander, Thomas W. Winkler, Hermina Jakupović, Daniel I. Chasman, Alisa Manning, Ioanna Ntalla, Hugues Aschard, Michael R. Brown, Lisa de las Fuentes, Nora Franceschini, Xiuqing Guo, Dina Vojinovic, Stella Aslibekyan, Mary F. Feitosa, Minjung Kho, Solomon K. Musani, Melissa Richard, Heming Wang, Zhe Wang, Traci M. Bartz, Lawrence F. Bielak, Archie Campbell, Rajkumar Dorajoo, Virginia Fisher, Fernando P. Hartwig, Andrea R. V. R. Horimoto, Changwei Li, Kurt K. Lohman, Jonathan Marten, Xueling Sim, Albert V. Smith, Salman M. Tajuddin, Maris Alver, Marzyeh Amini, Mathilde Boissel, Jin Fang Chai, Xu Chen, Jasmin Divers, Evangelos Evangelou, Chuan Gao, Mariaelisa Graff, Sarah E. Harris, Meian He, Fang-Chi Hsu, Anne U. Jackson, Jing Hua Zhao, Aldi T. Kraja, Brigitte Kühnel, Federica Laguzzi, Leo-Pekka Lyytikäinen, Ilja M. Nolte, Rainer Rauramaa, Muhammad Riaz, Antonietta Robino, Rico Rueedi, Heather M. Stringham, Fumihiko Takeuchi, Peter J. van der Most, Tibor V. Varga, Niek Verweij, Erin B. Ware, Wanqing Wen, Xiaoyin Li, Lisa R. Yanek, Najaf Amin, Donna K. Arnett, Eric Boerwinkle, Marco Brumat, Brian Cade, Mickaël Canouil, Yii-Der Ida Chen, Maria Pina Concas, John Connell, Renée de Mutsert, H. Janaka de Silva, Paul S. de Vries, Ayşe Demirkan, Jingzhong Ding, Charles B. Eaton, Jessica D. Faul, Yechiel Friedlander, Kelley P. Gabriel, Mohsen Ghanbari, Franco Giulianini, Chi Charles Gu, Dongfeng Gu, Tamara B. Harris, Jiang He, Sami Heikkinen, Chew-Kiat Heng, Steven C. Hunt, M. Arfan Ikram, Jost B. Jonas, Woon-Puay Koh, Pirjo Komulainen, Jose E. Krieger, Stephen B. Kritchevsky, Zoltán Kutalik, Johanna Kuusisto, Carl D. Langefeld, Claudia Langenberg, Lenore J. Launer, Karin Leander, Rozenn N. Lemaitre, Cora E. Lewis, Jingjing Liang, Lifelines Cohort Study, Jianjun Liu, Reedik Mägi, Ani Manichaikul, Thomas Meitinger, Andres Metspalu, Yuri Milaneschi, Karen L. Mohlke, Thomas H. Mosley, Alison D. Murray, Mike A. Nalls, Ei-Ei Khaing Nang, Christopher P. Nelson, Sotoodehnia Nona, Jill M. Norris, Chiamaka Vivian Nwuba, Jeff O’Connell, Nicholette D. Palmer, George J. Papanicolau, Raha Pazoki, Nancy L. Pedersen, Annette Peters, Patricia A. Peyser, Ozren Polasek, David J. Porteous, Alaitz Poveda, Olli T. Raitakari, Stephen S. Rich, Neil Risch, Jennifer G. Robinson, Lynda M. Rose, Igor Rudan, Pamela J. Schreiner, Robert A. Scott, Stephen S. Sidney, Mario Sims, Jennifer A. Smith, Harold Snieder, Tamar Sofer, John M. Starr, Barbara Sternfeld, Konstantin Strauch, Hua Tang, Kent D. Taylor, Michael Y. Tsai, Jaakko Tuomilehto, André G. Uitterlinden, M. Yldau van der Ende, Diana van Heemst, Trudy Voortman, Melanie Waldenberger, Patrik Wennberg, Gregory Wilson, Yong-Bing Xiang, Jie Yao, Caizheng Yu, Jian-Min Yuan, Wei Zhao, Alan B. Zonderman, Diane M. Becker, Michael Boehnke, Donald W. Bowden, Ulf de Faire, Ian J. Deary, Paul Elliott, Tõnu Esko, Barry I. Freedman, Philippe Froguel, Paolo Gasparini, Christian Gieger, Norihiro Kato, Markku Laakso, Timo A. Lakka, Terho Lehtimäki, Patrik K. E. Magnusson, Albertine J. Oldehinkel, Brenda W. J. H. Penninx, Nilesh J. Samani, Xiao-Ou Shu, Pim van der Harst, Jana V. Van Vliet-Ostaptchouk, Peter Vollenweider, Lynne E. Wagenknecht, Ya X. Wang, Nicholas J. Wareham, David R. Weir, Tangchun Wu, Wei Zheng, Xiaofeng Zhu, Michele K. Evans, Paul W. Franks, Vilmundur Gudnason, Caroline Hayward, Bernardo L. Horta, Tanika N. Kelly, Yongmei Liu, Kari E. North, Alexandre C. Pereira, Paul M. Ridker, E. Shyong Tai, Rob M. van Dam, Ervin R. Fox, Sharon L. R. Kardia, Ching-Ti Liu, Dennis O. Mook-Kanamori, Michael A. Province, Susan Redline, Cornelia M. van Duijn, Jerome I. Rotter, Charles B. Kooperberg, W. James Gauderman, Bruce M. Psaty, Kenneth Rice, Patricia B. Munroe, Myriam Fornage, L. Adrienne Cupples, Charles N. Rotimi, Alanna C. Morrison, Dabeeru C. Rao, and Ruth J. F. Loos
Subjects: Science
Abstract: GWAS have identified more than 500 genetic loci associated with blood lipid levels. Here, the authors report a genome-wide analysis of interactions between genetic markers and physical activity, and find that physical activity modifies the effects of four genetic loci on HDL or LDL cholesterol.
Published: 2019
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3. Multi-ancestry sleep-by-SNP interaction analysis in 126,926 individuals reveals lipid loci stratified by sleep duration

Author: Sina A. Gharib, Kenneth Rice, Donna K. Arnett, Tõnu Esko, Annemarie I. Luik, Niki Dimou, Dabeeru C. Rao, Pamela J. Schreiner, Melissa A. Richard, Reedik Mägi, Nicholette D. Palmer, Stefan Weiss, Han Chen, Solomon K. Musani, W. James Gauderman, Christian Gieger, Kari E. North, Salman M. Tajuddin, Diana van Heemst, Rainer Rauramaa, Stephen B. Kritchevsky, Henry Völzke, Minjung Kho, Michele K. Evans, Ruth J. F. Loos, Correa Adolfo, Pedro Marques-Vidal, Diane M. Becker, Claude Bouchard, José Haba-Rubio, Georg Homuth, Kurt Lohman, Nora Franceschini, Caizheng Yu, Peter Vollenweider, Ervin F. Fox, Thomas Meitinger, Karen Schwander, Heming Wang, Morris A. Swertz, Aldi T. Kraja, José Eduardo Krieger, Xiuqing Guo, Tangchun Wu, Raymond Noordam, Yongmei Liu, Michael R. Brown, Patrick C.N. Rensen, Annette Peters, Jingmin Liu, Tuomo Rankinen, Robert B. Wallance, Timo A. Lakka, Stephen S. Rich, Yun Ju Sung, Meian He, Till Roenneberg, Wanqing Wen, Dennis O. Mook-Kanamori, M. A. Province, Evangelos Evangelou, L. Adrienne Cupples, Maxime M Bos, Paul S. de Vries, Hans J. Grabe, Lisa R. Yanek, Jiwon Lee, Mario Sims, Bruce M. Psaty, Treva Rice, Tanika N. Kelly, Brenda W.J.H. Penninx, Brigitte Kühnel, Maria E. Graff, Alexandre C. Pereira, Daniel J. Gottlieb, Charles N. Rotimi, Lynne E. Wagenknecht, Ashley van der Spek, Lisa W. Martin, Jeffrey R. O'Connell, Changwei Li, James E. Hixson, Chuan Gao, Alisa K. Manning, Sharon L.R. Kardia, Stella Aslibekyan, Andres Metspalu, Sami Heikkinen, Maris Alver, Xiao-Ou Shu, Amy R. Bentley, Susan Redline, Konstantin Strauch, Tamara B. Harris, Yuri Milaneschi, L.F. Bielak, Marjan Ilkov, Myriam Fornage, Ilja M. Nolte, André G. Uitterlinden, Dina Vojinovic, Hugues Aschard, Paul Elliott, Kent D. Taylor, Najaf Amin, James M. Shikany, Yong-Bing Xiang, Jerome I. Rotter, Vilmundur Gudnason, Cornelia M. van Duijn, Ko Willems van Dijk, Andrea R. V. R. Horimoto, Jonathan Marten, Olli T. Raitakari, Vincent Laville, Pirjo Komulainen, Zhe Wang, Traci M. Bartz, Mary F. Feitosa, Mike A. Nalls, Eric Boerwinkle, Alanna C. Morrison, Melanie Waldenberger, Alexander P. Reiner, Christie M. Ballantyne, Wei Zheng, Raphael Heinzer, M. Arfan Ikram, Colleen M. Sitlani, Lisa de las Fuentes, Patricia B. Munroe, Patricia A. Peyser, Brian E. Cade, Tamar Sofer, Xiaofeng Zhu, Nienke R. Biermasz, Harold Snieder, Elise Lim, Tuomas O. Kilpeläinen, Ching-Ti Liu, Terho Lehtimäki, Thomas W. Winkler, Leo-Pekka Lyytikäinen, Gudny Eiriksdottir, Stephen Sidney, Alan B. Zonderman, Charles Kooperberg, Leiden University Medical Center (LUMC), Universiteit Leiden, Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Universität Regensburg (UR), National Institutes of Health [Bethesda] (NIH), University of Copenhagen = Københavns Universitet (UCPH), Icahn School of Medicine at Mount Sinai [New York] (MSSM), The University of Texas Health Science Center at Houston (UTHealth), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Massachusetts General Hospital [Boston], Harvard T.H. Chan School of Public Health, Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), University of Mississippi Medical Center (UMMC), Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Alabama at Birmingham [ Birmingham] (UAB), University of Washington [Seattle], Universidade de São Paulo Medical School (FMUSP), Icelandic Heart Association [Kopavogur, Iceland] (IHA), University of Michigan [Ann Arbor], University of Michigan System, University of Georgia [USA], School of Public Health [Boston], Boston University [Boston] (BU), Wake Forest University, Pennington Biomedical Research Center, Louisiana State University (LSU), University of Edinburgh, University of Tartu, Imperial College London, University of Ioannina, Huazhong University of Science and Technology [Wuhan] (HUST), Helmholtz Zentrum München = German Research Center for Environmental Health, Fimlab Laboratories [Tampere, Finland], University of Tampere [Finland], Lausanne University Hospital, University of Groningen [Groningen], This project was supported by a grant from the US National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (R01HL118305). This research was supported in part by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. Tuomas O. Kilpeläinen was supported by the Danish Council for Independent Research (DFF–6110-00183) and the Novo Nordisk Foundation (NNF18CC0034900, NNF17OC0026848 and NNF15CC0018486). Diana van Heemst was supported by the European Commission funded project HUMAN (Health-2013-INNOVATION-1-602757). Susan Redline was supported in part by NIH R35HL135818 and HL11338., European Project: 602757,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,HUMAN(2013), Epidemiology, Radiology & Nuclear Medicine, Internal Medicine, Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Digital Health, University of Copenhagen = Københavns Universitet (KU), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Helmholtz-Zentrum München (HZM), Van Duijn, CM, Wang, Heming [0000-0002-1486-7495], Bentley, Amy R [0000-0002-0827-9101], Schwander, Karen [0000-0002-0193-4134], Manning, Alisa [0000-0003-0247-902X], Aschard, Hugues [0000-0002-7554-6783], Richard, Melissa [0000-0003-0129-9860], de Las Fuentes, Lisa [0000-0002-4689-325X], Feitosa, Mary [0000-0002-0933-2410], van der Spek, Ashley [0000-0001-7136-0159], Wang, Zhe [0000-0002-8046-4969], Marten, Jonathan [0000-0001-6916-2014], Laville, Vincent [0000-0003-4946-698X], Evangelou, Evangelos [0000-0002-5488-2999], He, Meian [0000-0002-2096-921X], Lyytikäinen, Leo-Pekka [0000-0002-7200-5455], Marques-Vidal, Pedro [0000-0002-4548-8500], Nolte, Ilja M [0000-0001-5047-4077], Palmer, Nicholette D [0000-0001-8883-2511], Snieder, Harold [0000-0003-1949-2298], Weiss, Stefan [0000-0002-3553-4315], Yanek, Lisa R [0000-0001-7117-1075], Adolfo, Correa [0000-0002-9501-600X], Dimou, Niki [0000-0003-1678-9328], Heikkinen, Sami [0000-0002-6083-2402], Ikram, M Arfan [0000-0003-0372-8585], Krieger, Jose E [0000-0001-5464-1792], Lee, Jiwon [0000-0002-4079-7494], Liu, Jingmin [0000-0003-0001-6013], Martin, Lisa W [0000-0003-4352-0914], Metspalu, Andres [0000-0002-3718-796X], Rensen, Patrick CN [0000-0002-8455-4988], Rich, Stephen S [0000-0003-3872-7793], Rotter, Jerome I [0000-0001-7191-1723], Sofer, Tamar [0000-0001-8520-8860], Taylor, Kent D [0000-0002-2756-4370], Uitterlinden, André G [0000-0002-7276-3387], van Dijk, Ko Willems [0000-0002-2172-7394], Elliott, Paul [0000-0002-7511-5684], Esko, Tõnu [0000-0003-1982-6569], Grabe, Hans J [0000-0003-3684-4208], Zheng, Wei [0000-0003-1226-070X], Bouchard, Claude [0000-0002-0048-491X], Gudnason, Vilmundur [0000-0001-5696-0084], Loos, Ruth JF [0000-0002-8532-5087], Cupples, L Adrienne [0000-0003-0273-7965], Munroe, Patricia B [0000-0002-4176-2947], Liu, Ching-Ti [0000-0002-0703-0742], Apollo - University of Cambridge Repository, Læknadeild (HÍ), Faculty of Medicine (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland, Home Office, Imperial College Healthcare NHS Trust- BRC Funding, Medical Research Council (MRC), and UK DRI Ltd
Subjects: Male, 0301 basic medicine, Epidemiology, General Physics and Astronomy, Genome-wide association study, Genome-wide association studies, Svefnrannsóknir, 0302 clinical medicine, MESH: Aged, 80 and over, Polymorphism (computer science), lcsh:Science, MESH: Phylogeny, Phylogeny, Aged, 80 and over, Genetics, MESH: Aged, [STAT.AP]Statistics [stat]/Applications [stat.AP], Multidisciplinary, MESH: Middle Aged, medicine.diagnostic_test, MESH: Polymorphism, Single Nucleotide, Chromosome Mapping, Middle Aged, Explained variation, Lipids, Sleep in non-human animals, Blóðfita, ddc, 3. Good health, MESH: Young Adult, Female, lipids (amino acids, peptides, and proteins), Erfðarannsóknir, [STAT.ME]Statistics [stat]/Methodology [stat.ME], Adult, Adolescent, MESH: Sleep, Science, Biology, Polymorphism, Single Nucleotide, MESH: Genetic Loci, Article, General Biochemistry, Genetics and Molecular Biology, Young Adult, 03 medical and health sciences, Phylogenetics, Svefn, medicine, Humans, SNP, Dyslipidaemias, Aged, MESH: Adolescent, MESH: Humans, Faraldsfræði, PCSK9, MESH: Adult, General Chemistry, MESH: Lipids, MESH: Male, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Genetic Loci, lcsh:Q, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Sleep, Lipid profile, MESH: Chromosome Mapping, MESH: Female, 030217 neurology & neurosurgery
Abstract: Publisher's version (útgefin grein)., Both short and long sleep are associated with an adverse lipid profile, likely through different biological pathways. To elucidate the biology of sleep-associated adverse lipid profile, we conduct multi-ancestry genome-wide sleep-SNP interaction analyses on three lipid traits (HDL-c, LDL-c and triglycerides). In the total study sample (discovery + replication) of 126,926 individuals from 5 different ancestry groups, when considering either long or short total sleep time interactions in joint analyses, we identify 49 previously unreported lipid loci, and 10 additional previously unreported lipid loci in a restricted sample of European-ancestry cohorts. In addition, we identify new gene-sleep interactions for known lipid loci such as LPL and PCSK9. The previously unreported lipid loci have a modest explained variance in lipid levels: most notable, gene-short-sleep interactions explain 4.25% of the variance in triglyceride level. Collectively, these findings contribute to our understanding of the biological mechanisms involved in sleep-associated adverse lipid profiles., This project was supported by a grant from the US National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (R01HL118305). This research was supported in part by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. Tuomas O. Kilpeläinen was supported by the Danish Council for Independent Research (DFF–6110-00183) and the Novo Nordisk Foundation (NNF18CC0034900, NNF17OC0026848 and NNF15CC0018486). Diana van Heemst was supported by the European Commission funded project HUMAN (Health-2013-INNOVATION-1-602757). Susan Redline was supported in part by NIH R35HL135818 and HL11338. Study-specific acknowledgements can be found in the Supplementary Notes 2 and 4. The data on coronary artery disease have been contributed by the Myocardial Infarction Genetics and CARDIoGRAM investigators, and have been downloaded from www.CARDIOGRAMPLUSC4D.ORG.
Published: 2019

4. Polygenic risk prediction and SNCA haplotype analysis in a Latino Parkinson’s disease cohort

Author: Ignacio F. Mata, Artur F. Schumacher-Schuh, Carlos Velez-Pardo, Gonzalo Arboleda, Emily Mason, Andrea R. V. R. Horimoto, Elif Irem Sarihan, Bruno Lopes Santos-Lobato, Carlos Roberto de Mello Rieder, Dora Yearout, Angel C. Medina, Elison Sarapura-Castro, Pedro Chana-Cuevas, Andrea Rivera-Valdivia, Carlos Cosentino, Timothy D. O’Connor, Sonia Moreno, Víctor Raggio, Cyrus P. Zabetian, Timothy A. Thornton, Vitor Tumas, Mario Cornejo-Olivas, Marlene Jimenez-Del-Rio, Miguel Inca-Martinez, Vanderci Borges, Pilar Mazzetti, Carlos E. Arboleda-Bustos, Douglas Loesch, Francisco Lopera, Luis Torres, Humberto Arboleda, Henrique Ballalai Ferraz, Elena Dieguez, William Fernandez, and Andres G. Lescano
Subjects: Oncology, medicine.medical_specialty, business.industry, Haplotype, Locus (genetics), Genome-wide association study, Disease, Logistic regression, Internal medicine, Cohort, Medicine, 1000 Genomes Project, business, Genetic association
Abstract: BackgroundLarge-scale Parkinson’s disease (PD) genome-wide association studies (GWAS) and meta-analyses have, until recently, only been conducted on subjects with European-ancestry. Consequently, polygenic risk scores (PRS) constructed using PD GWAS data are likely to be less predictive when applied to non-European cohorts.MethodsUsing GWAS data from Nalls et al. 2019, we constructed a PD PRS for a Latino PD cohort (LARGE-PD) and tested it for association with PD status. We validated the PRS performance through testing the PD PRS in an independent cohort of Latino PD patients and by repeating the PRS analysis in LARGE-PD with the addition of 440 external Peruvian controls. To explore the global distribution of PD PRS, we utilized 1000 Genomes Project (1KGP) and Peruvian Genome Project (PGP) data to estimate PD risk allele frequencies. We also tested SNCA haplotypes for association with PD risk using logistic regression in LARGE-PD and a European-ancestry PD cohort from the International Parkinson Disease Genomics Consortium (IPDGC).ResultsThe GWAS-significant PD PRS had an area under the receiver-operator curve (AUC) of 0.668 (95% CI: 0.640-0.695) and explained 2.2% of the phenotypic variance on the liability scale in LARGE-PD. The inclusion of external Peruvian data as controls mitigated this result, dropping the AUC 0.632 (95% CI: 0.607-0.657). In 1KGP Latinos, we found the PD PRS to exhibit a bias by ancestry. At the SNCA locus, haplotypes differ by ancestry. Ancestry-specific SNCA haplotypes were associated with PD status in both LARGE-PD and the IPDGC cohort (p-value < 0.05). Apart from rs356182, these haplotypes share as little as 14% of their variants.ConclusionThe PD PRS has potential for PD risk prediction in Latinos, but variability caused by admixture patterns and bias in the PD PRS calculated using only European-ancestry data limits its utility. The inclusion of diverse subjects can help elucidate PD risk loci and improve risk prediction in non-European cohorts. In the case of the SNCA locus, by leveraging a Latino cohort, we provide orthogonal evidence for rs356182 causality.
Published: 2021

5. Admixture mapping reveals the association between Native American ancestry at 3q13.11 and reduced risk of Alzheimer’s disease in Caribbean Hispanics

Author: Diane Xue, Elizabeth E. Blue, Timothy A. Thornton, and Andrea R. V. R. Horimoto
Subjects: 0301 basic medicine, Cognitive Neuroscience, Genetic genealogy, Population, Genetic admixture, Neurosciences. Biological psychiatry. Neuropsychiatry, Biology, Polymorphism, Single Nucleotide, White People, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, Admixture mapping, Genetic architecture, Humans, Genetic Predisposition to Disease, RC346-429, education, American Indian or Alaska Native, ALCAM, Genetics, Multi-omics, education.field_of_study, Research, Haplotype, Local ancestry, Hispanic or Latino, Heritability, 030104 developmental biology, Caribbean Region, Neurology, Neurology. Diseases of the nervous system, Chromosomes, Human, Pair 3, Neurology (clinical), CBLB, Genome scan, Alzheimer’s disease, 030217 neurology & neurosurgery, RC321-571, Genome-Wide Association Study
Abstract: Background Genetic studies have primarily been conducted in European ancestry populations, identifying dozens of loci associated with late-onset Alzheimer’s disease (AD). However, much of AD’s heritability remains unexplained; as the prevalence of AD varies across populations, the genetic architecture of the disease may also vary by population with the presence of novel variants or loci. Methods We conducted genome-wide analyses of AD in a sample of 2565 Caribbean Hispanics to better understand the genetic contribution to AD in this population. Statistical analysis included both admixture mapping and association testing. Evidence for differential gene expression within regions of interest was collected from independent transcriptomic studies comparing AD cases and controls in samples with primarily European ancestry. Results Our genome-wide association study of AD identified no loci reaching genome-wide significance. However, a genome-wide admixture mapping analysis that tests for association between a haplotype’s ancestral origin and AD status detected a genome-wide significant association with chromosome 3q13.11 (103.7–107.7Mb, P = 8.76E−07), driven by a protective effect conferred by the Native American ancestry (OR = 0.58, 95%CI = 0.47−0.73). Within this region, two variants were significantly associated with AD after accounting for the number of independent tests (rs12494162, P = 2.33E−06; rs1731642, P = 6.36E−05). The significant admixture mapping signal is composed of 15 haplotype blocks spanning 5 protein-coding genes (ALCAM, BBX, CBLB, CCDC54, CD47) and four brain-derived topologically associated domains, and includes markers significantly associated with the expression of ALCAM, BBX, CBLB, and CD47 in the brain. ALCAM and BBX were also significantly differentially expressed in the brain between AD cases and controls with European ancestry. Conclusion These results provide multiethnic evidence for a relationship between AD and multiple genes at 3q13.11 and illustrate the utility of leveraging genetic ancestry diversity via admixture mapping for new insights into AD.
Published: 2021

6. Characterizing the Genetic Architecture of Parkinson's Disease in Latinos

Author: Carlos E. Arboleda-Bustos, Douglas Loesch, Paul Cannon, Francisco Lopera, Carlos Cosentino, Andrea Rivera-Valdivia, Carlos Velez-Pardo, Cyrus P. Zabetian, Mario Cornejo-Olivas, Ignacio F. Mata, Sonia Moreno, Karl Heilbron, Carlos Roberto de Mello Rieder, Miguel Inca-Martinez, Andrea R. V. R. Horimoto, Pilar Mazzetti, Luis Torres, Vanderci Borges, Dora Yearout, Elison Sarapura-Castro, Gonzalo Arboleda, Timothy D. O’Connor, Artur F. Schumacher-Schuh, Elif Irem Sarihan, Bruno Lopes Santos-Lobato, Vitor Tumas, Marlene Jimenez-Del-Rio, Pedro Chana-Cuevas, William Fernandez, Emily Mason, Andres G. Lescano, Humberto Arboleda, Elena Dieguez, Henrique Ballalai Ferraz, Angel C. Medina, Timothy A. Thornton, and Víctor Raggio
Subjects: Adult, Male, Genetic admixture, Genome-wide association study, Locus (genetics), Disease, Biology, Polymorphism, Single Nucleotide, Article, Cohort Studies, Humans, Genetic Predisposition to Disease, Latinos, Allele, Aged, Genetics, Parkinson's Disease, Genetic Variation, Parkinson Disease, Hispanic or Latino, Middle Aged, South America, Genetic architecture, Neurology, Genetic Loci, Cohort, Etiology, Female, Neurology (clinical), Genetic Architecture, Genome-Wide Association Study
Abstract: OBJECTIVE This work was undertaken in order to identify Parkinson's disease (PD) risk variants in a Latino cohort, to describe the overlap in the genetic architecture of PD in Latinos compared to European-ancestry subjects, and to increase the diversity in PD genome-wide association (GWAS) data. METHODS We genotyped and imputed 1,497 PD cases and controls recruited from nine clinical sites across South America. We performed a GWAS using logistic mixed models; variants with a p-value
Published: 2021

7. Ancestral diversity improves discovery and fine-mapping of genetic loci for anthropometric traits - the Hispanic/Latino Anthropometry Consortium

Author: Heather M. Highland, Francisco Rothhammer, Kristin L. Young, Andres Ruiz-Linares, Yujie Wang, Roberta McKean-Cowdin, Fernando Pires Hartwig, Noël P. Burtt, Ye Feng, Mark O. Goodarzi, Adrienne M. Stilp, Andrea R. V. R. Horimoto, Charleston W. K. Chiang, Michael Preuss, Adam G. Lilly, Gabriela Torres-Mejía, V. Saroja Voruganti, Donna E. Lehman, LáShauntá M. Glover, Roelof A.J. Smit, Yii-Der Ida Chen, Carl Langfeld, Xiuqing Guo, Rebecca Rohde, Estela Blanco, Samuel Canizales-Quinteros, Ravindranath Duggirala, Tamar Sofer, Sheila Gahagan, Anny H. Xiang, Ruth J. F. Loos, Hung-Hsin Chen, Sobha Puppala, Giovanni Poletti, Yang Hai, Claudia Schumann, Victor Acuña-Alonzo, Sharon G. Adler, Kari E. North, José Eduardo Krieger, Xinruo Zhang, Christopher A. Haiman, Alexandre C. Pereira, Thomas A. Buchanan, Xiaoyi Raymond Gao, Matthew A. Allison, Zorayr Arzumanyan, Jennifer A. Smith, Jie Yao, Marta Guindo-Martínez, Carmen R. Isasi, Clicerio González-Villalpando, Anthony G. Commuzzie, Nancy J. Cox, Kent D. Taylor, Victoria L. Buchanan, Carla Gallo, Esther M. John, Humberto García-Ortiz, David V. Conti, Lynne E. Wagenknecht, Carlos A. Aguilar-Salinas, Jose C. Florez, Willa A. Hsueh, Craig L. Hanis, Susanne B. Nicholas, Struan F.A. Grant, José de Jesús Peralta Romero, Lindsay Fernández-Rhodes, Alvin G. Thomas, Jerome I. Rotter, Maria Cátira Bortolini, Anne E. Justice, Hakon Hakonarson, Darryl Nousome, Nicholette Allred, Leslie J. Raffel, Nancy F. Butte, Wanying Zhu, Joanne E. Curran, Miguel Cruz, Xiaohui Li, Kevin Sandow, Minhui Chen, Poojan Shrestha, Eli Ipp, Teresa Tusie, Minjung Kho, Bernando Horta, Kelvin Lam, Stephanie M. Gogarten, Pauline Genter, John Blangero, Robert P. Igo, Mariaelisa Graff, Rolando González-José, Kaye Roll, Shelley A. Cole, Josep M. Mercader, Jingyi Tan, Esteban J. Parra, Jennifer E. Below, Sudha K. Iyengar, Qibin Qi, Elad Ziv, Gabriel Bedoya, Sara Pulit, Lorena Orozco, Fouad Kandeel, Astride Audirac-Chalifour, Laura Fejerman, Jerry L. Nadler, Daeeun Kim, Kaustubh Adhikari, George Papnicolaou, and Jonathan P. Bradfield
Subjects: Linkage disequilibrium, medicine, Locus (genetics), Genome-wide association study, Anthropometry, Overweight, medicine.symptom, Biology, Population stratification, Body mass index, Demography, Genetic association
Abstract: Hispanic/Latinos have been underrepresented in genome-wide association studies (GWAS) for anthropometric traits despite notable anthropometric variability with ancestry proportions, and a high burden of growth stunting and overweight/obesity in Hispanic/Latino populations. This address this knowledge gap, we analyzed densely-imputed genetic data in a sample of Hispanic/Latino adults, to identify and fine-map common genetic variants associated with body mass index (BMI), height, and BMI-adjusted waist-to-hip ratio (WHRadjBMI). We conducted a GWAS of 18 studies/consortia as part of the Hispanic/Latino Anthropometry (HISLA) Consortium (Stage 1, n=59,769) and validated our findings in 9 additional studies (HISLA Stage 2, n=9,336). We conducted a trans-ethnic GWAS with summary statistics from HISLA Stage 1 and existing consortia of European and African ancestries. In our HISLA Stage 1+2 analyses, we discovered one novel BMI locus, as well two novel BMI signals and another novel height signal, each within established anthropometric loci. In our trans-ethnic meta- analysis, we identified three additional novel BMI loci, one novel height locus, and one novel WHRadjBMI locus. We also identified three secondary signals for BMI, 28 for height, and two for WHRadjBMI. We replicated >60 established anthropometric loci in Hispanic/Latino populations at genome-wide significance—representing up to 30% of previously-reported index SNP anthropometric associations. Trans-ethnic meta-analysis of the three ancestries showed a small-to-moderate impact of uncorrected population stratification on the resulting effect size estimates. Our novel findings demonstrate that future studies may also benefit from leveraging differences in linkage disequilibrium patterns to discover novel loci and additional signals with less residual population stratification.
Published: 2021

8. Genome-Wide Admixture Mapping of Estimated Glomerular Filtration Rate and Chronic Kidney Disease Identifies European and African Ancestry-of-Origin Loci in Hispanic and Latino Individuals in the United States

Author: Nora Franceschini, Martha L. Daviglus, Diane Xue, Timothy A. Thornton, Jainwen Cai, Andrea R. V. R. Horimoto, and James P. Lash
Subjects: Adult, Male, Genetic genealogy, Genetic admixture, Black People, Locus (genetics), Biology, Genome, White People, Chromosome 15, Gene mapping, Up Front Matters, medicine, Humans, Renal Insufficiency, Chronic, Genetics, Chromosome, Chromosome Mapping, General Medicine, Hispanic or Latino, Middle Aged, medicine.disease, United States, Black or African American, Basic Research, Nephrology, Genetic Loci, Female, Kidney disease, Genome-Wide Association Study, Glomerular Filtration Rate
Abstract: Background Admixture mapping is a powerful approach for gene mapping of complex traits that leverages the diverse genetic ancestry in populations with recent admixture, such as Hispanic or Latino individuals in the United States. These individuals have an increased risk of chronic kidney disease (CKD). Methods We performed genome-wide admixture mapping for both CKD and estimated glomerular filtration rate (eGFR) in a sample of 12,601 participants from the Hispanic Community Health Study/Study of Latinos, with validation in a sample of 8191 African American participants from the Women's Health Initiative (WHI). We also compared the findings with those from a conventional genome-wide association study. Results Three novel ancestry-of-origin loci were identified on chromosomes 2, 14, and 15 for CKD and eGFR-loci harboring genes that have been implicated in kidney function. The chromosome 2 locus comprises two European ancestry regions encompassing the FSHR and NRXN1 genes, with European ancestry at this locus associated with increased CKD risk. The chromosome 14 locus, found within the DLK1-DIO3 imprinted domain, was associated with lower eGFR and driven by European ancestry. The eGFR-associated locus on chromosome 15 included intronic variants of RYR3 and was within an African-specific genomic region associated with higher eGFR. The genomewide association study failed to identify significant associations in these regions. We validated the chromosome 14 and 15 loci associated with eGFR in the WHI African American participants. Conclusions This study provides evidence of shared ancestry-specific genomic regions influencing eGFR in Hispanic or Latino individuals and African American individuals, and illustrates the potential for leveraging genetic ancestry in recently admixed populations for the discovery of novel candidate loci for kidney phenotypes.
Published: 2021

9. Genome-wide admixture mapping of eGFR and CKD identify European and African ancestry-of-origin loci in U.S. Hispanics/Latinos

Author: Jainwen Cai, Nora Franceschini, Andrea R. V. R. Horimoto, Timothy A. Thornton, Martha L. Daviglus, and James P. Lash
Subjects: Genetics, Chromosome 15, Gene mapping, Genetic genealogy, Chromosome, Genetic admixture, Locus (genetics), Biology, Genome, Gene
Abstract: BackgroundAdmixture mapping is a powerful approach for gene mapping of complex traits that leverages the diverse genetic ancestry in populations with recent admixture such as U.S. Hispanics/Latinos (HL), who have increased risk of chronic kidney disease (CKD).MethodsGenome-wide admixture mapping was performed for CKD and estimated glomerular filtration rate (eGFR) in a sample of 12,601 participants from the Hispanic Community Health Study/Study of Latinos, with validation in a sample of 8191 African Americans from the Women’s Health Initiative (WHI).ResultsThree novel ancestry-of-origin loci were identified on chromosomes 2, 14 and 15 for CKD and eGFR. The chromosome 2 locus (2p16.3) consisted of two European ancestry regions encompassing the FSHR and NRXN1 genes, with European ancestry at this locus associated with increased risk for CKD. The chromosome 14 locus (14q32.2) located within the DLK1-DIO3 imprinted domain was driven by European ancestry, and was associated with lower eGFR. The chromosome 15 locus (15q13.3-14) included intronic variants of RYR3 and was within an African-specific genomic region that was associated with higher eGFR. These findings were compared to the conventional genome-wide association study that failed to identify significant associations in these regions. We validated the chromosome 14 and 15 loci for eGFR in the WHI African Americans.ConclusionsThis study provides evidence of shared ancestry-specific genomic regions influencing eGFR in HL and African Americans, and illustrates the potential for leveraging genetic ancestry in recently admixed populations for novel discovery of kidney trait loci.
Published: 2021

10. Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions

Author: Alexandre C. Pereira, Jie Yao, Makoto Hirata, Ozren Polasek, Dragana Vuckovic, Mariaelisa Graff, Jing Hua Zhao, Michael R. Brown, Xuan Deng, Barbara V. Howard, Vilmundur Gudnason, Tuomo Rankinen, Yuan Shi, Timo A. Lakka, Ulrich Broeckel, Anuradhani Kasturiratne, Eric Boerwinkle, Charles Kooperberg, Hugues Aschard, Stephen S. Rich, Pamela J. Schreiner, Dan E. Arking, Hans J. Grabe, Ilaria Gandin, Mario Sims, Carl D. Langefeld, Yii-Der Ida Chen, Meian He, W. James Gauderman, Bruce M. Psaty, Kent D. Taylor, Tõnu Esko, Olli T. Raitakari, Saima Afaq, Maik Pietzner, Federica Laguzzi, Dennis O. Mook-Kanamori, Gregory P. Wilson, Xiuqing Guo, Jaspal S. Kooner, David R. Jacobs, Yajuan Wang, Raha Pazoki, Wei Zhao, Andres Metspalu, Mary F. Feitosa, Jost B. Jonas, Tin Aung, Tamara B. Harris, Karin Leander, Nancy L. Pedersen, Charles B. Eaton, Sharon L.R. Kardia, Bernardo L. Horta, Candace M. Kammerer, Terrence Forrester, Alexander P. Reiner, Paul W. Franks, Tanika N. Kelly, Igor Rudan, Ruben N. Eppinga, Melissa A. Richard, Colin A. McKenzie, Christine Williams, Christian Gieger, Joseph H. Lee, Brigitte Kühnel, Christopher P. Nelson, Wen Bin Wei, Antonietta Robino, Anne U. Jackson, E. Shyong Tai, Alisa K. Manning, Lisa R. Yanek, Paul Elliott, Lynne E. Wagenknecht, Ananda R. Wickremasinghe, José Eduardo Krieger, Peter S. Sever, Nora Franceschini, André G. Uitterlinden, Paul M. Ridker, Yun J. Sung, Karen L. Mohlke, Thomas H. Mosley, Nilesh J. Samani, Patricia B. Munroe, Jennifer A. Smith, John M. C. Connell, H. Janaka de Silva, Nicholas Y. Q. Tan, Jian'an Luan, Jennifer E. Huffman, Anna F. Dominiczak, Carsten Oliver Schmidt, Christie M. Ballantyne, Peter J. van der Most, Anuj Goel, Jerome I. Rotter, Amy R. Bentley, Lihua Wang, Rajkumar Dorajoo, Lenore J. Launer, Yechiel Friedlander, Mickaël Canouil, Traci M. Bartz, Thomas Meitinger, Robert A. Scott, Mike A. Nalls, Xueling Sim, Sarah E. Harris, Michael A. Province, Chew-Kiat Heng, Zhe Wang, Norihiro Kato, Evangelos Evangelou, Philippe Froguel, Virginia Fisher, Leslie J. Raffel, Renée de Mutsert, Michele K. Evans, Brenda W.J.H. Penninx, Yih Chung Tham, Tin Louie, Nana Matoba, Lawrence F. Bielak, Andrea R. V. R. Horimoto, Jingmin Liu, Lynda M. Rose, Nona Sotoodehnia, Daniel I. Chasman, Jasmin Divers, John M. Starr, Patricia A. Peyser, Ervin R. Fox, Barry I. Freedman, Megan L. Grove, Jeffrey R. O'Connell, Rob M. van Dam, Michiaki Kubo, Jessica D. Faul, Fang-Chi Hsu, Yize Li, Ilja M. Nolte, Caroline Hayward, Paolo Gasparini, Chiea Chuen Khor, Changwei Li, Xu Chen, James E. Hixson, Patrik K. E. Magnusson, John C. Chambers, Yoichiro Kamatani, Sami Heikkinen, M. Abdullah Said, Martin Farrall, Alena Stančáková, Konstantin Strauch, Albert V. Smith, Yik Ying Teo, Bamidele O. Tayo, Tamar Sofer, Caizheng Yu, Maris Alver, Oscar H. Franco, Yongmei Liu, Ioanna Ntalla, Myriam Fornage, W. Craig Johnson, Dina Vojinovic, William R. Scott, David R. Weir, Yanick Hagemeijer, Raymond Noordam, Mathilde Boissel, Cornelia M. van Duijn, Karen Schwander, Jingzhong Ding, James Scott, Diana van Heemst, Ching-Yu Cheng, Woon-Puay Koh, Jianjun Liu, Kenneth J. Mukamal, Blair H. Smith, Claude Bouchard, Claudia Langenberg, Jingjing Liang, Wei Zheng, Najaf Amin, Ulf de Faire, Bing Yu, Archie Campbell, Kari E. North, Salman M. Tajuddin, Fernando Pires Hartwig, Steve B. Kritchevsky, Tibor V. Varga, Pirjo Komulainen, Hugh Watkins, Johanna Kuusisto, Kurt Lohman, Rozenn N. Lemaitre, Ani Manichaikul, Dabeeru C. Rao, Kenneth Rice, Weihua Zhang, Franco Giulianini, Reedik Mägi, Solomon K. Musani, Wanqing Wen, Nicholas J. Wareham, Charles N. Rotimi, Marzyeh Amini, Rainer Rauramaa, Nicholette D. Palmer, Annette Peters, Neil R Poulter, Benjamin Lehne, Matthias Nauck, Harold Snieder, Donald W. Bowden, M. Arfan Ikram, Lisa de las Fuentes, C. Charles Gu, Xiaofeng Zhu, Markku Laakso, Tuomas O. Kilpeläinen, Ching-Ti Liu, Michael Boehnke, Jin-Fang Chai, Lili Milani, L. Adrienne Cupples, Yuri Milaneschi, Kiang Liu, Stephen Sidney, Alan B. Zonderman, Thomas W. Winkler, Ian J. Deary, Fumihiko Takeuchi, Mary K. Wojczynski, Pim van der Harst, Leo-Pekka Lyytikäinen, Jennifer G. Robinson, Chuan Gao, Xiao-Ou Shu, Diane M. Becker, Mohsen Ghanbari, Alanna C. Morrison, Jian-Min Yuan, Tomohiro Katsuya, Ivana Kolcic, Melanie Waldenberger, Terho Lehtimäki, Heikki A. Koistinen, Erin B. Ware, Ya Xing Wang, Marie Loh, Treva Rice, Qing Duan, Aldi T. Kraja, Sabanayagam Charumathi, Tien Yin Wong, Paul S. de Vries, Yujie Wang, Muhammad Riaz, Home Office, Action on Hearing Loss, Imperial College Healthcare NHS Trust- BRC Funding, British Heart Foundation, Medical Research Council (MRC), Wellcome Trust, National Institute for Health Research, Luan, Jian'an [0000-0003-3137-6337], Pietzner, Maik [0000-0003-3437-9963], Zhao, Jing Hua [0000-0003-4930-3582], Langenberg, Claudia [0000-0002-5017-7344], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, APH - Mental Health, Psychiatry, APH - Digital Health, The University of Texas Health Science Center at Houston (UTHealth), National Institutes of Health [Bethesda] (NIH), Washington University in Saint Louis (WUSTL), University of Regensburg, Queen Mary University of London (QMUL), Washington University School of Medicine in St. Louis, Harbor UCLA Medical Center [Torrance, Ca.], University of North Carolina at Chapel Hill (UNC), Singapore National Eye Centre and Duke-NUS [Singapore], Singapore Eye Research Institute [Singapore] (SERI), National University of Singapore (NUS), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Département de Biologie Computationnelle - Department of Computational Biology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), University Management, Department of Medicine, University of Helsinki, Endokrinologian yksikkö, HUS Abdominal Center, Lifelines Cohort, Groningen, The Netherlands (Lifelines Cohort Study), Epidemiology, Neurology, Radiology & Nuclear Medicine, Internal Medicine, Life Course Epidemiology (LCE), Cardiovascular Centre (CVC), de Vries, Paul S, Brown, Michael R, Bentley, Amy R, Sung, Yun J, Winkler, Thomas W, Ntalla, Ioanna, Schwander, Karen, Kraja, Aldi T, Guo, Xiuqing, Franceschini, Nora, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Huffman, Jennifer E, Musani, Solomon K, Li, Changwei, Feitosa, Mary F, Richard, Melissa A, Noordam, Raymond, Aschard, Hugue, Bartz, Traci M, Bielak, Lawrence F, Deng, Xuan, Dorajoo, Rajkumar, Lohman, Kurt K, Manning, Alisa K, Rankinen, Tuomo, Smith, Albert V, Tajuddin, Salman M, Evangelou, Evangelo, Graff, Mariaelisa, Alver, Mari, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gandin, Ilaria, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E, Hartwig, Fernando P, He, Meian, Horimoto, Andrea R V R, Hsu, Fang-Chi, Jackson, Anne U, Kasturiratne, Anuradhani, Komulainen, Pirjo, Kühnel, Brigitte, Laguzzi, Federica, Lee, Joseph H, Luan, Jian'An, Lyytikäinen, Leo-Pekka, Matoba, Nana, Nolte, Ilja M, Pietzner, Maik, Riaz, Muhammad, Said, M Abdullah, Scott, Robert A, Sofer, Tamar, Stancáková, Alena, Takeuchi, Fumihiko, Tayo, Bamidele O, van der Most, Peter J, Varga, Tibor V, Wang, Yajuan, Ware, Erin B, Wen, Wanqing, Yanek, Lisa R, Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Amin, Najaf, Amini, Marzyeh, Arking, Dan E, Aung, Tin, Ballantyne, Christie, Boerwinkle, Eric, Broeckel, Ulrich, Campbell, Archie, Canouil, Mickaël, Charumathi, Sabanayagam, Chen, Yii-Der Ida, Connell, John M, de Faire, Ulf, de Las Fuentes, Lisa, de Mutsert, Renée, de Silva, H Janaka, Ding, Jingzhong, Dominiczak, Anna F, Duan, Qing, Eaton, Charles B, Eppinga, Ruben N, Faul, Jessica D, Fisher, Virginia, Forrester, Terrence, Franco, Oscar H, Friedlander, Yechiel, Ghanbari, Mohsen, Giulianini, Franco, Grabe, Hans J, Grove, Megan L, Gu, C Charle, Harris, Tamara B, Heikkinen, Sami, Heng, Chew-Kiat, Hirata, Makoto, Hixson, James E, Howard, Barbara V, Ikram, M Arfan, Jacobs, David R, Johnson, Craig, Jonas, Jost Bruno, Kammerer, Candace M, Katsuya, Tomohiro, Khor, Chiea Chuen, Kilpeläinen, Tuomas O, Koh, Woon-Puay, Koistinen, Heikki A, Kolcic, Ivana, Kooperberg, Charle, Krieger, Jose E, Kritchevsky, Steve B, Kubo, Michiaki, Kuusisto, Johanna, Lakka, Timo A, Langefeld, Carl D, Langenberg, Claudia, Launer, Lenore J, Lehne, Benjamin, Lemaitre, Rozenn N, Li, Yize, Liang, Jingjing, Liu, Jianjun, Liu, Kiang, Loh, Marie, Louie, Tin, Mägi, Reedik, Manichaikul, Ani W, Mckenzie, Colin A, Meitinger, Thoma, Metspalu, Andre, Milaneschi, Yuri, Milani, Lili, Mohlke, Karen L, Mosley, Thomas H, Mukamal, Kenneth J, Nalls, Mike A, Nauck, Matthia, Nelson, Christopher P, Sotoodehnia, Nona, O'Connell, Jeff R, Palmer, Nicholette D, Pazoki, Raha, Pedersen, Nancy L, Peters, Annette, Peyser, Patricia A, Polasek, Ozren, Poulter, Neil, Raffel, Leslie J, Raitakari, Olli T, Reiner, Alex P, Rice, Treva K, Rich, Stephen S, Robino, Antonietta, Robinson, Jennifer G, Rose, Lynda M, Rudan, Igor, Schmidt, Carsten O, Schreiner, Pamela J, Scott, William R, Sever, Peter, Shi, Yuan, Sidney, Stephen, Sims, Mario, Smith, Blair H, Smith, Jennifer A, Snieder, Harold, Starr, John M, Strauch, Konstantin, Tan, Nichola, Taylor, Kent D, Teo, Yik Ying, Tham, Yih Chung, Uitterlinden, André G, van Heemst, Diana, Vuckovic, Dragana, Waldenberger, Melanie, Wang, Lihua, Wang, Yujie, Wang, Zhe, Wei, Wen Bin, Williams, Christine, Wilson, Gregory, Wojczynski, Mary K, Yao, Jie, Yu, Bing, Yu, Caizheng, Yuan, Jian-Min, Zhao, Wei, Zonderman, Alan B, Becker, Diane M, Boehnke, Michael, Bowden, Donald W, Chambers, John C, Deary, Ian J, Esko, Tõnu, Farrall, Martin, Franks, Paul W, Freedman, Barry I, Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Horta, Bernardo L, Kamatani, Yoichiro, Kato, Norihiro, Kooner, Jaspal S, Laakso, Markku, Leander, Karin, Lehtimäki, Terho, Magnusson, Patrik K E, Penninx, Brenda, Pereira, Alexandre C, Rauramaa, Rainer, Samani, Nilesh J, Scott, Jame, Shu, Xiao-Ou, van der Harst, Pim, Wagenknecht, Lynne E, Wang, Ya Xing, Wareham, Nicholas J, Watkins, Hugh, Weir, David R, Wickremasinghe, Ananda R, Zheng, Wei, Elliott, Paul, North, Kari E, Bouchard, Claude, Evans, Michele K, Gudnason, Vilmundur, Liu, Ching-Ti, Liu, Yongmei, Psaty, Bruce M, Ridker, Paul M, van Dam, Rob M, Kardia, Sharon L R, Zhu, Xiaofeng, Rotimi, Charles N, Mook-Kanamori, Dennis O, Fornage, Myriam, Kelly, Tanika N, Fox, Ervin R, Hayward, Caroline, van Duijn, Cornelia M, Tai, E Shyong, Wong, Tien Yin, Liu, Jingmin, Rotter, Jerome I, Gauderman, W Jame, Province, Michael A, Munroe, Patricia B, Rice, Kenneth, Chasman, Daniel I, Cupples, L Adrienne, Rao, Dabeeru C, Morrison, Alanna C, and Academic Medical Center
Subjects: Male, Epidemiology, Genome-wide association study, Cardiovascular, MESH: Genotype, Substance Misuse, Alcohol Use and Health, 0302 clinical medicine, Aetiology, triglycerides, 11 Medical and Health Sciences, Public, Environmental & Occupational Health, [STAT.AP]Statistics [stat]/Applications [stat.AP], MESH: Middle Aged, MESH: Life Style, genome wide, gene-alcohol interaction, lipid levels, Lipid Measurement, Lifelines Cohort, DENSITY-LIPOPROTEIN CHOLESTEROL, MESH: Young Adult, 030220 oncology & carcinogenesis, Kexin, LOW-FREQUENCY, MESH: Cholesterol, HDL, MESH: Cholesterol, LDL, MESH: Triglycerides, HDL, Alcohol Drinking, Genotype, alcohol consumption, MESH: Phenotype, LDL, lipids, 03 medical and health sciences, Genetics, Humans, Life Style, METAANALYSIS, 01 Mathematical Sciences, Aged, MESH: Adolescent, HDL CHOLESTEROL, MESH: Humans, Science & Technology, Cholesterol, APOBEC1, Lifelines Cohort, Groningen, The Netherlands (Lifelines Cohort Study), MESH: Vascular Endothelial Growth Factor B, Racial Groups, cholesterol, The Netherlands, MESH: Adult, CONSUMPTION, chemistry, MESH: Genome-Wide Association Study, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Lipid profile, MESH: Female, MESH: Alcohol Drinking, MESH: Continental Population Groups, Vascular Endothelial Growth Factor B, Original Contributions, Blood lipids, VEGF-B, Medical and Health Sciences, Mathematical Sciences, BLOOD-LIPIDS, chemistry.chemical_compound, 2.1 Biological and endogenous factors, 030212 general & internal medicine, MESH: Aged, medicine.diagnostic_test, PLASMA, gene-environment interactions, Middle Aged, 3142 Public health care science, environmental and occupational health, Alcoholism, Phenotype, Female, gene-lifestyle interactions, genome-wide association studies, [STAT.ME]Statistics [stat]/Methodology [stat.ME], Life Sciences & Biomedicine, Groningen, Adult, Adolescent, Biology, Young Adult, medicine, CORONARY-HEART-DISEASE, Human Genome, Cholesterol, HDL, Lipid metabolism, Cholesterol, LDL, InterAct Consortium, MESH: Lipids, MESH: Male, INDIVIDUALS, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Genome-Wide Association Study
Abstract: © The Author(s) 2019. A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-Alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2- degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 × 10?6) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 × 10?8 using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models. National Heart, Lung, and Blood Institute; American Heart Association Grant
Published: 2019

11. Impact of common cardio-metabolic risk factors on fatal and non-fatal cardiovascular disease in Latin America and the Caribbean: an individual-level pooled analysis of 31 cohort studies

Author: José Boggia, Alvaro Cc Maciel, Pablo Perel, Marselle B Amadio, Flávio Danni Fuchs, Jorge Tartaglione, Carla Do Bernardo, João Luiz Bastos, Jorge Salmerón, Claudia Bambs, Karen Oppermann, Gilbert Brenes-Camacho, J. Jaime Miranda, Poli Mara Spritzer, Nohora I Rodriguez, Oscar Muñoz, Pollyanna Kássia de Oliveira Borges, Edward W. Gregg, Laura Gutierrez, Ramon A Sanchez, Walter G Espeche, Paula Ramírez-Palacios, Rodrigo M. Carrillo-Larco, Juan E. Blümel, Nelson A S Silva, Marco Aurélio Peres, Leila Beltrami Moreira, Martin Lajous, Clicerio González-Villalpando, Eleonora d'Orsi, Karina Mary de Paiva, Sérgio Viana Peixoto, Alexandre C. Pereira, Majid Ezzati, Betty S Manrique-Espinoza, Miguel Bravo, Ramón Álvarez-Vaz, Maria S. Castillo Rascon, Suely Ga Gimeno, Luis Rosero-Bixby, Rosalba Rojas-Martínez, Elard Koch, Ricardo Oliveira Guerra, Dalia Stern, Anselm Hennis, Vilma Irazola, Aaron Salinas-Rodriguez, Catterina Ferreccio, Carlos A. Aguilar-Salinas, Paulo A. Lotufo, Blanca H. Ceballos, Goodarz Danaei, Cassiano Ricardo Rech, Donaji Gomez-Velasco, Adrian Cortes-Valencia, Thiago L N Silva, Andrea R. V. R. Horimoto, Adolfo Rubinstein, Mariachiara Di Cesare, Cecilia Baccino, Roberto de Sa Cunha, Liam Smeeth, Verônica Colpani, Sandra C. Fuchs, Maria Fernanda Lima-Costa, Larissa Pruner Marques, Ruy Lopez-Ridaura, Gonzalo Grazioli, Horacio A Carbajal, Andrea Huidobro, Sandra Cortés, Karen Glazer Peres, Berenice Rivera-Paredez, Antonio Bernabe-Ortiz, Martin R Salazar, Álvaro Ruiz-Morales, José Geraldo Mill, Ian Hambleton, María-Elena González-Villalpando, Gloria L. Beckles, William H. Dow, Fiorella Tartaglione, David Alejandro González-Chica, Jackie A. Cooper, Rafael Velázquez-Cruz, Katia Vergetti Bloch, Lariane M Ono, Fernando Luiz Herkenhoff, and Wellcome Trust
Subjects: business.industry, Regression dilution, Disease, Blood pressure, Relative risk, Medicine, Public aspects of medicine, RA1-1270, Risk factor, business, Body mass index, Disease burden, Cohort study, Demography, Research Paper
Abstract: Background: Estimates of the burden of cardio-metabolic risk factors in Latin America and the Caribbean (LAC) rely on relative risks (RRs) from non-LAC countries. Whether these RRs apply to LAC remains unknown. Methods: We pooled LAC cohorts. We estimated RRs per unit of exposure to body mass index (BMI), systolic blood pressure (SBP), fasting plasma glucose (FPG), total cholesterol (TC) and non-HDL cholesterol on fatal (31 cohorts, n=168,287) and non-fatal (13 cohorts, n=27,554) cardiovascular diseases, adjusting for regression dilution bias. We used these RRs and national data on mean risk factor levels to estimate the number of cardiovascular deaths attributable to non-optimal levels of each risk factor. Results: Our RRs for SBP, FPG and TC were like those observed in cohorts conducted in high-income countries; however, for BMI, our RRs were consistently smaller in people below 75 years of age. Across risk factors, we observed smaller RRs among older ages. Non-optimal SBP was responsible for the largest number of attributable cardiovascular deaths ranging from 38 per 100,000 women and 54 men in Peru, to 261 (Dominica, women) and 282 (Guyana, men). For non-HDL cholesterol, the lowest attributable rate was for women in Peru (21) and men in Guatemala (25), and the largest in men (158) and women (142) from Guyana. Interpretation: RRs for BMI from studies conducted in high-income countries may overestimate disease burden metrics in LAC; conversely, RRs for SBP, FPG and TC from LAC cohorts are similar to those estimated from cohorts in high-income countries. Funding: Wellcome Trust (214185/Z/18/Z)
Published: 2021

12. Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight

Author: Maryam Sharafkhah, Emanuel Zitt, Majid Ezzati, Luxia Zhang, Young-Ho Khang, Ellina Rakhimova, Kairit Mikkel, Tiina Vlasoff, Eruke E. Egbagbe, Sidsel Graff-Iversen, Ilona Nenko, Magdalena Klimek, Mathilde Savy, Sanjib Kumar Sharma, Alfonso Siani, Luís Lopes, Vanina Bongard, Gregor Jurak, Jacqueline F. Price, Christina-Paulina Lambrinou, Maria Lc Iurilli, Rainford J. Wilks, Bontha V. Babu, Fereidoun Azizi, Harunobu Nakamura, Marialaura Bonaccio, Angela Döring, Zhenyu Zhang, Naser Ahmadi, Jolanta Słowikowska-Hilczer, Ana Paula Carlos Cândido, Clive Osmond, Thirunavukkarasu Sathish, Robert J. Adams, Themistoklis Tzotzas, Reina Engle-Stone, Atul Trivedi, Shoichiro Tsugane, Niels Møller, Jorge Bezerra, Dénes Molnár, Muhammad Fadhli Mohd Yusoff, Badreya Al-Lahou, J. Jaime Miranda, Bahram Mohajer, Sigmund A. Anderssen, Lital Keinan Boker, Eero Kajantie, Martin Gulliford, Maties Torrent, Sumit Bharadwaj, Toshiharu Ninomiya, Zbigniew Gaciong, Nayu Ikeda, Li Juan Wu, Adrian Richter, Licia Iacoviello, Marc J. Gunter, Wenbin Wei, Norsyamlina Che Abdul Rahim, Eman Aly, Ambady Ramachandran, Nils Lehmann, Soile E. Puhakka, Giovanni Veronesi, Hongsheng Bi, Eiji Oda, Jia Li Duan, Per Tynelius, José María Huerta, Janne Schurmann Tolstrup, Rodrigo M. Carrillo-Larco, Rosangela Fernandes Lucena Batista, Victoria E Soto-Rojas, Hanno Ulmer, Shukri F. Mohamed, Anthony Kafatos, Suyeon Park, Mohsen Ibrahim, Hamed Pouraram, Bin Zhou, May Soe Aung, Lars Bo Andersen, Erfan Ghasemi, René Charles Sylva, Himanshu K. Chaturvedi, Luc Dauchet, Ahmad Ali Zainuddin, Angela Chetrit, Dan Zhu, Valérie Deschamps, Ko Ko Zaw, Peter Vollenweider, Tomas Vega, Yves Martin-Prével, Mahfuzar Rahman, Dorja Vočanec, Roman Topor-Madry, Vinay Nangia, Herculina S. Kruger, Asher Fawwad, Emily Sonestedt, Elena Pahomova, Aleksander Giwercman, Elżbieta Dziankowska-Zaborszczyk, Cecilia Björkelund, Tatjana Hejgaard, Maria Puiu, Maria Benedetta Donati, Andrew Wong, Carlos P. Boissonnet, Santosh K. Bhargava, Patrick Kolsteren, Dermot O'Reilly, Bahareh Kheiri, Wolfgang Kratzer, Susanne R. de Rooij, H. Bas Bueno-de-Mesquita, Günther Fink, José R. Banegas, Michele Monroy-Valle, Drude Molbo, Mahmudur Rahman, Hynek Pikhart, Rafael N. Pichardo, Massimo Salvetti, Hui Cai, Sarah Filippi, Georg Posch, Hung-Kwan So, Yonghua Hu, Katsuyasu Kouda, Joana Carvalho, Gailute Bernotiene, Hannu Uusitalo, Thein Thein Htay, Felix Kaducu, Maigeng Zhou, Lars Ängquist, Thi Tuyet-Hanh Tran, Charles Lunogelo, Michel Joffres, Sabina Zambon, Ronald D. 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Bojesen, Giuseppe Grosso, Seongjun Ha, Lauren Lissner, Mikhail Benet, Anastasia Markaki, Sanjay Rampal, Antônio Augusto Moura da Silva, Maria Lorenza Muiesan, Angelique Chan, Yvonne T. van der Schouw, Annamari Lundqvist, Philippe Amouyel, Kristyna Zejglicova, Charalambos Hadjigeorgiou, João Breda, Jørgen Meisfjord, Fatima Zahra Laamiri, Carl Lachat, Kai-Uwe Saum, Vilma Irazola, Leng Huat Foo, Óscar Lopes, Dickman Gareta, Flavio Nervi, Imre Janszky, Ruzena Kubinova, Terho Lehtimäki, Mario V. Capanzana, Moyses Szklo, Ramfis Nieto-Martínez, Viswanathan Mohan, Shuohua Chen, Arvind Pandey, Luigi Palmieri, Roya Kelishadi, Srinivasan Kannan, Jie Mi, Robert Beaglehole, Liliana Dacica, Jyrki K. Virtanen, Mohan Deepa, Peter Ueda, Isti Ilmiati Fujiati, Hermann Pohlabeln, Morten Sodemann, Jytte Halkjær, Zbigniew Kułaga, Sophie Visvikis-Siest, Farshad Farzadfar, Mohsen Azimi-Nezhad, Henry Völzke, Karolina Milkowska, Zahra Mohammadi, Belgin Ünal, Magda Gasull, George S. Stergiou, Marshall K. 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Mini, Viktoria Anna Kovacs, Rosemarie Martin, Nahla Hwalla, Wei Zheng, Hoang Van Minh, Edward D Janus, Laetitia Huiart, Farhad Pourfarzi, Sudha Ramachandra Rao, Fred Paccaud, Marcia Makdisse, Aye Aye Sein, Enrique Gutiérrez-González, Yang Yang, Anneke Blokstra, Henrike Galenkamp, Jaume Marrugat, Nazan Yardim, Wan Nazaimoon Wan Mohamud, Jesús Ibarluzea, Julio Zuñiga Cisneros, Laura Lauria, Argyro Karakosta, Dragana P Jovic, Jun Hata, Elio Riboli, Piotr Bandosz, Xun Tang, Parvina Mukhtorova, Jean Dallongeville, Jean-Bernard Ruidavets, Anne Tjønneland, Guillermo Frontera, Rahul Malhotra, Thomas Ferrao, Aleksandra Piwońska, Dusan Grafnetter, Mette Rasmussen, Daniel Weghuber, Sherali Rakhmatulloev, Martine Vrijheid, Johann Willeit, Motahareh Kheradmand, Małgorzata Mossakowska, Lechaba Tshepo, Dongfeng Gu, Hyeon Chang Kim, Vilmundur Gudnason, Maria Forsner, Peter Bjerregaard, Leon A. 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Horta, Macia Enguerran, Seyed Rasoul Zakavi, Daniel Fernández-Bergés, Kumiko Ohara, Ursula Kiechl-Kohlendorfer, Hermann Brenner, Przemyslaw Slusarczyk, Espen Bjertness, Jutta Stieber, Augusto Di Castelnuovo, Joel G. R. Roy, Aryeh D. Stein, Ruth Frikke-Schmidt, Vera Musil, Amaneh Shayanrad, Marcel Goldberg, Ramon O. Jimenez, Mohammad Reza Fattahi, Jolanda Hyska, Amir Houshang Mehrparvar, Elin Kolle, Mohamed Bamoshmoosh, Michelle Holdsworth, Felipe F. Casanueva, Børge G. Nordestgaard, Niels Wedderkopp, Eva Corpeleijn, Elias F. Gudmundsson, Antonio Mistretta, Daniel Lemogoum, Larissa Pruner Marques, Slavica Sović, Olli T. Raitakari, Marco Aurélio Peres, Alexandra Cucu, Gregorio Varela-Moreiras, Janine Clarke, Andrea Gazzinelli, Mieczysław Litwin, Sara Schramm, Xenophon Theodoridis, Harshpal Singh Sachdev, Mohammad Reza Mirjalili, Dimitrios Papandreou, Peter T. Katzmarzyk, Benjamin Acosta-Cazares, Ben Schöttker, Prabhdeep Kaur, Norlaila Mustafa, Shariq Rashid Masoodi, Sadaf G. Sepanlou, Adolfo Rubinstein, Francis Delpeuch, Julianne Williams, Abbas Dehghan, Leanne M. Riley, Heloisa Bettiol, Gabriele Nagel, Ellisiv B. Mathiesen, Ekaterina Stoyanova, Alisha N. Wade, Zhamyila Usupova, Arnaud Chiolero, Oonagh Markey, Jacqueline Ramke, Elena Bogova, Niveen M E Abu-Rmeileh, Nguyen D Nguyen, Tomasz Zdrojewski, Marjo-Riitta Järvelin, Jose Sanchez-Abanto, Rômulo Araújo Fernandes, Lourdes Ribas-Barba, Nalan Uysal, Mohamad Hasnan Ahmad, Krista Fischer, Maria Wany Louzada Strufaldi, Ramiro Guerrero, Farnam Mohebi, Tran Quoc Bao, Flávio Danni Fuchs, Salim Berkinbayev, Enisa Kujundzic, Sari Voutilainen, Farzad Hadaegh, Robert Lundqvist, Saeid Safiri, Iraj Mohebbi, George Luiz Lins Machado-Coelho, Annette Peters, Gonzalo Valdivia, Magdalena Korzycka, Rajiv T Erasmus, Masanori Iwasaki, Charmaine A. Duante, Sheikh Mohammed Shariful Islam, Quang Ngoc La, Ricky Eddie, Petra Rust, Daniela Rodrigues, Dirk De Bacquer, Karen Sparrenberger, Agneta Sjöberg, Thet Thet Mu, Katarzyna Dereń, Cora L. Craig, Jorge Motta, Janina Petkeviciene, Boyd Swinburn, Paibul Suriyawongpaisal, Visnja Djordjic, Ramón Alberto Rascón-Pacheco, Pradeep Joshi, Daan Kromhout, Marius B. Bjertness, Stefano Marventano, Juel Jarani, Alireza Khosravi, Eva Martos, David De Ridder, Lizzy M. Brewster, Nico Dragano, Liam Smeeth, Kenji Shibuya, Emma Ruiz Moreno, Hashem Jaddou, Grzegorz Sobek, Dimitrios Trichopoulos, Marvin Cervantes-Loaiza, Abu Am Hanif, Elaine M. Murtagh, Carlos A. Aguilar-Salinas, Graziella D'Arrigo, Kyungwon Oh, Heiner Boeing, Regina Heidinger-Felso, André Luiz Sena Guimarães, Balkish M. Naidu, Avula Laxmaiah, Ana M. B. Menezes, Marie Eliasen, Francesco Pistelli, Yuan He, Dusko Bjelica, José A. Casajús, Guang Ning, Lutgart Braeckman, Dirk Vanderschueren, Jochanan Stessman, Ivana Radic, Yi Zeng, Hans Concin, Damaskini Valvi, Sari Hantunen, Catherine Kyobutungi, Diego Augusto Santos Silva, Wenhua Zhao, Sok King Ong, Anne W. Taylor, Iraj Nabipour, Justyna Godos, Cyrus Cooper, Mattias Johansson, Samuel C. Dumith, Magdalena Muc, Sabine Schipf, Idowu O Senbanjo, Jim Mann, Rajaa Al-Raddadi, Yih Chung Tham, Kay-Tee Khaw, Joseph Cacciottolo, Ana Henriques, Sahar Saeedi Moghaddam, Reza Mohammadpourhodki, Bernhard O. Boehm, Songhomitra Panda-Jonas, Iveta Pudule, Elisabete Ramos, Lacramioara Aurelia Brinduse, Paul H. Lee, Terence W O'Neill, Javad Aghazadeh-Attari, Margus Punab, Bojan Jelaković, Camilla T. Damsgaard, Takafumi Ishida, Ekaterina Chikova-Iscener, Mirjam M. Heinen, Tazeen H. Jafar, Semánová Csilla, Constance Schultsz, Santiago F. Gomez, Raija Korpelainen, Edward W. Gregg, Laura Gutierrez, Pierre Traissac, Victor M. Herrera, Aristides M. Machado-Rodrigues, Fatemeh Malekzadeh, Shouling Wu, Jennifer L. Baker, Clicerio González-Villalpando, Eleonora d'Orsi, Irene G. M. van Valkengoed, Anna Fijałkowska, Wen-Harn Pan, Gregor Starc, Meghnath Dhimal, Murat Topbaş, George Moschonis, Robert Eggertsen, Abdullah Alkandari, Quang Ngoc Nguyen, Janette Walton, Elnaz Faramarzi, Saeed Dastgiri, Lien Braeckevelt, Nasheeta Peer, Radka Taxová Braunerová, Mohamed M. Ali, Steiner Krokstad, Harald Geiger, Morteza Shamshirgaran, Lela Shengelia, María Ángeles Dal Re Saavedra, Silvana Donoso, Khem Bahadur Karki, Timothy J. Key, Maria G. Grammatikopoulou, Susana Vale, Felix K. Assah, Juan A Rivera, Peter H. Whincup, Oana-Florentina Gheorghe-Fronea, Cassiano Ricardo Rech, Paul Ferdinand M. Reganit, Rachakulla Hari Kumar, Jaakko Mursu, Luis A. Moreno, Glen Gironella, Jelena Kos, Tilema Cama, Haakon E. Meyer, Jun Ma, Raphael E. Arku, Ziad Abdeen, Dianna J. Magliano, Jitendra Jonnagaddala, Konstantinos Gkiouras, Paola Nardone, Alberto Barceló, Tomi-Pekka Tuomainen, Francesco Gianfagna, Stefania Maggi, Mohammad Hossein Somi, Behrooz Hamzeh, Miquel Porta, Vesna Jureša, Alexander D. Deev, David Faeh, Antonio Bernabe-Ortiz, Sirkka Keinänen-Kiukaanniemi, Ian Hambleton, Stefan Savin, Andre Pascal Kengne, R. Krishna Kumar, Kurt Widhalm, Marco M Ferrario, Parisa Amiri, Anjani Kumar Jha, Thamara Hubler Figueiró, Jana Kratenova, Claudia M. Hormiga, Maria Tsigga, Zivka Dika, Indrapal I. Meshram, Ei Ei K. Nang, Ian Rouse, Rusidah Selamat, Paul Korrovits, Grethe S. Tell, Julie Taylor, Anabela Mota-Pinto, Paolo Vineis, Kotsedi D Monyeki, Khuong Quynh Long, Frank J Rühli, Shelly R. McFarlane, Sara Santos Sanz, Edyta Łuszczki, Maria G. Stathopoulou, Tara Coppinger, Karin De Ridder, Lucie Viet, Anna Bugge, Mehdi Yaseri, Safiah Md Yusof, Sandra C. Fuchs, Muhammad Islam, Irfan Nuhoglu, Rui Providência, Bernard Maire, Leandra Abarca-Gómez, Sinead Brophy, Maria Ruiz-Castell, Daniela Pierannunzio, Cristina Taddei, Gowri Mahasampath, Gustavo Velasquez-Melendez, Hanna Tolonen, Sudhir Kowlessur, Bagher Larijani, Laura Torres-Collado, Susi Kriemler, Ali Akbar Shayesteh, Cynthia Robitaille, Jorge Escobedo-de la Peña, Yufang Bi, Chinh Nguyen Huu, Line Tang Møllehave, Vincent Jr DeGennaro, Noor Ani Ahmad, Anar Dushpanova, Agustinus Soemantri, Susana Sans, Ionela Pascanu, Gwenaëlle Le Coroller, Inger Ariansen, Kodanda R Kanala, Gert B. M. Mensink, Abhijit Sen, Sergej M. Ostojic, Hanan F. Abdul Rahim, Hélène Delisle, Francisco J. Félix-Redondo, Yadlapalli S. Kusuma, Michael Knoflach, Moein Yoosefi, Tanja G. M. Vrijkotte, Wolfgang Ahrens, Osvaldo Santos, Bethlehem D. Solomon, Erik Lykke Mortensen, Nikhil D. Patel, Reynaldo Martorell, Ching-Yu Cheng, Stine Schramm, Hana Shimizu-Furusawa, Jacek Jóźwiak, Radwan Qasrawi, Herman Borghs, Zhanna Kalmatayeva, Heidi Klakk, Akram Pourshams, Naomi S. Levitt, Son Thai Pham, Simona Giampaoli, Dong Zhao, Indah Suci Widyahening, Merete Osler, Paula Margozzini, Silvia Bel-Serrat, Dora Romaguera, Monira Alarouj, Winsome R. Parnell, Marloes Cardol, Giota Touloumi, Janice Luisa Lukrafka, Adela Chirita-Emandi, Maryam Kavousi, Sanja Musić Milanović, Jean-Michel Gaspoz, Jalila El Ati, Sauli Herrala, Liang Xu, Pilar Guallar-Castillón, Bee Koon Poh, Luis Serra-Majem, Jonathan E. Shaw, Belong Cho, Daphne Mirkopoulou, Salvador Villalpando, Yuki Fujita, Tiffany K. Gill, Nish Chaturvedi, Erkin M. Mirrakhimov, Günay Can, Mark Woodward, Esther Lopez-Garcia, Mauro Virgílio Gomes de Barros, Ahmed A. Madar, Shoaib Afzal, Melanie J. Cowan, Gareth Stratton, Eduardo Salazar Martinez, Sameer Narake, Norie Sawada, Deepak Amarapurkar, Deepa Weerasekera, Diana A. Santos, Marjeta Majer, Herman Schargrodsky, Bruna Gonçalves Cordeiro da Silva, Ebrahim Eftekhar, Jesús Vioque, Marisa K. Sophiea, Teresa Shamah-Levy, María Dolores Chirlaque, Mohd Azahadi Omar, Stefan Söderberg, Isabel O. Oliveira, Joanne Katz, Xingwang Ye, Christophe Tzourio, Marie Zins, Aneta Weres, Ulrich Keil, Haiquan Xu, Akihiro Yoshihara, Rachel Dankner, Gabriella Gruden, Maroje Sorić, Hanspeter Stamm, Kim Overvad, Yanping Li, Carsten Oliver Schmidt, Christa L. Lilly, Veikko Salomaa, Gilad Twig, Senthil K Vasan, Qian Wang, Liufu Cui, Andrzej Galbarczyk, Sylvain Sebert, Wilma M. Hopman, Karl-Heinz Jöckel, Ari Voutilainen, Peter Schnohr, Jerzy Chudek, Katia Vergetti Bloch, Vincenzo Capuano, Jyh Eiin Wong, Torben Jørgensen, Anja Schienkiewitz, Nader Saki, Carolina Tarqui-Mamani, Maria Cecília Formoso Assunção, Kazi M. Jamil, Juraci Almeida Cesar, Pedro J Ortiz, Delphine De Smedt, Luciana Zaccagni, Lynne M. Boddy, Jie Hao, David Alejandro González-Chica, Romana Roccaldo, Sara Magnacca, Peter Stehle, Victoria Farrugia Sant'Angelo, Gry Skodje, Maryam Keramati, Tabara Yasuharu, Ali Ghanbari, Gyulli M. Kazakbaeva, Takuro Furusawa, Felicia Cañete, Kari Kuulasmaa, Justina Vaitkeviciute, (NCD-RisC), NCD Risk Factor Collaboration, Imperial College London, Harvard T.H. Chan School of Public Health, Middlesex University [London], Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Montpellier Interdisciplinary center on Sustainable Agri-food systems (Social and nutritional sciences) (UMR MoISA), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Centre International de Hautes Etudes Agronomiques Méditerranéennes - Institut Agronomique Méditerranéen de Montpellier (CIHEAM-IAMM), Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 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), Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Wellcome TrustEuropean Commission, Clinical Developmental Psychology, APH - Mental Health, Sociology, The Social Context of Aging (SoCA), Nutrition and Health, Iurilli, Maria LC [0000-0003-0409-1635], Zhou, Bin [0000-0002-1741-8628], Ezzati, Majid [0000-0002-2109-8081], Apollo - University of Cambridge Repository, Epidemiology and Data Science, APH - Aging & Later Life, APH - Societal Participation & Health, Public and occupational health, APH - Health Behaviors & Chronic Diseases, VU University medical center, APH - Personalized Medicine, AGEM - Endocrinology, metabolism and nutrition, ACS - Diabetes & metabolism, APH - Global Health, ARD - Amsterdam Reproduction and Development, Adult Psychiatry, Global Health, APH - Quality of Care, APH - Methodology, ACS - Atherosclerosis & ischemic syndromes, Gómez Santos, Santiago Felipe, NCD Risk Factor Collaboration (NCD-RisC), Faculdade de Desporto, Faculdade de Ciências da Nutrição e Alimentação, Faculdade de Medicina, Tampere University, Clinical Medicine, Department of Clinical Chemistry, Eye Centre, Harvard TH Chan School of Public Health, Middlesex University, World Health Organization, Ministry of Health, University of Lausanne, Eduardo Mondlane University, Victor Babes University of Medicine and Pharmacy Timisoara, University of Sydney, Health and Nutrition, University of Auckland, Seoul National University, ICMR - National Institute of Nutrition, Capital Medical University Beijing An Zhen Hospital, Universidad Peruana Cayetano Heredia, University Tunis El Manar, University of Oulu, University of Zagreb, University of Ljubljana, Caja Costarricense de Seguro Social, Al-Quds University, National Center of Public Healthcare, Qatar University, Birzeit University, Usmanu Danfodiyo University Teaching Hospital, Instituto Mexicano del Seguro Social, Flinders University, Mahidol University, BRAC James P Grant School of Public Health, University of Copenhagen, Copenhagen University Hospital, Food and Nutrition Research Institute, Urmia University of Medical Sciences, Instituto Nacional de Ciencias Médicas y Nutrición, University of Amsterdam, Shahrekord University of Medical Sciences, Non-Communicable Diseases Research Center, University of Oslo, University of Bremen, Republican Center for Health Promotion, Endocrinology and Genetics, Princess Nourah bint Abdulrahman University, Kuwait Institute for Scientific Research, King Abdulaziz University, Dasman Diabetes Institute, Aldara Hospital and Medical Center, King Abdullah International 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Basel, University of New South Wales, World Health Organization Country Office, Guilan University of Medical Sciences, University of Opole, Finnish Institute for Health and Welfare, Gulu University, University of Crete, Sri Venkateswara University, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Hellenic Medical Association for Obesity, National and Kapodistrian University of Athens, Maharajgunj Medical Campus, Aarhus University, Johns Hopkins Bloomberg School of Public Health, Pennington Biomedical Research Center, National Institute of Epidemiology, University of Münster, Israel Center for Disease Control, Research Institute for Primordial Prevention of Non- communicable Disease, Amsterdam UMC Public Health Research Institute, South African Medical Research Council, Kyrgyz State Medical Academy, Research Institute of Child Nutrition, Shahid Beheshti University of Medical Sciences, University of Cambridge, Mazandaran University of Medical Sciences, Hypertension Research Center, Medical University of Innsbruck, VASCage, Muhimbili University of Health and Allied Sciences, Yonsei University College of Medicine, National Cancer Center, Sahlgrenska University Hospital, University College South Denmark, Statistics Austria, B P Koirala Institute of Health Sciences, University of Vienna, Oulu Deaconess Institute Foundation, Tartu University Clinics, Kansai Medical University, Hungarian School Sport Federation, Ministry of Health and Quality of Life, University Hospital Ulm, North-West University, University of Jyväskylä, Amrita Institute of Medical Sciences, Institute of Endocrinology, All India Institute of Medical Sciences, African Population and Health Research Center, Hanoi University of Public Health, Hassan First University of Settat, Harokopio University, Sahlgrenska Academy, Endocrinology and Metabolism Research Center, University of Public Health, International Food Policy Research Institute, National University of Singapore, Hong Kong Polytechnic University, Tampere University Hospital, University of Douala, University of Cape Town, National Institute for Health Development, West Virginia University, Oswaldo Cruz Foundation Rene Rachou Research Institute, National Taiwan University, University of Chinese Academy of Sciences, Uppsala University, Taipei Medical University, Sports Medical Center of Minho, Universidad San Martín de Porres, Consejería de Sanidad Junta de Castilla y León, Universidade Federal de Ciências da Saúde de Porto Alegre, Norrbotten County Council, Ilembula Lutheran Hospital, Universidade Federal de Ouro Preto, University of Coimbra, Coimbra University Hospital Center, Institute of Neuroscience of the National Research Council, Baker Heart and Diabetes Institute, Agricultural University of Athens, Hospital Israelita Albert Einstein, SB RAS Federal Research Center Institute of Cytology and Genetics, University of Otago, University of Padua, Hellenic Mediterranean University, Loughborough 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Guatemala, University of Limpopo, University of Medical Sciences of Cienfuegos, Royal College of Surgeons in Ireland, La Trobe University, International Institute of Molecular and Cell Biology, Instituto Conmemorativo Gorgas de Estudios de la Salud, University of Brescia, Ministry of Health and Social Protection, University of Limerick, Croatian Institute of Public Health, Universiti Kebangsaan Malaysia, Bushehr University of Medical Sciences, Ulm University, Kobe University, Suraj Eye Institute, UNICEF, University Medicine Greifswald, National Institute of Hygiene and Epidemiology, University of Medicine and Pharmacy at Ho Chi Minh City, Hanoi Medical University, LifeDoc Health, Heartfile, Eastern Mediterranean Public Health Network, University of Manchester, State University of Medicine and Pharmacy, Tachikawa General Hospital, Korea Centers for Disease Control and Prevention, Japan Wildlife Research Center, Istanbul University, Universidade Federal do Paraná (UFPR), University of 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Pure Earth, Institute of Epidemiology Disease Control and Research, University of Turku, Institut Universitari d’Investigacióen AtencióPrima` ria Jordi Gol, Universiti Putra Malaysia, University of Malaya, Sotiria Hospital, University of Valencia, University of the Philippines, Slovak Academy of Sciences, Nutrition Research Foundation, Minas Gerais State Secretariat for Health, CS S. Agustín Ibsalut, Amsterdam Institute for Global Health and Development, National Institute of Health Doutor Ricardo Jorge, Universidade Nove de Julho, Public Health Agency of Canada, Canarian Health Service, Universidad Industrial de Santander, Associazione Calabrese di Epatologia, University of Minho, Fiji National University, Spanish Nutrition Foundation, Public Health Agency of Sweden, Institute of Food Sciences of the National Research Council, Sitaram Bhartia Institute of Science and Research, Kindergarten of Avlonari, National Institute of Health, Catalan Department of Health, Biodonostia Health Research Institute, Instituto de Saúde Ambiental, South Karelia Social and Health Care District, McMaster University, University of Saõ Paulo Clinics Hospital, Hospital Italiano de Buenos Aires, Rigshospitalet, Academic Medical Center of University of Amsterdam, The George Institute for Global Health, Center for Oral Health Services and Research Mid-Norway, Lagos State University College of Medicine, University of Las Palmas de Gran Canaria, Comenius University, National Center for Disease Control and Public Health, Nippon Medical School, Sungkyunkwan University, Finnish Institute of Occupational Health, Public Health Promotion and Development Organization, St Vincent’s Hospital, Nes Municipality, Health Polytechnic Jakarta II Institute, Diponegoro University, University of Bari, Institut Régional de SantéPublique, University of Bordeaux, Oslo Metropolitan University, Ss. Cyril and Methodius University, University of Leuven, Lamprecht und Stamm Sozialforschung und Beratung AG, Bonn University, National Institute of Public Health - National Institute of Hygiene, Kalina Malina Kindergarten, The Jikei University School of Medicine, Fu Jen Catholic University, National Statistical Office, Scientific Research Institute of Maternal and Child Health, University of Lincoln, Central University of Kerala, Amsterdam Public Health Research Institute, Health Service of Murcia, Institut d’Investigacio Sanitaria Illes Balears, University of Bologna, Hellenic Health Foundation, Government Medical College, Sefako Makgatho Health Science University, Addis Ababa University, Universidad Centro-Occidental Lisandro Alvarado, Meharry Medical College, Dokuz Eylul University, University of Tampere Tays Eye Center, Sabiha Gokcen Ilkokulu, Polytechnic Institute of Porto, Icahn School of Medicine at Mount Sinai, Universidad CEU San Pablo, University Miguel Hernandez, Vrije Universiteit Amsterdam, Sunflower Nursery School, North Karelia Center for Public Health, University of the Witwatersrand, Medical University of Vienna, Cork Institute of Technology, Institute for Medical Research, Xinjiang Medical University, Shanghai Educational Development Co. Ltd, Orebro University, University of London, Universitas Indonesia, Institute of Food and Nutrition Development of Ministry of Agriculture and Rural Affairs, Children’s Hospital of Fudan University, University of Cyprus, Niigata University, International Medical University, Iran University of Medical Sciences, Center for Diabetes and Endocrine Care, Peking University First Hospital, Jiangsu Provincial Center for Disease Control and Prevention, Sun Yat-sen University, West Kazakhstan Medical University, Inner Mongolia Medical University, University of Ghana, Maria Lc Iurilli , Bin Zhou , James E Bennett , Rodrigo M Carrillo-Larco , Marisa K Sophiea , Andrea Rodriguez-Martinez , Honor Bixby , Bethlehem D Solomon , Cristina Taddei , Goodarz Danaei , Mariachiara Di Cesare , Gretchen A Stevens , Leanne M Riley , Stefan Savin , Melanie J Cowan , Pascal Bovet , Albertino Damasceno , Adela Chirita-Emandi , Alison J Hayes , Nayu Ikeda , Rod T Jackson , Young-Ho Khang , Avula Laxmaiah , Jing Liu , J Jaime Miranda , Olfa Saidi , Sylvain Sebert , Maroje Sorić , Gregor Starc , Edward W Gregg , Leandra Abarca-Gómez , Ziad A Abdeen , Shynar Abdrakhmanova , Suhaila Abdul Ghaffar , Hanan F Abdul Rahim , Niveen M Abu-Rmeileh , Jamila Abubakar Garba , Benjamin Acosta-Cazares , Robert J Adams , Wichai Aekplakorn , Kaosar Afsana , Shoaib Afzal , Imelda A Agdeppa , Javad Aghazadeh-Attari , Carlos A Aguilar-Salinas , Charles Agyemang , Mohamad Hasnan Ahmad , Noor Ani Ahmad , Ali Ahmadi , Naser Ahmadi , Soheir H Ahmed , Wolfgang Ahrens , Gulmira Aitmurzaeva , Kamel Ajlouni , Hazzaa M Al-Hazzaa , Badreya Al-Lahou , Rajaa Al-Raddadi , Monira Alarouj , Fadia AlBuhairan , Shahla AlDhukair , Mohamed M Ali , Abdullah Alkandari , Ala'a Alkerwi , Kristine Allin , Mar Alvarez-Pedrerol , Eman Aly , Deepak N Amarapurkar , Parisa Amiri , Norbert Amougou , Philippe Amouyel , Lars Bo Andersen , Sigmund A Anderssen , Lars Ängquist , Ranjit Mohan Anjana , Alireza Ansari-Moghaddam , Hajer Aounallah-Skhiri , Joana Araújo , Inger Ariansen , Tahir Aris , Raphael E Arku , Nimmathota Arlappa , Krishna K Aryal , Thor Aspelund , Felix K Assah , Maria Cecília F Assunção , May Soe Aung , Juha Auvinen , Mária Avdicová , Shina Avi , Ana Azevedo , Mohsen Azimi-Nezhad , Fereidoun Azizi , Mehrdad Azmin , Bontha V Babu , Maja Bæksgaard Jørgensen , Azli Baharudin , Suhad Bahijri , Jennifer L Baker , Nagalla Balakrishna , Mohamed Bamoshmoosh , Maciej Banach , Piotr Bandosz , José R Banegas , Joanna Baran , Barbagallo CM, Alberto Barceló , Amina Barkat , Aluisio Jd Barros , Mauro Virgílio Gomes Barros , Abdul Basit , Joao Luiz D Bastos , Iqbal Bata , Anwar M Batieha , Rosangela L Batista , Zhamilya Battakova , Assembekov Batyrbek , Louise A Baur , Robert Beaglehole , Silvia Bel-Serrat , Antonisamy Belavendra , Habiba Ben Romdhane , Judith Benedics , Mikhail Benet , Ingunn Holden Bergh , Salim Berkinbayev , Antonio Bernabe-Ortiz , Gailute Bernotiene , Heloísa Bettiol , Jorge Bezerra , Aroor Bhagyalaxmi , Sumit Bharadwaj , Santosh K Bhargava , Zulfiqar A Bhutta , Hongsheng Bi , Yufang Bi , Daniel Bia , Elysée Claude Bika Lele, Mukharram M Bikbov , Bihungum Bista , Dusko J Bjelica , Peter Bjerregaard , Espen Bjertness , Marius B Bjertness , Cecilia Björkelund , Katia V Bloch , Anneke Blokstra , Simona Bo , Martin Bobak , Lynne M Boddy , Bernhard O Boehm , Heiner Boeing , Jose G Boggia , Elena Bogova , Carlos P Boissonnet , Stig E Bojesen , Marialaura Bonaccio , Vanina Bongard , Alice Bonilla-Vargas , Matthias Bopp , Herman Borghs , Lien Braeckevelt , Lutgart Braeckman , Marjolijn Ce Bragt , Imperia Brajkovich , Francesco Branca , Juergen Breckenkamp , João Breda , Hermann Brenner , Lizzy M Brewster , Garry R Brian , Lacramioara Brinduse , Sinead Brophy , Graziella Bruno , H Bas Bueno-de-Mesquita , Anna Bugge , Marta Buoncristiano , Genc Burazeri , Con Burns , Antonio Cabrera de León , Joseph Cacciottolo , Hui Cai , Tilema Cama , Christine Cameron , José Camolas , Günay Can , Ana Paula C Cândido , Felicia Cañete , Mario V Capanzana , Nadežda Capková , Eduardo Capuano , Vincenzo Capuano , Marloes Cardol , Viviane C Cardoso , Axel C Carlsson , Esteban Carmuega , Joana Carvalho , José A Casajús , Felipe F Casanueva , Ertugrul Celikcan , Laura Censi , Marvin Cervantes-Loaiza , Juraci A Cesar , Snehalatha Chamukuttan , Angelique W Chan , Queenie Chan , Himanshu K Chaturvedi , Nish Chaturvedi , Norsyamlina Che Abdul Rahim , Miao Li Chee , Chien-Jen Chen , Fangfang Chen , Huashuai Chen , Shuohua Chen , Zhengming Chen , Ching-Yu Cheng , Bahman Cheraghian , Angela Chetrit , Ekaterina Chikova-Iscener , Arnaud Chiolero , Shu-Ti Chiou , María-Dolores Chirlaque , Belong Cho , Kaare Christensen , Diego G Christofaro , Jerzy Chudek , Renata Cifkova , Michelle Cilia , Eliza Cinteza , Frank Claessens , Janine Clarke , Els Clays , Emmanuel Cohen , Hans Concin , Susana C Confortin , Cyrus Cooper , Tara C Coppinger , Eva Corpeleijn , Simona Costanzo , Dominique Cottel , Chris Cowell , Cora L Craig , Amelia C Crampin , Ana B Crujeiras , Semánová Csilla , Alexandra M Cucu , Liufu Cui , Felipe V Cureau , Ewelina Czenczek-Lewandowska , Graziella D'Arrigo , Eleonora d'Orsi , Liliana Dacica , María Ángeles Dal Re Saavedra , Jean Dallongeville , Camilla T Damsgaard , Rachel Dankner , Thomas M Dantoft , Parasmani Dasgupta , Saeed Dastgiri , Luc Dauchet , Kairat Davletov , Guy De Backer , Dirk De Bacquer , Giovanni de Gaetano , Stefaan De Henauw , Paula Duarte de Oliveira , David De Ridder , Karin De Ridder , Susanne R de Rooij , Delphine De Smedt , Mohan Deepa , Alexander D Deev , Vincent Jr DeGennaro , Abbas Dehghan , Hélène Delisle , Francis Delpeuch , Stefaan Demarest , Elaine Dennison , Katarzyna Dereń , Valérie Deschamps , Meghnath Dhimal , Augusto F Di Castelnuovo , Juvenal Soares Dias-da-Costa , María Elena Díaz-Sánchez , Alejandro Diaz , Zivka Dika , Shirin Djalalinia , Visnja Djordjic , Ha Tp Do , Annette J Dobson , Maria Benedetta Donati , Chiara Donfrancesco , Silvana P Donoso , Angela Döring , Maria Dorobantu , Ahmad Reza Dorosty , Kouamelan Doua , Nico Dragano , Wojciech Drygas , Jia Li Duan , Charmaine A Duante , Priscilla Duboz , Rosemary B Duda , Vesselka Duleva , Virginija Dulskiene , Samuel C Dumith , Anar Dushpanova , Vilnis Dzerve , Elzbieta Dziankowska-Zaborszczyk , Ricky Eddie , Ebrahim Eftekhar , Eruke E Egbagbe , Robert Eggertsen , Sareh Eghtesad , Gabriele Eiben , Ulf Ekelund , Mohammad El-Khateeb , Jalila El Ati , Denise Eldemire-Shearer , Marie Eliasen , Paul Elliott , Reina Engle-Stone , Macia Enguerran , Rajiv T Erasmus , Raimund Erbel , Cihangir Erem , Louise Eriksen , Johan G Eriksson , Jorge Escobedo-de la Peña , Saeid Eslami , Ali Esmaeili , Alun Evans , David Faeh , Albina A Fakhretdinova , Caroline H Fall , Elnaz Faramarzi , Mojtaba Farjam , Victoria Farrugia Sant'Angelo , Farshad Farzadfar , Mohammad Reza Fattahi , Asher Fawwad , Francisco J Felix-Redondo , Trevor S Ferguson , Romulo A Fernandes , Daniel Fernández-Bergés , Daniel Ferrante , Thomas Ferrao , Marika Ferrari , Marco M Ferrario , Catterina Ferreccio , Eldridge Ferrer , Jean Ferrieres , Thamara Hubler Figueiró , Anna Fijalkowska , Günther Fink , Krista Fischer , Leng Huat Foo , Maria Forsner , Heba M Fouad , Damian K Francis , Maria do Carmo Franco , Ruth Frikke-Schmidt , Guillermo Frontera , Flavio D Fuchs , Sandra C Fuchs , Isti I Fujiati , Yuki Fujita , Matsuda Fumihiko , Takuro Furusawa , Zbigniew Gaciong , Mihai Gafencu , Andrzej Galbarczyk , Henrike Galenkamp , Daniela Galeone , Myriam Galfo , Fabio Galvano , Jingli Gao , Manoli Garcia-de-la-Hera , Marta García-Solano , Dickman Gareta , Sarah P Garnett , Jean-Michel Gaspoz , Magda Gasull , Adroaldo Cesar Araujo Gaya , Anelise Reis Gaya , Andrea Gazzinelli , Ulrike Gehring , Harald Geiger , Johanna M Geleijnse , Ali Ghanbari , Erfan Ghasemi , Oana-Florentina Gheorghe-Fronea , Simona Giampaoli , Francesco Gianfagna , Tiffany K Gill , Jonathan Giovannelli , Glen Gironella , Aleksander Giwercman , Konstantinos Gkiouras , Justyna Godos , Sibel Gogen , Marcel Goldberg , Rebecca A Goldsmith , David Goltzman , Santiago F Gómez , Aleksandra Gomula , Bruna Goncalves Cordeiro da Silva , Helen Gonçalves , David A Gonzalez-Chica , Marcela Gonzalez-Gross , Margot González-Leon , Juan P González-Rivas , Clicerio González-Villalpando , María-Elena González-Villalpando , Angel R Gonzalez , Frederic Gottrand , Antonio Pedro Graça , Sidsel Graff-Iversen , Dušan Grafnetter , Aneta Grajda , Maria G Grammatikopoulou , Ronald D Gregor , Tomasz Grodzicki , Else Karin Grøholt , Anders Grøntved , Giuseppe Grosso , Gabriella Gruden , Dongfeng Gu , Emanuela Gualdi-Russo , Pilar Guallar-Castillón , Andrea Gualtieri , Elias F Gudmundsson , Vilmundur Gudnason , Ramiro Guerrero , Idris Guessous , Andre L Guimaraes , Martin C Gulliford , Johanna Gunnlaugsdottir , Marc J Gunter , Xiu-Hua Guo , Yin Guo , Prakash C Gupta , Rajeev Gupta , Oye Gureje , Beata Gurzkowska , Enrique Gutiérrez-González , Laura Gutierrez , Felix Gutzwiller , Seongjun Ha , Farzad Hadaegh , Charalambos A Hadjigeorgiou , Rosa Haghshenas , Hamid Hakimi , Jytte Halkjær , Ian R Hambleton , Behrooz Hamzeh , Dominique Hange , Abu Am Hanif , Sari Hantunen , Jie Hao , Rachakulla Hari Kumar , Seyed Mohammad Hashemi-Shahri , Maria Hassapidou , Jun Hata , Teresa Haugsgjerd , Jiang He , Yuan He , Yuna He , Regina Heidinger-Felso , Mirjam Heinen , Tatjana Hejgaard , Marleen Elisabeth Hendriks , Rafael Dos Santos Henrique , Ana Henriques , Leticia Hernandez Cadena , Sauli Herrala , Victor M Herrera , Isabelle Herter-Aeberli , Ramin Heshmat , Allan G Hill , Sai Yin Ho , Suzanne C Ho , Michael Hobbs , Michelle Holdsworth , Reza Homayounfar , Clara Homs , Wilma M Hopman , Andrea Rvr Horimoto , Claudia M Hormiga , Bernardo L Horta , Leila Houti , Christina Howitt , Thein Thein Htay , Aung Soe Htet , Maung Maung Than Htike , Yonghua Hu , José María Huerta , Ilpo Tapani Huhtaniemi , Laetitia Huiart , Constanta Huidumac Petrescu , Martijn Huisman , Abdullatif Husseini , Chinh Nguyen Huu , Inge Huybrechts , Nahla Hwalla , Jolanda Hyska , Licia Iacoviello , Jesús M Ibarluzea , Mohsen M Ibrahim , Norazizah Ibrahim Wong , M Arfan Ikram , Violeta Iotova , Vilma E Irazola , Takafumi Ishida , Muhammad Islam , Sheikh Mohammed Shariful Islam , Masanori Iwasaki , Jeremy M Jacobs , Hashem Y Jaddou , Tazeen Jafar , Kenneth James , Kazi M Jamil , Konrad Jamrozik , Imre Janszky , Edward Janus , Juel Jarani , Marjo-Riitta Jarvelin , Grazyna Jasienska , Ana Jelakovic , Bojan Jelakovic , Garry Jennings , Anjani Kumar Jha , Chao Qiang Jiang , Ramon O Jimenez , Karl-Heinz Jöckel , Michel Joffres , Mattias Johansson , Jari J Jokelainen , Jost B Jonas , Jitendra Jonnagaddala , Torben Jørgensen , Pradeep Joshi , Farahnaz Joukar , Dragana P Jovic , Jacek J Jóźwiak , Anne Juolevi , Gregor Jurak , Iulia Jurca Simina , Vesna Juresa , Rudolf Kaaks , Felix O Kaducu , Anthony Kafatos , Eero O Kajantie , Zhanna Kalmatayeva , Ofra Kalter-Leibovici , Yves Kameli , Freja B Kampmann , Kodanda R Kanala , Srinivasan Kannan , Efthymios Kapantais , Argyro Karakosta , Line L Kårhus , Khem B Karki , Marzieh Katibeh , Joanne Katz , Peter T Katzmarzyk , Jussi Kauhanen , Prabhdeep Kaur , Maryam Kavousi , Gyulli M Kazakbaeva , Ulrich Keil , Lital Keinan Boker , Sirkka Keinänen-Kiukaanniemi , Roya Kelishadi , Cecily Kelleher , Han Cg Kemper , Andre P Kengne , Maryam Keramati , Alina Kerimkulova , Mathilde Kersting , Timothy Key , Yousef Saleh Khader , Davood Khalili , Kay-Tee Khaw , Bahareh Kheiri , Motahareh Kheradmand , Alireza Khosravi , Ilse Msl Khouw , Ursula Kiechl-Kohlendorfer , Stefan Kiechl , Japhet Killewo , Dong Wook Kim , Hyeon Chang Kim , Jeongseon Kim , Jenny M Kindblom , Heidi Klakk , Magdalena Klimek , Jeannette Klimont , Jurate Klumbiene , Michael Knoflach , Bhawesh Koirala , Elin Kolle , Patrick Kolsteren , Jürgen König , Raija Korpelainen , Paul Korrovits , Magdalena Korzycka , Jelena Kos , Seppo Koskinen , Katsuyasu Kouda , Viktoria A Kovacs , Sudhir Kowlessur , Slawomir Koziel , Jana Kratenova , Wolfgang Kratzer , Susi Kriemler , Peter Lund Kristensen , Steinar Krokstad , Daan Kromhout , Herculina S Kruger , Ruzena Kubinova , Renata Kuciene , Urho M Kujala , Enisa Kujundzic , Zbigniew Kulaga , R Krishna Kumar , Marie Kunešová , Pawel Kurjata , Yadlapalli S Kusuma , Kari Kuulasmaa , Catherine Kyobutungi , Quang Ngoc La , Fatima Zahra Laamiri , Tiina Laatikainen , Carl Lachat , Youcef Laid , Tai Hing Lam , Christina-Paulina Lambrinou , Edwige Landais , Vera Lanska , Georg Lappas , Bagher Larijani , Tint Swe Latt , Laura Lauria , Maria Lazo-Porras , Gwenaëlle Le Coroller , Khanh Le Nguyen Bao , Agnès Le Port , Tuyen D Le , Jeannette Lee , Jeonghee Lee , Paul H Lee , Nils Lehmann , Terho Lehtimäki , Daniel Lemogoum , Naomi S Levitt , Yanping Li , Merike Liivak , Christa L Lilly , Wei-Yen Lim , M Fernanda Lima-Costa , Hsien-Ho Lin , Xu Lin , Yi-Ting Lin , Lars Lind , Allan Linneberg , Lauren Lissner , Mieczyslaw Litwin , Lijuan Liu , Wei-Cheng Lo , Helle-Mai Loit , Khuong Quynh Long , Luis Lopes , Oscar Lopes , Esther Lopez-Garcia , Tania Lopez , Paulo A Lotufo , José Eugenio Lozano , Janice L Lukrafka , Dalia Luksiene , Annamari Lundqvist , Robert Lundqvist , Nuno Lunet , Charles Lunogelo , Michala Lustigová , Edyta Łuszczki , Guansheng Ma , Jun Ma , Xu Ma , George Ll Machado-Coelho , Aristides M Machado-Rodrigues , Luisa M Macieira , Ahmed A Madar , Stefania Maggi , Dianna J Magliano , Sara Magnacca , Emmanuella Magriplis , Gowri Mahasampath , Bernard Maire , Marjeta Majer , Marcia Makdisse , Päivi Mäki , Fatemeh Malekzadeh , Reza Malekzadeh , Rahul Malhotra , Kodavanti Mallikharjuna Rao , Sofia K Malyutina , Lynell V Maniego , Yannis Manios , Jim I Mann , Fariborz Mansour-Ghanaei , Enzo Manzato , Paula Margozzini , Anastasia Markaki , Oonagh Markey , Eliza Markidou Ioannidou , Pedro Marques-Vidal , Larissa Pruner Marques , Jaume Marrugat , Yves Martin-Prevel , Rosemarie Martin , Reynaldo Martorell , Eva Martos , Katharina Maruszczak , Stefano Marventano , Luis P Mascarenhas , Shariq R Masoodi , Ellisiv B Mathiesen , Prashant Mathur , Alicia Matijasevich , Tandi E Matsha , Christina Mavrogianni , Artur Mazur , Jean Claude N Mbanya , Shelly R McFarlane , Stephen T McGarvey , Martin McKee , Stela McLachlan , Rachael M McLean , Scott B McLean , Breige A McNulty , Sounnia Mediene Benchekor , Jurate Medzioniene , Parinaz Mehdipour , Kirsten Mehlig , Amir Houshang Mehrparvar , Aline Meirhaeghe , Jørgen Meisfjord , Christa Meisinger , Ana Maria B Menezes , Geetha R Menon , Gert Bm Mensink , Maria Teresa Menzano , Alibek Mereke , Indrapal I Meshram , Andres Metspalu , Haakon E Meyer , Jie Mi , Kim F Michaelsen , Nathalie Michels , Kairit Mikkel , Karolina Milkowska , Jody C Miller , Cláudia S Minderico , G K Mini , Juan Francisco Miquel , Mohammad Reza Mirjalili , Daphne Mirkopoulou , Erkin Mirrakhimov , Marjeta Mišigoj-Durakovic , Antonio Mistretta , Veronica Mocanu , Pietro A Modesti , Sahar Saeedi Moghaddam , Bahram Mohajer , Mostafa K Mohamed , Shukri F Mohamed , Kazem Mohammad , Zahra Mohammadi , Noushin Mohammadifard , Reza Mohammadpourhodki , Viswanathan Mohan , Salim Mohanna , Muhammad Fadhli Mohd Yusoff , Iraj Mohebbi , Farnam Mohebi , Marie Moitry , Drude Molbo , Line T Møllehave , Niels C Møller , Dénes Molnár , Amirabbas Momenan , Charles K Mondo , Michele Monroy-Valle , Eric Monterrubio-Flores , Kotsedi Daniel K Monyeki , Jin Soo Moon , Mahmood Moosazadeh , Leila B Moreira , Alain Morejon , Luis A Moreno , Karen Morgan , Suzanne N Morin , Erik Lykke Mortensen , George Moschonis , Malgorzata Mossakowska , Aya Mostafa , Anabela Mota-Pinto , Jorge Mota , Mohammad Esmaeel Motlagh , Jorge Motta , Marcos André Moura-Dos-Santos , Malay K Mridha , Kelias P Msyamboza , Thet Thet Mu , Magdalena Muc , Boban Mugoša , Maria L Muiesan , Parvina Mukhtorova , Martina Müller-Nurasyid , Neil Murphy , Jaakko Mursu , Elaine M Murtagh , Kamarul Imran Musa , Sanja Music Milanovic , Vera Musil , Norlaila Mustafa , Iraj Nabipour , Shohreh Naderimagham , Gabriele Nagel , Balkish M Naidu , Farid Najafi , Harunobu Nakamura , Jana Námešná , Ei Ei K Nang , Vinay B Nangia , Martin Nankap , Sameer Narake , Paola Nardone , Matthias Nauck , William A Neal , Azim Nejatizadeh , Chandini Nekkantti , Keiu Nelis , Liis Nelis , Ilona Nenko , Martin Neovius , Flavio Nervi , Chung T Nguyen , Nguyen D Nguyen , Quang Ngoc Nguyen , Ramfis E Nieto-Martínez , Yury P Nikitin , Guang Ning , Toshiharu Ninomiya , Sania Nishtar , Marianna Noale , Oscar A Noboa , Helena Nogueira , Teresa Norat , Maria Nordendahl , Børge G Nordestgaard , Davide Noto , Natalia Nowak-Szczepanska , Mohannad Al Nsour , Irfan Nuhoglu , Eha Nurk , Terence W O'Neill , Dermot O'Reilly , Galina Obreja , Caleb Ochimana , Angélica M Ochoa-Avilés , Eiji Oda , Kyungwon Oh , Kumiko Ohara , Claes Ohlsson , Ryutaro Ohtsuka , Örn Olafsson , Maria Teresa A Olinto , Isabel O Oliveira , Mohd Azahadi Omar , Altan Onat , Sok King Ong , Lariane M Ono , Pedro Ordunez , Rui Ornelas , Ana P Ortiz , Pedro J Ortiz , Merete Osler , Clive Osmond , Sergej M Ostojic , Afshin Ostovar , Johanna A Otero , Kim Overvad , Ellis Owusu-Dabo , Fred Michel Paccaud , Cristina Padez , Ioannis Pagkalos , Elena Pahomova , Karina Mary de Paiva , Andrzej Pajak , Domenico Palli , Alberto Palloni , Luigi Palmieri , Wen-Harn Pan , Songhomitra Panda-Jonas , Arvind Pandey , Francesco Panza , Dimitrios Papandreou , Soon-Woo Park , Suyeon Park , Winsome R Parnell , Mahboubeh Parsaeian , Ionela M Pascanu , Patrick Pasquet , Nikhil D Patel , Ivan Pecin , Mangesh S Pednekar , Nasheeta Peer , Gao Pei , Sergio Viana Peixoto , Markku Peltonen , Alexandre C Pereira , Marco A Peres , Napoleón Pérez-Farinós , Cynthia M Pérez , Valentina Peterkova , Annette Peters , Astrid Petersmann , Janina Petkeviciene , Ausra Petrauskiene , Emanuela Pettenuzzo , Niloofar Peykari , Son Thai Pham , Rafael N Pichardo , Daniela Pierannunzio , Iris Pigeot , Hynek Pikhart , Aida Pilav , Lorenza Pilotto , Francesco Pistelli , Freda Pitakaka , Aleksandra Piwonska , Andreia N Pizarro , Pedro Plans-Rubió , Bee Koon Poh , Hermann Pohlabeln , Raluca M Pop , Stevo R Popovic , Miquel Porta , Georg Posch , Anil Poudyal , Dimitrios Poulimeneas , Hamed Pouraram , Farhad Pourfarzi , Akram Pourshams , Hossein Poustchi , Rajendra Pradeepa , Alison J Price , Jacqueline F Price , Rui Providencia , Jardena J Puder , Iveta Pudule , Soile E Puhakka , Maria Puiu , Margus Punab , Radwan F Qasrawi , Mostafa Qorbani , Tran Quoc Bao , Ivana Radic , Ricardas Radisauskas , Salar Rahimikazerooni , Mahfuzar Rahman , Mahmudur Rahman , Olli Raitakari , Manu Raj , Ellina Rakhimova , Sherali Rakhmatulloev , Ivo Rakovac , Sudha Ramachandra Rao , Ambady Ramachandran , Jacqueline Ramke , Elisabete Ramos , Rafel Ramos , Lekhraj Rampal , Sanjay Rampal , Vayia Rarra , Ramon A Rascon-Pacheco , Mette Rasmussen , Cassiano Ricardo Rech , Josep Redon , Paul Ferdinand M Reganit , Valéria Regecová , Luis Revilla , Abbas Rezaianzadeh , Lourdes Ribas-Barba , Robespierre Ribeiro , Elio Riboli , Adrian Richter , Fernando Rigo , Natascia Rinaldo , Tobias F Rinke de Wit , Ana Rito , Raphael M Ritti-Dias , Juan A Rivera , Cynthia Robitaille , Romana Roccaldo , Daniela Rodrigues , Fernando Rodríguez-Artalejo , María Del Cristo Rodriguez-Perez , Laura A Rodríguez-Villamizar , Ulla Roggenbuck , Rosalba Rojas-Martinez , Nipa Rojroongwasinkul , Dora Romaguera , Elisabetta L Romeo , Rafaela V Rosario , Annika Rosengren , Ian Rouse , Joel Gr Roy , Adolfo Rubinstein , Frank J Rühli , Jean-Bernard Ruidavets , Blanca Sandra Ruiz-Betancourt , Maria Ruiz-Castell , Emma Ruiz Moreno , Iuliia A Rusakova , Kenisha Russell Jonsson , Paola Russo , Petra Rust , Marcin Rutkowski , Charumathi Sabanayagam , Elena Sacchini , Harshpal S Sachdev , Alireza Sadjadi , Ali Reza Safarpour , Saeid Safiri , Nader Saki , Benoit Salanave , Eduardo Salazar Martinez , Diego Salmerón , Veikko Salomaa , Jukka T Salonen , Massimo Salvetti , Margarita Samoutian , Jose Sánchez-Abanto , Sandjaja , Susana Sans , Loreto Santa Marina , Diana A Santos , Ina S Santos , Lèlita C Santos , Maria Paula Santos , Osvaldo Santos , Rute Santos , Sara Santos Sanz , Jouko L Saramies , Luis B Sardinha , Nizal Sarrafzadegan , Thirunavukkarasu Sathish , Kai-Uwe Saum , Savvas Savva , Mathilde Savy , Norie Sawada , Mariana Sbaraini , Marcia Scazufca , Beatriz D Schaan , Angelika Schaffrath Rosario , Herman Schargrodsky , Anja Schienkiewitz , Sabine Schipf , Carsten O Schmidt , Ida Maria Schmidt , Peter Schnohr , Ben Schöttker , Sara Schramm , Stine Schramm , Helmut Schröder , Constance Schultsz , Aletta E Schutte , Aye Aye Sein , Rusidah Selamat , Vedrana Sember , Abhijit Sen , Idowu O Senbanjo , Sadaf G Sepanlou , Victor Sequera , Luis Serra-Majem , Jennifer Servais , Ludmila Ševcíková , Svetlana A Shalnova , Teresa Shamah-Levy , Morteza Shamshirgaran , Coimbatore Subramaniam Shanthirani , Maryam Sharafkhah , Sanjib K Sharma , Jonathan E Shaw , Amaneh Shayanrad , Ali Akbar Shayesteh , Lela Shengelia , Zumin Shi , Kenji Shibuya , Hana Shimizu-Furusawa , Dong Wook Shin , Majid Shirani , Rahman Shiri , Namuna Shrestha , Khairil Si-Ramlee , Alfonso Siani , Rosalynn Siantar , Abla M Sibai , Antonio M Silva , Diego Augusto Santos Silva , Mary Simon , Judith Simons , Leon A Simons , Agneta Sjöberg , Michael Sjöström , Gry Skodje , Jolanta Slowikowska-Hilczer , Przemyslaw Slusarczyk , Liam Smeeth , Hung-Kwan So , Fernanda Cunha Soares , Grzegorz Sobek , Eugène Sobngwi , Morten Sodemann , Stefan Söderberg , Moesijanti Ye Soekatri , Agustinus Soemantri , Reecha Sofat , Vincenzo Solfrizzi , Mohammad Hossein Somi , Emily Sonestedt , Yi Song , Thorkild Ia Sørensen , Elin P Sørgjerd , Charles Sossa Jérome , Victoria E Soto-Rojas , Aïcha Soumaré , Slavica Sovic , Bente Sparboe-Nilsen , Karen Sparrenberger , Angela Spinelli , Igor Spiroski , Jan A Staessen , Hanspeter Stamm , Maria G Stathopoulou , Kaspar Staub , Bill Stavreski , Jostein Steene-Johannessen , Peter Stehle , Aryeh D Stein , George S Stergiou , Jochanan Stessman , Ranko Stevanovic , Jutta Stieber , Doris Stöckl , Tanja Stocks , Jakub Stokwiszewski , Ekaterina Stoyanova , Gareth Stratton , Karien Stronks , Maria Wany Strufaldi , Lela Sturua , Ramón Suárez-Medina , Machi Suka , Chien-An Sun , Johan Sundström , Yn-Tz Sung , Jordi Sunyer , Paibul Suriyawongpaisal , Boyd A Swinburn , Rody G Sy , Holly E Syddall , René Charles Sylva , Moyses Szklo , Lucjan Szponar , E Shyong Tai , Mari-Liis Tammesoo , Abdonas Tamosiunas , Eng Joo Tan , Xun Tang , Maya Tanrygulyyeva , Frank Tanser , Yong Tao , Mohammed Rasoul Tarawneh , Jakob Tarp , Carolina B Tarqui-Mamani , Radka Taxová Braunerová , Anne Taylor , Julie Taylor , Félicité Tchibindat , William R Tebar , Grethe S Tell , Tania Tello , Yih Chung Tham , K R Thankappan , Holger Theobald , Xenophon Theodoridis , Lutgarde Thijs , Nihal Thomas , Betina H Thuesen , Lubica Tichá , Erik J Timmermans , Anne Tjonneland , Hanna K Tolonen , Janne S Tolstrup , Murat Topbas , Roman Topór-Madry , Liv Elin Torheim , María José Tormo , Michael J Tornaritis , Maties Torrent , Laura Torres-Collado , Stefania Toselli , Giota Touloumi , Pierre Traissac , Thi Tuyet-Hanh Tran , Dimitrios Trichopoulos , Antonia Trichopoulou , Oanh Th Trinh , Atul Trivedi , Lechaba Tshepo , Maria Tsigga , Shoichiro Tsugane , Azaliia M Tuliakova , Marshall K Tulloch-Reid , Fikru Tullu , Tomi-Pekka Tuomainen , Jaakko Tuomilehto , Maria L Turley , Gilad Twig , Per Tynelius , Themistoklis Tzotzas , Christophe Tzourio , Peter Ueda , Eunice Ugel , Flora Am Ukoli , Hanno Ulmer , Belgin Unal , Zhamyila Usupova , Hannu Mt Uusitalo , Nalan Uysal , Justina Vaitkeviciute , Gonzalo Valdivia , Susana Vale , Damaskini Valvi , Rob M van Dam , Johan Van der Heyden , Yvonne T van der Schouw , Koen Van Herck , Hoang Van Minh , Natasja M 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Paola, Nauck, Matthia, Neal, William A, Nejatizadeh, Azim, Nekkantti, Chandini, Nelis, Keiu, Nelis, Lii, Nenko, Ilona, Neovius, Martin, Nervi, Flavio, Nguyen, Chung T, Nguyen, Nguyen D, Nguyen, Quang Ngoc, Nieto-Martínez, Ramfis E, Nikitin, Yury P, Ning, Guang, Ninomiya, Toshiharu, Nishtar, Sania, Noale, Marianna, Noboa, Oscar A, Nogueira, Helena, Norat, Teresa, Nordendahl, Maria, Nordestgaard, Børge G, Noto, Davide, Nowak-Szczepanska, Natalia, Al Nsour, Mohannad, Nuhoglu, Irfan, Nurk, Eha, O'Neill, Terence W, O'Reilly, Dermot, Obreja, Galina, Ochimana, Caleb, Ochoa-Avilés, Angélica M, Oda, Eiji, Oh, Kyungwon, Ohara, Kumiko, Ohlsson, Clae, Ohtsuka, Ryutaro, Olafsson, Örn, Olinto, Maria Teresa A, Oliveira, Isabel O, Omar, Mohd Azahadi, Onat, Altan, Ong, Sok King, Ono, Lariane M, Ordunez, Pedro, Ornelas, Rui, Ortiz, Ana P, Ortiz, Pedro J, Osler, Merete, Osmond, Clive, Ostojic, Sergej M, Ostovar, Afshin, Otero, Johanna A, Overvad, Kim, Owusu-Dabo, Elli, Paccaud, Fred Michel, Padez, 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Cynthia, Roccaldo, Romana, Rodrigues, Daniela, Rodríguez-Artalejo, Fernando, del Cristo Rodriguez-Perez, María, Rodríguez-Villamizar, Laura A, Roggenbuck, Ulla, Rojas-Martinez, Rosalba, Rojroongwasinkul, Nipa, Romaguera, Dora, Romeo, Elisabetta L, Rosario, Rafaela V, Rosengren, Annika, Rouse, Ian, Roy, Joel GR, Rubinstein, Adolfo, Rühli, Frank J, Ruidavets, Jean-Bernard, Ruiz-Betancourt, Blanca Sandra, Ruiz-Castell, Maria, Moreno, Emma Ruiz, Rusakova, Iuliia A, Jonsson, Kenisha Russell, Russo, Paola, Rust, Petra, Rutkowski, Marcin, Sabanayagam, Charumathi, Sacchini, Elena, Sachdev, Harshpal S, Sadjadi, Alireza, Safarpour, Ali Reza, Safiri, Saeid, Saki, Nader, Salanave, Benoit, Martinez, Eduardo Salazar, Salmerón, Diego, Salomaa, Veikko, Salonen, Jukka T, Salvetti, Massimo, Samoutian, Margarita, Sánchez-Abanto, Jose, Sandjaja, null, Sans, Susana, Marina, Loreto Santa, Santos, Diana A, Santos, Ina S, Santos, Lèlita C, Santos, Maria Paula, Santos, Osvaldo, Santos, Rute, Sanz, Sara Santo, Saramies, Jouko L, Sardinha, Luis B, Sarrafzadegan, Nizal, Sathish, Thirunavukkarasu, Saum, Kai-Uwe, Savva, Savva, Savy, Mathilde, Sawada, Norie, Sbaraini, Mariana, Scazufca, Marcia, Schaan, Beatriz D, Rosario, Angelika Schaffrath, Schargrodsky, Herman, Schienkiewitz, Anja, Schipf, Sabine, Schmidt, Carsten O, Schmidt, Ida Maria, Schnohr, Peter, Schöttker, Ben, Schramm, Sara, Schramm, Stine, Schröder, Helmut, Schultsz, Constance, Schutte, Aletta E, Sein, Aye Aye, Selamat, Rusidah, Sember, Vedrana, Sen, Abhijit, Senbanjo, Idowu O, Sepanlou, Sadaf G, Sequera, Victor, Serra-Majem, Lui, Servais, Jennifer, Ševcíková, Ludmila, Shalnova, Svetlana A, Shamah-Levy, Teresa, Shamshirgaran, Morteza, Shanthirani, Coimbatore Subramaniam, Sharafkhah, Maryam, Sharma, Sanjib K, Shaw, Jonathan E, Shayanrad, Amaneh, Shayesteh, Ali Akbar, Shengelia, Lela, Shi, Zumin, Shibuya, Kenji, Shimizu-Furusawa, Hana, Shin, Dong Wook, Shirani, Majid, Shiri, Rahman, Shrestha, Namuna, Si-Ramlee, Khairil, Siani, Alfonso, Siantar, Rosalynn, Sibai, Abla M, Silva, Antonio M, Silva, Diego Augusto Santo, Simon, Mary, Simons, Judith, Simons, Leon A, Sjöberg, Agneta, Sjöström, Michael, Skodje, Gry, Slowikowska-Hilczer, Jolanta, Slusarczyk, Przemyslaw, Smeeth, Liam, So, Hung-Kwan, Soares, Fernanda Cunha, Sobek, Grzegorz, Sobngwi, Eugène, Sodemann, Morten, Söderberg, Stefan, Soekatri, Moesijanti YE, Soemantri, Agustinu, Sofat, Reecha, Solfrizzi, Vincenzo, Somi, Mohammad Hossein, Sonestedt, Emily, Song, Yi, Sørensen, Thorkild IA, Sørgjerd, Elin P, Jérome, Charles Sossa, Soto-Rojas, Victoria E, Soumaré, Aïcha, Sovic, Slavica, Sparboe-Nilsen, Bente, Sparrenberger, Karen, Spinelli, Angela, Spiroski, Igor, Staessen, Jan A, Stamm, Hanspeter, Stathopoulou, Maria G, Staub, Kaspar, Stavreski, Bill, Steene-Johannessen, Jostein, Stehle, Peter, Stein, Aryeh D, Stergiou, George S, Stessman, Jochanan, Stevanovic, Ranko, Stieber, Jutta, Stöckl, Dori, Stocks, Tanja, Stokwiszewski, Jakub, Stoyanova, Ekaterina, Stratton, Gareth, Stronks, Karien, Strufaldi, Maria Wany, Sturua, Lela, Suárez-Medina, Ramón, Suka, Machi, Sun, Chien-An, Sundström, Johan, Sung, Yn-Tz, Sunyer, Jordi, Suriyawongpaisal, Paibul, Swinburn, Boyd A, Sy, Rody G, Syddall, Holly E, Sylva, René Charle, Szklo, Moyse, Szponar, Lucjan, Tai, E Shyong, Tammesoo, Mari-Lii, Tamosiunas, Abdona, Tan, Eng Joo, Tang, Xun, Tanrygulyyeva, Maya, Tanser, Frank, Tao, Yong, Tarawneh, Mohammed Rasoul, Tarp, Jakob, Tarqui-Mamani, Carolina B, Braunerová, Radka Taxová, Taylor, Anne, Taylor, Julie, Tchibindat, Félicité, Tebar, William R, Tell, Grethe S, Tello, Tania, Tham, Yih Chung, Thankappan, KR, Theobald, Holger, Theodoridis, Xenophon, Thijs, Lutgarde, Thomas, Nihal, Thuesen, Betina H, Tichá, Lubica, Timmermans, Erik J, Tjonneland, Anne, Tolonen, Hanna K, Tolstrup, Janne S, Topbas, Murat, Topór-Madry, Roman, Torheim, Liv Elin, Tormo, María José, Tornaritis, Michael J, Torrent, Matie, Torres-Collado, Laura, Toselli, Stefania, Touloumi, Giota, Traissac, Pierre, Tran, Thi Tuyet-Hanh, Trichopoulos, Dimitrio, Trichopoulou, Antonia, Trinh, Oanh TH, Trivedi, Atul, Tshepo, Lechaba, Tsigga, Maria, Tsugane, Shoichiro, Tuliakova, Azaliia M, Tulloch-Reid, Marshall K, Tullu, Fikru, Tuomainen, Tomi-Pekka, Tuomilehto, Jaakko, Turley, Maria L, Twig, Gilad, Tynelius, Per, Tzotzas, Themistokli, Tzourio, Christophe, Ueda, Peter, Ugel, Eunice, Ukoli, Flora AM, Ulmer, Hanno, Unal, Belgin, Usupova, Zhamyila, Uusitalo, Hannu MT, Uysal, Nalan, Vaitkeviciute, Justina, Valdivia, Gonzalo, Vale, Susana, Valvi, Damaskini, van Dam, Rob M, Van der Heyden, Johan, van der Schouw, Yvonne T, Van Herck, Koen, Van Minh, Hoang, Van Schoor, Natasja M, van Valkengoed, Irene GM, Vanderschueren, Dirk, Vanuzzo, Diego, Varbo, Anette, Varela-Moreiras, Gregorio, Varona-Pérez, Patricia, Vasan, Senthil K, Vega, Toma, Veidebaum, Tooma, Velasquez-Melendez, Gustavo, Velika, Biruta, Veronesi, Giovanni, Verschuren, WM Monique, Victora, Cesar G, Viegi, Giovanni, Viet, Lucie, Villalpando, Salvador, Vineis, Paolo, Vioque, Jesu, Virtanen, Jyrki K, Visser, Marjolein, Visvikis-Siest, Sophie, Viswanathan, Bharathi, Vladulescu, Mihaela, Vlasoff, Tiina, Vocanec, Dorja, Vollenweider, Peter, Völzke, Henry, Voutilainen, Ari, Voutilainen, Sari, Vrijheid, Martine, Vrijkotte, Tanja GM, Wade, Alisha N, Wagner, Aline, Waldhör, Thoma, Walton, Janette, Wambiya, Elvis OA, Bebakar, Wan Mohamad Wan, Mohamud, Wan Nazaimoon Wan, de Souza Wanderley Júnior, Rildo, Wang, Ming-Dong, Wang, Ningli, Wang, Qian, Wang, Xiangjun, Wang, Ya Xing, Wang, Ying-Wei, Wannamethee, S Goya, Wareham, Nichola, Weber, Adelheid, Wedderkopp, Niel, Weerasekera, Deepa, Weghuber, Daniel, Wei, Wenbin, Weres, Aneta, Werner, Bo, Whincup, Peter H, Widhalm, Kurt, Widyahening, Indah S, Wiecek, Andrzej, Wilks, Rainford J, Willeit, Johann, Willeit, Peter, Williams, Julianne, Wilsgaard, Tom, Wojtyniak, Bogdan, Wong-McClure, Roy A, Wong, Andrew, Wong, Jyh Eiin, Wong, Tien Yin, Woo, Jean, Woodward, Mark, Wu, Frederick C, Wu, Jianfeng, Wu, Li Juan, Wu, Shouling, Xu, Haiquan, Xu, Liang, Yaacob, Nor Azwany, Yamborisut, Uruwan, Yan, Weili, Yang, Ling, Yang, Xiaoguang, Yang, Yang, Yardim, Nazan, Yaseri, Mehdi, Yasuharu, Tabara, Ye, Xingwang, Yiallouros, Panayiotis K, Yoosefi, Moein, Yoshihara, Akihiro, You, Qi Sheng, You, San-Lin, Younger-Coleman, Novie O, Md Yusof, Safiah, Yusoff, Ahmad Faudzi, Zaccagni, Luciana, Zafiropulos, Vassili, Zainuddin, Ahmad A, Zakavi, Seyed Rasoul, Zamani, Farhad, Zambon, Sabina, Zampelas, Antoni, Zamrazilová, Hana, Zapata, Maria Elisa, Zargar, Abdul Hamid, Ko Zaw, Ko, Zdrojewski, Tomasz, Zejglicova, Kristyna, Vrkic, Tajana Zeljkovic, Zeng, Yi, Zhang, Luxia, Zhang, Zhen-Yu, Zhao, Dong, Zhao, Ming-Hui, Zhao, Wenhua, Zhen, Shiqi, Zheng, Wei, Zheng, Yingfeng, Zholdin, Bekbolat, Zhou, Maigeng, Zhu, Dan, Zins, Marie, Zitt, Emanuel, Zocalo, Yanina, Cisneros, Julio Zuñiga, Zuziak, Monika, Ezzati, Majid, Filippi, Sarah, Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), Université Paris Cité (UPCité), Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - Montpellier SupAgro, and 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)
Subjects: Population -- Health aspects, Leanness, Baixo peso/Underweight, none, Double burden, alipainoisuus, tulotaso, global health, systematic analysis, Sedentary behaviors, RC1200, Prospective associations, 0302 clinical medicine, underweight, nälänhätä, Biology (General), skin and connective tissue diseases, Children, ComputingMilieux_MISCELLANEOUS, Body mass index, Human Nutrition & Health, education.field_of_study, Humane Voeding & Gezondheid, ylipaino, General Medicine, kansainvälinen vertailu, 3. Good health, World health, Medicine, A100 Pre-clinical Medicine, Population distribution, medicine.medical_specialty, QH301-705.5, Science, Socio-culturale, Nursing, Social sciences, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Thinness, SDG 3 - Good Health and Well-being, BMI, epidemiology, obesity, None, Humans, Obesidade/Obesity, SDG 2 - Zero Hunger, education, VLAG, US adults, Omvårdnad, body mass index, malnutrition, obesity, underweight, nutritional and metabolic diseases, medicine.disease, terveellisyys, Obesity, Faculdade de Ciências Sociais, Body Mass Index, Prevalence, Risk Factors, General Biochemistry, WIAS, lihavuus, RA, Demography, N.A, double burden, Settore MED/09 - Medicina Interna, alueelliset erot, Nutrition and Disease, Animal Nutrition, [SDV]Life Sciences [q-bio], Medizin, 030204 cardiovascular system & hematology, 0601 Biochemistry and Cell Biology, Change distribution of body mass index, RA0421, Voeding en Ziekte, Epidemiology, Medicine and Health Sciences, Global health, Índice de massa corporal/Body Mass Index, 030212 general & internal medicine, Underweight, painoindeksi, 2. Zero hunger, General Neuroscience, aliravitsemus, elintarvikkeet, health, Public Health, Global Health, Social Medicine and Epidemiology, Diervoeding, 3142 Public health care science, environmental and occupational health, purl.org/pe-repo/ocde/ford#3.01.03 [https], Chinese adults, pooled analysis, medicine.symptom, Diet quality, B120 Physiology, Research Article, trends, purl.org/pe-repo/ocde/ford#1.06.03 [https], prevalence, Population, Mothers, Genetics and Molecular Biology, 3121 Internal medicine, medicine, Life Science, ddc:610, 3125 Otorhinolaryngology, ophthalmology, kehonkoostumus, Nutrition, Australian adults, General Immunology and Microbiology, purl.org/pe-repo/ocde/ford#3.01.04 [https], Ciências sociais, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Malnutrition, Epidemiology and Global Health, sense organs, Estilos de Vida e Impacto na Saúde
Abstract: From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions., Wellcome Trust, Medical Research Council, peer-reviewed
Published: 2021

13. Author response: Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight

Author: Zahra Mohammadi, Abdul Basit, Helena I. S. Nogueira, Soile E. Puhakka, Hongsheng Bi, Ari Voutilainen, Davood Khalili, Bin Zhou, Dermot O'Reilly, Natascia Rinaldo, Paulo A. Lotufo, Bahareh Kheiri, Thein Thein Htay, Simona Giampaoli, Goodarz Danaei, M. Fernanda Lima-Costa, Simona Bo, Peter Schnohr, Jerzy Chudek, Francesco Panza, Ling Yang, Katia Vergetti Bloch, Vincenzo Capuano, Holly E. Syddall, Dong Zhao, Indah Suci Widyahening, Maria Lorenza Muiesan, Leng Huat Foo, Mohsen Azimi-Nezhad, Merete Osler, Laura Torres-Collado, Manu Raj, Adroaldo Cesar Araujo Gaya, Susi Kriemler, Ali Akbar Shayesteh, Aneta Grajda, Anette Varbo, Kazem Mohammad, Leila Beltrami Moreira, Shu Ti Chiou, Iuliia A Rusakova, Jyh Eiin Wong, Torben Jørgensen, Lela Sturua, Lubica Ticha, Hamid Hakimi, Hazzaa M. Al-Hazzaa, Yanina Zócalo, Freda Pitakaka, Savvas C. Savva, Rajeev Gupta, Jennifer Servais, Marie Kunešová, Johanna M. Geleijnse, Elysée Claude Bika Lele, Yannis Manios, Jorge Escobedo-de la Peña, Yufang Bi, Chinh Nguyen Huu, Sibel Gogen, Viviane Cunha Cardoso, Kristine H. Allin, Ana Azevedo, Line Tang Møllehave, Vincent Jr DeGennaro, Novie O. Younger-Coleman, Gretchen A Stevens, Dickman Gareta, Holger Theobald, Anja Schienkiewitz, Bekbolat Zholdin, Janice Luisa Lukrafka, Adela Chirita-Emandi, Ulla Roggenbuck, Kenisha Russell Jonsson, Robespierre Ribeiro, Gabriele Eiben, Eero Kajantie, Sounnia Mediene Benchekor, Fariborz Mansour-Ghanaei, Mary Simon, Prakash C. Gupta, Mohammad Esmaeel Motlagh, Emanuela Gualdi-Russo, María Elena Díaz-Sánchez, Pilar Guallar-Castillón, Bee Koon Poh, Cristina Padez, Azaliia M Tuliakova, Sarah P. Garnett, William R. Tebar, Yingfeng Zheng, Suhad Bahijri, Christina Mavrogianni, Mihaela Vladulescu, Jan A. Staessen, Paula Duarte de Oliveira, Rui Ornelas, Michael Sjöström, Charles Agyemang, Slawomir Koziel, Shohreh Naderimagham, Jari Jokelainen, Stephen T. McGarvey, Patrick Pasquet, Farnam Mohebi, Nader Saki, Aida Pilav, Azim Nejatizadeh, Marianna Noale, Habiba Ben Romdhane, Luís B. Sardinha, Laura Lauria, Jun Hata, Kodanda R Kanala, Gert B. M. Mensink, Nils Lehmann, Elio Riboli, Carolina Tarqui-Mamani, Rodrigo M. Carrillo-Larco, Rosangela Fernandes Lucena Batista, Victoria E Soto-Rojas, Luis Serra-Majem, Martina Müller-Nurasyid, Felipe Vogt Cureau, Lekhraj Rampal, Zhamilya Battakova, Ludmila Sevcikova, Suhaila Abdul Ghaffar, Fikru Tullu, Aung Soe Htet, Angel R. Gonzalez, Annette J. Dobson, Kavumpurathu Raman Thankappan, Hélène Delisle, Francisco J. Félix-Redondo, Ramón Suárez-Medina, Annika Rosengren, Sania Nishtar, Tanja G. M. Vrijkotte, Wolfgang Ahrens, Osvaldo Santos, Maria Cecília Formoso Assunção, Kazi M. Jamil, Stefano Marventano, Wenbin Wei, Norsyamlina Che Abdul Rahim, Shukri F. Mohamed, Bente Sparboe-Nilsen, Soon-Woo Park, Ana Isabel Rito, David Goltzman, W. M. 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Pérez, Vera Lanska, Tint Swe Latt, Dominique Hange, João Luiz Bastos, Eliza Markidou Ioannidou, Leticia Hernandez Cadena, Maya Tanrygulyyeva, Reza Malekzadeh, Dimitrios Poulimeneas, Pedro Ordunez, Thomas Waldhör, Ioannis Pagkalos, Carlo M. Barbagallo, Abla M. Sibai, Peter Vollenweider, Asher Fawwad, Emily Sonestedt, Elena Pahomova, Santosh K. Bhargava, Patrick Kolsteren, Aya Mostafa, Fangfang Chen, Flavio Nervi, Imre Janszky, Arvind Pandey, Renata Cifkova, Alexandre C. Pereira, Alejandro Diaz, Alireza Ansari-Moghaddam, Rachakulla Hari Kumar, Jaakko Mursu, Luis A. Moreno, Glen Gironella, Jelena Kos, Tilema Cama, Haakon E. Meyer, Jun Ma, Raphael E. Arku, Ziad Abdeen, Rusidah Selamat, Dianna J. Magliano, Jitendra Jonnagaddala, Konstantinos Gkiouras, Paul Korrovits, Paola Nardone, Paolo Vineis, Kotsedi D Monyeki, Khuong Quynh Long, Alberto Barceló, Camilla T. Damsgaard, Constance Schultsz, Frank J Rühli, Santiago F. Gomez, Tara Coppinger, Muhammad Islam, Pierre Traissac, Eleonora d'Orsi, Irfan Nuhoglu, Rui Providência, Bernard Maire, Leandra Abarca-Gómez, Sinead Brophy, Daniela Pierannunzio, Cristina Taddei, Wen-Harn Pan, Gregor Starc, Abdullah Alkandari, Saeed Dastgiri, Lien Braeckevelt, Gustavo Velasquez-Melendez, Sudhir Kowlessur, Bagher Larijani, Cynthia Robitaille, Mohamed M. Ali, Steiner Krokstad, Noor Ani Ahmad, Anar Dushpanova, Agustinus Soemantri, Susana Sans, Ionela Pascanu, Gwenaëlle Le Coroller, Inger Ariansen, Abhijit Sen, Sergej M. Ostojic, Silvana Donoso, Felix K. Assah, Juan A Rivera, Peter H. Whincup, Oana-Florentina Gheorghe-Fronea, Hanan F. Abdul Rahim, Yadlapalli S. Kusuma, Michael Knoflach, Moein Yoosefi, Cassiano Ricardo Rech, Paul Ferdinand M. Reganit, Tomi-Pekka Tuomainen, Francesco Gianfagna, Stefania Maggi, Mohammad Hossein Somi, Behrooz Hamzeh, Bethlehem D. Solomon, Herman Borghs, Zhanna Kalmatayeva, Heidi Klakk, Akram Pourshams, Naomi S. Levitt, Miquel Porta, Vesna Jureša, Alexander D. Deev, Son Thai Pham, Paula Margozzini, Silvia Bel-Serrat, Dora Romaguera, Monira Alarouj, Winsome R. Parnell, Marloes Cardol, David Faeh, Antonio Bernabe-Ortiz, Giota Touloumi, Maryam Kavousi, Sanja Musić Milanović, Jalila El Ati, Sauli Herrala, Liang Xu, Sirkka Keinänen-Kiukaanniemi, Ian Hambleton, Stefan Savin, Andre Pascal Kengne, R. Krishna Kumar, Kurt Widhalm, Marco M Ferrario, Parisa Amiri, Yi Song, Jianfeng Wu, Jeannette Klimont, Jean Ferrières, Farhad Zamani, Shina Avi, Luis Paulo Gomes Mascarenhas, Aluísio J D Barros, Reecha Sofat, Koen Van Herck, Hoang Van Minh, Enrique Gutiérrez-González, Martine Vrijheid, Susana Cararo Confortin, Antonis Zampelas, Bogdan Wojtyniak, Ausra Petrauskiene, Juha Auvinen, Maryam Sharafkhah, Emanuel Zitt, Majid Ezzati, Young-Ho Khang, Ellina Rakhimova, Magdalena Klimek, Luís Lopes, Erkin M. Mirrakhimov, Maria Lc Iurilli, Günay Can, Mark Woodward, Esther Lopez-Garcia, Mauro Virgílio Gomes de Barros, Ahmed A. Madar, Rainford J. Wilks, Shoaib Afzal, Melanie J. Cowan, Gareth Stratton, Eduardo Salazar Martinez, Sameer Narake, Norie Sawada, Li Juan Wu, Adrian Richter, Licia Iacoviello, Hanno Ulmer, Deepak Amarapurkar, Mohsen Ibrahim, Hamed Pouraram, Massimo Salvetti, Hung-Kwan So, Yonghua Hu, Lars Ängquist, Thi Tuyet-Hanh Tran, Charles Lunogelo, Sabina Zambon, Angelika Schaffrath Rosario, Lauren Lissner, Kamarul Imran Musa, Deepa Weerasekera, Bihungum Bista, Takafumi Ishida, Ekaterina Chikova-Iscener, Mirjam M. Heinen, Tazeen H. Jafar, Semánová Csilla, Raija Korpelainen, Edward W. Gregg, Laura Gutierrez, Victor M. Herrera, Aristides M. Machado-Rodrigues, Fatemeh Malekzadeh, Shouling Wu, Jennifer L. Baker, Clicerio González-Villalpando, Irene G. M. van Valkengoed, Anna Fijałkowska, Meghnath Dhimal, Murat Topbaş, George Moschonis, Robert Eggertsen, Quang Ngoc Nguyen, Janette Walton, Elnaz Faramarzi, Nasheeta Peer, Radka Taxová Braunerová, Harald Geiger, Morteza Shamshirgaran, Lela Shengelia, María Ángeles Dal Re Saavedra, Khem Bahadur Karki, Timothy J. Key, Maria G. Grammatikopoulou, Susana Vale, Bernhard O. Boehm, Songhomitra Panda-Jonas, Iveta Pudule, Elisabete Ramos, Lacramioara Aurelia Brinduse, Paul H. Lee, Terence W O'Neill, Javad Aghazadeh-Attari, Margus Punab, Bojan Jelaković, Eliza Cinteza, Ha Tp Do, and Alison J. Hayes
Subjects: education.field_of_study, business.industry, Population, Distribution (economics), medicine.disease, Obesity, Geography, medicine, Underweight, medicine.symptom, education, business, Body mass index, Demography
Published: 2020

14. Analysis of individual families implicates noncoding DNA variation and multiple biological pathways in Alzheimer’s disease risk

Author: Richard Mayeux, Alzheimer’s Disease Sequencing, Margaret A. Pericak-Vance, Rafael A. Nafikov, Ellen M. Wijsman, Cornelia M. van Duijn, Patrick A. Navas, J. C. Bis, Mohamad Saad, Andrea R. V. R. Horimoto, Badri N. Vardarajan, Debby W. Tsuang, Harkirat Sohi, Tyler R. Day, Gary W. Beecham, Sandra Barral, Elizabeth E. Blue, Eden R. Martin, Timothy A. Thornton, and Alejandro Q. Nato
Subjects: Genetics, Epidemiology, Health Policy, Disease, Biology, Noncoding DNA, Biological pathway, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Variation (linguistics), Developmental Neuroscience, Disease risk, Neurology (clinical), Geriatrics and Gerontology
Published: 2020

15. Characterizing the genetic architecture of Parkinson’s disease in Latinos

Author: Andrea Rivera-Valdivia, Carlos Roberto de Mello Rieder, Víctor Raggio, Emily Mason, Miguel Inca-Martinez, William Fernandez, Angel C. Medina, Paul Cannon, Henrique Ballalai Ferraz, Andres G. Lescano, Pilar Mazzetti, Karl Heilbron, Sonia Moreno, Gonzalo Arboleda, Humberto Arboleda, Timothy D. O’Connor, Carlos E. Arboleda-Bustos, Vanderci Borges, Timothy A. Thornton, Ignacio F. Mata, Bruno Lopes Santos-Lobato, Pedro Chana-Cuevas, Carlos Velez-Pardo, Vitor Tumas, Elena Dieguez, Cyrus P. Zabetian, Douglas Loesch, Francisco Lopera, Marlene Jimenez-Del-Rio, Luis Torres, Dora Yearout, Mario Cornejo-Olivas, Elif Irem Sarihan, Carlos Cosentino, Andrea R. V. R. Horimoto, Elison Sarapura-Castro, and Artur F. Schumacher-Schuh
Subjects: Genetics, education.field_of_study, Chromosome 3, Population, Cohort, Genetic admixture, Locus (genetics), Genome-wide association study, Biology, education, Genetic architecture, Genetic association
Abstract: To date, over 90 Parkinson’s disease (PD) risk variants have been reported from genome-wide association studies (GWAS). However, these GWAS efforts have been limited to individuals of European and East Asian ancestry. We performed the first GWAS of Latino PD patients from South America, comparing 807 cases against 690 controls followed by association testing of suggestive loci in a replication cohort of 1,234 cases and 439,522 controls. We demonstrated that SNCA plays a significant role in PD etiology in a Latino cohort and identified a suggestive locus near NRROS on chromosome 3 that appeared to be driven by Peruvian subjects. We also characterized the overlap of PD genetic architecture between Europeans and Latinos with a replication of significant variants identified by Nalls et al. in their 2019 GWAS1, finding 80% concordance in direction of effect. We then leveraged the population history of Latinos via admixture mapping, identifying a significant locus on chromosome 14 in a joint test of ancestries, driven by the Native American ancestral background, and a significant locus on chromosome 6 in our test of African ancestry, containing the genes STXBP6 and RPS6KA2, respectively. Ultimately, our work reflects the most comprehensive characterization of PD genetic architecture in Latinos to date.
Published: 2020

16. Multi-ancestry genome-wide gene-sleep interactions identify novel loci for blood pressure

Author: Lisa W. Martin, Tuomas O. Kilpeläinen, Xiuqing Guo, Kurt Lohman, Ching-Ti Liu, Jerome I. Rotter, Pirjo Komulainen, Lili Milani, Ilja M. Nolte, Yuri Milaneschi, Andres Metspalu, Yii-Der Ida Chen, Tõnu Esko, Jovia L. Nierenberg, Mika Kähönen, Marjan Ilkov, Dennis O. Mook-Kanamori, Karen Schwander, W. James Gauderman, Hanfei Xu, Vilmundur Gudnason, Alisa K. Manning, Gudny Eiriksdottir, David R. Hillman, Elise Lim, Hugues Aschard, John M. Starr, Michael R. Brown, Alanna C. Morrison, Eric Boerwinkle, Stefan Weiss, Maris Alver, Konstantin Strauch, Thomas Meitinger, Tuomo Rankinen, Timo A. Lakka, Harold Snieder, Stephen S. Rich, Yun Ju Sung, Diana van Heemst, Wanqing Wen, Marcus Dörr, Peter J. van der Most, Terho Lehtimäki, Nora Franceschini, Treva Rice, Amy R. Bentley, Dan E. Arking, Susan Redline, Nienke R. Biermasz, Sarah E. Harris, Melanie Waldenberger, Claude Bouchard, M. Arfan Ikram, Walter Palmas, Lynne E. Wagenknecht, Bruce M. Psaty, Daniel Levy, Cornelia M. van Duijn, Joshua C. Bis, Kelly A. Hall, José Eduardo Krieger, Tanika N. Kelly, Kari E. North, Brigitte Kühnel, Phyllis C. Zee, Melissa A. Richard, Lyle J. Palmer, Till Roenneberg, Alexandre C. Pereira, Yongmei Liu, Andrea R. V. R. Horimoto, Jie Yao, Han Chen, Jiang He, Pamela J. Schreiner, Patricia B. Munroe, Wei Zheng, Charles Kooperberg, Paul S. de Vries, Ana Barac, Rainer Rauramaa, Leo-Pekka Lyytikäinen, James M. Shikany, Brian E. Cade, Christian Gieger, Stephen Sidney, Alan B. Zonderman, Tamar Sofer, Chuan Gao, Thomas W. Winkler, Xiao-Ou Shu, Ian J. Deary, Uwe Völker, RJ Waken, Heming Wang, Myriam Fornage, Brenda W.J.H. Penninx, Gregory P. Wilson, Dina Vojinovic, Robert B. Wallace, Kenneth Rice, Ervin R. Fox, Jeffrey R. O'Connell, Annemarie I. Luik, Traci M. Bartz, Xiaofeng Zhu, Najaf Amin, Nicholette D. Palmer, Sami Heikkinen, Kumaraswamynaidu Chitrala, Raymond Noordam, Jiwon Lee, André G. Uitterlinden, Sutapa Mukherjee, Hans J. Grabe, Mario Sims, Sina A. Gharib, Daniel J. Gottlieb, Dabeeru C. Rao, Annette Peters, Reedik Mägi, Solomon K. Musani, Michele K. Evans, Lenore J. Launer, Harvard Medical School [Boston] (HMS), Broad Institute [Cambridge], Harvard University-Massachusetts Institute of Technology (MIT), Hallym University, Department of Educational Psychology and Counseling, National Taiwan Normal University (NTNU), Département de Biologie Computationnelle - Department of Computational Biology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Leiden University Medical Center (LUMC), Universiteit Leiden, This project was supported by the US National Heart, Lung, and Blood Institute (NHLBI) R01HL118305. HW and SR were supported by NHLBI R35HL135818. BEC was supported by NHLBI K01HL135405. ARB was supported by the Intramural Research Program of the National Institutes of Health in the Center for Research on Genomics and Global Health (CRGGH). The CRGGH is supported by the National Human Genome Research Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the Center for Information Technology, and the Office of the Director at the National Institutes of Health (1ZIAHG200362). D.v.H. was supported by the European Commission funded project HUMAN (Health-2013-INNOVATION-1-602757). The CHARGE cohorts were supported in part by NHLBI infrastructure grant HL105756. Study-specific acknowledgments can be found in the Supplementary Notes., European Project: 602757,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,HUMAN(2013), Life Course Epidemiology (LCE), Epidemiology, Radiology & Nuclear Medicine, Internal Medicine, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, APH - Digital Health, Massachusetts Institute of Technology (MIT)-Harvard University [Cambridge], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Tampere University, Department of Clinical Chemistry, Clinical Medicine, and Department of Clinical Physiology and Nuclear Medicine
Subjects: 0301 basic medicine, Mean arterial pressure, Diastole, Blood Pressure, Biology, 3121 Internal medicine, Genome, Polymorphism, Single Nucleotide, Elevated blood, 3124 Neurology and psychiatry, Article, Cellular and Molecular Neuroscience, 03 medical and health sciences, TRPC3, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Humans, Molecular Biology, Gene, 030304 developmental biology, Genetics, 0303 health sciences, [STAT.AP]Statistics [stat]/Applications [stat.AP], Short sleep, Sleep in non-human animals, Pulse pressure, Psychiatry and Mental health, 030104 developmental biology, Blood pressure, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Genetic Loci, Hypertension, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 3111 Biomedicine, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Sleep, [STAT.ME]Statistics [stat]/Methodology [stat.ME], 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Long and short sleep duration are associated with elevated blood pressure (BP), possibly through effects on molecular pathways that influence neuroendocrine and vascular systems. To gain new insights into the genetic basis of sleep-related BP variation, we performed genome-wide gene by short or long sleep duration interaction analyses on four BP traits (systolic BP, diastolic BP, mean arterial pressure, and pulse pressure) across five ancestry groups using 1 degree of freedom (1df) interaction and 2df joint tests. Primary multi-ancestry analyses in 62,969 individuals in stage 1 identified 3 novel loci that were replicated in an additional 59,296 individuals in stage 2, including rs7955964 (FIGNL2/ANKRD33) showing significant 1df interactions with long sleep duration and rs73493041 (SNORA26/C9orf170) and rs10406644 (KCTD15/LSM14A) showing significant 1df interactions with short sleep duration (Pint < 5×10−8). Secondary ancestry-specific two-stage analyses and combined stage 1 and 2 analyses additionally identified 23 novel loci that need external replication, including 3 and 5 loci showing significant 1df interactions with long and short sleep duration, respectively (Pint < 5×10−8). Multiple genes mapped to our 26 novel loci have known functions in sleep-wake regulation, nervous and cardiometabolic systems. We also identified new gene by long sleep interactions near five known BP loci (≤1Mb) including NME7, FAM208A, MKLN1, CEP164, and RGL3/ELAVL3 (Pint < 5×10−8). This study indicates that sleep and primary mechanisms regulating BP may interact to elevate BP level, suggesting novel insights into sleep-related BP regulation.
Published: 2020

17. Genome-wide Analysis of Copy Number Variation in Latin American Parkinson's Disease Patients

Author: Artur F. Schumacher-Schuh, Dora Yearout, Sonia Moreno, Andrea Rivera-Valdivia, Gonzalo Arboleda, Elena Dieguez, Vanderci Borges, Elison Sarapura-Castro, Lisa-Marie Niestroj, Carlos Roberto de Mello Rieder, Víctor Raggio, Timothy A. Thornton, Pilar Mazzetti, Carlos Velez-Pardo, Cyrus P. Zabetian, Humberto Arboleda, Pedro Chana-Cuevas, Miguel Inca-Martinez, Henrique Ballalai Ferraz, Eduardo Pérez-Palma, Ignacio F. Mata, Timothy D. O’Connor, William Fernandez, Vitor Tumas, Andres G. Lescano, Bruno Lopes Santos-Lobato, Carlos Cosentino, Marlene Jimenez-Del-Rio, Dennis Lal, Carlos E. Arboleda-Bustos, Douglas Loesch, Francisco Lopera, Luis Torres, Elif Irem Sarihan, Mario Cornejo-Olivas, and Andrea R. V. R. Horimoto
Subjects: Oncology, medicine.medical_specialty, education.field_of_study, Parkinson's disease, business.industry, Population, Genome wide analysis, Disease, Odds ratio, medicine.disease, Internal medicine, Cohort, medicine, Copy-number variation, education, business, Genotyping
Abstract: Background: Parkinson's disease is the second most common neurodegenerative disorder and affects people from all ethnic backgrounds, yet little is known about the genetics of Parkinson's disease in non-European populations. In addition, the overall identification of copy number variants at a genome-wide level has been understudied in Parkinson's disease patients. Objectives: To understand the genome-wide burden of copy number variants in Latinos and its association with Parkinson's disease. Methods: We used genome-wide genotyping data from 747 Parkinson's disease patients and 632 ancestry matched controls from the Latin American Research Consortium on the Genetics of Parkinson's disease. Results: Genome-wide copy number burden analysis showed no difference between patients vs. controls, whereas patients were significantly enriched for copy number variants overlapping known Parkinson's disease genes compared to controls (Odds Ratio: 3.97 [1.69 - 10.5], P = 0.018). PARK2 showed the strongest copy number burden, with 20 copy number variant carriers. These patients presented an earlier age of disease onset compared to patients with other copy number variants (median age at onset: 31 years vs. 57 years, P = 7.46 x 10-7). Conclusions: We found that Parkinson's disease patients are significantly enriched with copy number variants affecting known Parkinson's disease genes. We also identified that out of 250 patients with early-onset disease, 5.6% carried a copy number variant on PARK2 in our cohort. Our study is the first to analyze genome-wide copy number variants association in Latino Parkinson's disease patients and provides insights about this complex disease in this understudied population.
Published: 2020

18. Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci

Author: Yongmei Liu, Tuomas O. Kilpeläinen, Kenneth Rice, Ching-Ti Liu, Jin-Fang Chai, Donna K. Arnett, Dhananjay Vaidya, Nicholette D. Palmer, Lili Milani, Yuri Milaneschi, Leo-Pekka Lyytikäinen, Colleen M. Sitlani, Richard S. Cooper, Gudny Eiriksdottir, Daniel Levy, Jerome I. Rotter, Lihua Wang, Sven Bergmann, Yih Chung Tham, Thomas Meitinger, Lynne E. Wagenknecht, Virginia Fisher, Babatunde L. Salako, Vilmundur Gudnason, Bamidele O. Tayo, Caizheng Yu, Barry I. Freedman, Muhammad Riaz, Kaare Christensen, Ulrich Broeckel, W. James Gauderman, Massimiliano Cocca, Eric Boerwinkle, Meian He, Rob M. van Dam, M. Arfan Ikram, Lisa de las Fuentes, Jiang He, Aldi T. Kraja, Nancy L. Pedersen, Albert V. Smith, Woon-Puay Koh, Bernardo L. Horta, He Gao, Traci M. Bartz, Mike A. Nalls, Federica Laguzzi, Raymond Noordam, Paul M. Ridker, Tien Yin Wong, Patricia B. Munroe, Paul S. de Vries, Adolfo Correa, Maris Alver, Dan E. Arking, Colin A. McKenzie, John M. Starr, Chi Charles Gu, Dongfeng Gu, Stefan Weiss, Patricia A. Peyser, Jessica D. Faul, Xu Chen, Jill M. Norris, Patrik K. E. Magnusson, Tamar Sofer, Ioanna Ntalla, Xiuqing Guo, Paul Elliott, Lawrence F. Bielak, Konstantin Strauch, Xueling Sim, Norihiro Kato, Evangelos Evangelou, Ilja M. Nolte, Steven C. Hunt, Mario Sims, Giorgia Girotto, Chuan Gao, Pamela J. Schreiner, Philippe Froguel, Archie Campbell, Xiao-Ou Shu, Claude Bouchard, Kurt Lohman, David R. Weir, José Eduardo Krieger, Yii-Der Ida Chen, Rainer Rauramaa, Walter Palmas, Cornelia M. van Duijn, James M. Shikany, Michael M. Province, Jennifer A. Smith, Wei Zheng, Xiaofeng Zhu, Jianjun Liu, Ozren Polasek, Alexandre C. Pereira, Diane M. Becker, Kari E. North, Salman M. Tajuddin, Deng Xuan, Leslie J. Raffel, Jie Yao, Astrid Petersmann, Ervin F. Fox, Mark J. Caulfield, Daniel I. Chasman, Jasmin Divers, Claudia P. Cabrera, Rico Rueedi, M. Yldau van der Ende, Carl D. Langefeld, Mika Kähönen, Terrence Forrester, Tangchun Wu, Harold Snieder, Caroline Hayward, Tamara B. Harris, Fang-Chi Hsu, Helen R. Warren, Brenda W.J.H. Penninx, Chiea Chuen Khor, Ruifang Li-Gao, Changwei Li, Sami Heikkinen, Jeffrey R. O'Connell, Christian Gieger, Michele K. Evans, Ching-Yu Cheng, Jingjing Liang, Stephen B. Kritchevsky, Gregory L. Burke, Donald W. Bowden, Alexander Teumer, Marcus Dörr, Alanna C. Morrison, Jian-Min Yuan, Annette Peters, Dennis O. Mook-Kanamori, Pedro Marques-Vidal, Pirjo Komulainen, Lisa R. Yanek, Melanie Waldenberger, Alisa K. Manning, Charles N. Rotimi, Chew-Kiat Heng, Tõnu Esko, Franco Giulianini, Miao Li Chee, Treva Rice, David J. Porteous, Yechiel Friedlander, Bing Yu, Myriam Fornage, Karin Leander, Dina Vojinovic, Sharon L.R. Kardia, Xiaoyin Li, Najaf Amin, Karen Schwander, Thomas T. Perls, Oscar Leonel Rueda-Ochoa, Erin B. Ware, Ya Xing Wang, Sandosh Padmanabhan, H. Janaka de Silva, André G. Uitterlinden, Rajkumar Dorajoo, Bruna Gigante, Jennifer A. Brody, Paolo Gasparini, Maryam Kavousi, Wanqing Wen, Stephen Sidney, Alan B. Zonderman, Michael R. Brown, Tuomo Rankinen, Timo A. Lakka, Yun Ju Sung, Alaitz Poveda, Bruce M. Psaty, Terho Lehtimäki, Tanika N. Kelly, Igor Rudan, Brigitte Kühnel, Christopher P. Nelson, John M. C. Connell, Mickaël Canouil, Niek Verweij, Thomas W. Winkler, Ian J. Deary, Marco Brumat, Yize Li, Fumihiko Takeuchi, Wei Zhao, Andres Metspalu, Marguerite R. Irvin, David C. Liewald, Pim van der Harst, Hugues Aschard, Candace M. Kammerer, Melissa A. Richard, Adesola Ogunniyi, Wen Bin Wei, Morris A. Swertz, Fernando Pires Hartwig, Dabeeru C. Rao, Reedik Mägi, Solomon K. Musani, Mathilde Boissel, Jonathan Marten, Nilesh J. Samani, Amy R. Bentley, Sarah E. Harris, Charumathi Sabanayagam, Mary F. Feitosa, Jost B. Jonas, Andrea R. V. R. Horimoto, Paul W. Franks, E. Shyong Tai, Medical Research Council (MRC), de las Fuentes, L., Sung, Y. J., Noordam, R., Winkler, T., Feitosa, M. F., Schwander, K., Bentley, A. R., Brown, M. R., Guo, X., Manning, A., Chasman, D. I., Aschard, H., Bartz, T. M., Bielak, L. F., Campbell, A., Cheng, C. -Y., Dorajoo, R., Hartwig, F. P., Horimoto, A. R. V. R., Li, C., Li-Gao, R., Liu, Y., Marten, J., Musani, S. K., Ntalla, I., Rankinen, T., Richard, M., Sim, X., Smith, A. V., Tajuddin, S. M., Tayo, B. O., Vojinovic, D., Warren, H. R., Xuan, D., Alver, M., Boissel, M., Chai, J. -F., Chen, X., Christensen, K., Divers, J., Evangelou, E., Gao, C., Girotto, G., Harris, S. E., He, M., Hsu, F. -C., Kuhnel, B., Laguzzi, F., Li, X., Lyytikainen, L. -P., Nolte, I. M., Poveda, A., Rauramaa, R., Riaz, M., Rueedi, R., Shu, X. -O., Snieder, H., Sofer, T., Takeuchi, F., Verweij, N., Ware, E. B., Weiss, S., Yanek, L. R., Amin, N., Arking, D. E., Arnett, D. K., Bergmann, S., Boerwinkle, E., Brody, J. A., Broeckel, U., Brumat, M., Burke, G., Cabrera, C. P., Canouil, M., Chee, M. L., Chen, Y. -D. I., Cocca, M., Connell, J., de Silva, H. J., de Vries, P. S., Eiriksdottir, G., Faul, J. D., Fisher, V., Forrester, T., Fox, E. F., Friedlander, Y., Gao, H., Gigante, B., Giulianini, F., Gu, C. C., Gu, D., Harris, T. B., He, J., Heikkinen, S., Heng, C. -K., Hunt, S., Ikram, M. A., Irvin, M. R., Kahonen, M., Kavousi, M., Khor, C. C., Kilpelainen, T. O., Koh, W. -P., Komulainen, P., Kraja, A. T., Krieger, J. E., Langefeld, C. D., Li, Y., Liang, J., Liewald, D. C. M., Liu, C. -T., Liu, J., Lohman, K. K., Magi, R., Mckenzie, C. A., Meitinger, T., Metspalu, A., Milaneschi, Y., Milani, L., Mook-Kanamori, D. O., Nalls, M. A., Nelson, C. P., Norris, J. M., O'Connell, J., Ogunniyi, A., Padmanabhan, S., Palmer, N. D., Pedersen, N. L., Perls, T., Peters, A., Petersmann, A., Peyser, P. A., Polasek, O., Porteous, D. J., Raffel, L. J., Rice, T. K., Rotter, J. I., Rudan, I., Rueda-Ochoa, O. -L., Sabanayagam, C., Salako, B. L., Schreiner, P. J., Shikany, J. M., Sidney, S. S., Sims, M., Sitlani, C. M., Smith, J. A., Starr, J. M., Strauch, K., Swertz, M. A., Teumer, A., Tham, Y. C., Uitterlinden, A. G., Vaidya, D., van der Ende, M. Y., Waldenberger, M., Wang, L., Wang, Y. -X., Wei, W. -B., Weir, D. R., Wen, W., Yao, J., Yu, B., Yu, C., Yuan, J. -M., Zhao, W., Zonderman, A. B., Becker, D. M., Bowden, D. W., Deary, I. J., Dorr, M., Esko, T., Freedman, B. I., Froguel, P., Gasparini, P., Gieger, C., Jonas, J. B., Kammerer, C. M., Kato, N., Lakka, T. A., Leander, K., Lehtimaki, T., Magnusson, P. K. E., Marques-Vidal, P., Penninx, B. W. J. H., Samani, N. J., van der Harst, P., Wagenknecht, L. E., Wu, T., Zheng, W., Zhu, X., Bouchard, C., Cooper, R. S., Correa, A., Evans, M. K., Gudnason, V., Hayward, C., Horta, B. L., Kelly, T. N., Kritchevsky, S. B., Levy, D., Palmas, W. R., Pereira, A. C., Province, M. M., Psaty, B. M., Ridker, P. M., Rotimi, C. N., Tai, E. S., van Dam, R. M., van Duijn, C. M., Wong, T. Y., Rice, K., Gauderman, W. J., Morrison, A. C., North, K. E., Kardia, S. L. R., Caulfield, M. J., Elliott, P., Munroe, P. B., Franks, P. W., Rao, D. C., Fornage, M., Washington University in Saint Louis (WUSTL), Leiden University Medical Center (LUMC), University of Regensburg, Washington University School of Medicine in St. Louis, National Institutes of Health [Bethesda] (NIH), Harbor UCLA Medical Center [Torrance, Ca.], Massachusetts General Hospital [Boston], Département de Biologie Computationnelle - Department of Computational Biology, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Harvard School of Public Health, Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), 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-Centre National de la Recherche Scientifique (CNRS), The University of Texas Health Science Center at Houston (UTHealth), Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, APH - Digital Health, Universiteit Leiden, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Lifelines Cohort Study, Epidemiology, Radiology & Nuclear Medicine, Internal Medicine, Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), and Cardiovascular Centre (CVC)
Subjects: 0301 basic medicine, CORONARY-HEART-DISEASE, SOCIOECONOMIC-STATUS, RISK-FACTORS, CARDIOVASCULAR-DISEASE, ESSENTIAL-HYPERTENSION, C825T POLYMORPHISM, SOCIAL-CLASS, ASSOCIATION, EXPRESSION, VARIANTS, Blood Pressure, Genome, 0302 clinical medicine, 11 Medical and Health Sciences, Genetics, Psychiatry, [STAT.AP]Statistics [stat]/Applications [stat.AP], 17 Psychology and Cognitive Sciences, Psychiatry and Mental health, Meta-analysis, Hypertension, [STAT.ME]Statistics [stat]/Methodology [stat.ME], Life Sciences & Biomedicine, GNB3, Biochemistry & Molecular Biology, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, Lifelines Cohort Study, SDG 3 - Good Health and Well-being, Humans, Risk factor, Molecular Biology, Gene, Science & Technology, Neurosciences, Epistasis, Genetic, 06 Biological Sciences, Genetic architecture, Educational attainment, 030104 developmental biology, Blood pressure, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Genetic Loci, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurosciences & Neurology, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Blood Pressure/genetics, Genome-Wide Association Study, Hypertension/genetics, 030217 neurology & neurosurgery
Abstract: Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, "Some College" (yes/no) and "Graduated College" (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10 -8 ). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.
Published: 2020

19. Association of the genetic ancestry with resistant hypertension in the ReHOT (Resistant Hypertension Optimal Treatment) randomized study

Author: Carolina Tosin Bueno, Eduardo M. Krieger, Hadassa Campos Santos, José Eduardo Krieger, Alexandre C. Pereira, Luz Marina Gomez Gomez, Paulo Caleb Junior Lima Santos, and Andrea R. V. R. Horimoto
Subjects: Genetic Markers, Male, medicine.medical_specialty, Genetic testing, medicine.medical_treatment, Genetic genealogy, lcsh:Medicine, Black People, Coronary Vasospasm, 030204 cardiovascular system & hematology, Polymorphism, Single Nucleotide, Article, White People, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Multicenter trial, Genetic variation, medicine, Humans, Prospective Studies, 030212 general & internal medicine, lcsh:Science, Genetic Association Studies, Multidisciplinary, business.industry, Indians, South American, lcsh:R, Cardiovascular genetics, Middle Aged, Clinical trial, Blood pressure, Genetic marker, Hypertension, lcsh:Q, Female, Diuretic, business, Brazil
Abstract: Resistant hypertension (RH) is defined as uncontrolled blood pressure despite treatment with three or more antihypertensive medications, including, if tolerated, a diuretic in adequate doses. It has been widely known that race is associated with blood pressure control. However, intense debate persists as to whether this is solely explained by unadjusted socioeconomical variables or genetic variation. In this scenario, the main aim was to evaluate the association between genetic ancestry and resistant hypertension in a large sample from a multicenter trial of stage II hypertension, the ReHOT study. Samples from 1,358 patients were analyzed, of which 167 were defined as resistant hypertensive. Genetic ancestry was defined using a panel of 192 polymorphic markers. The genetic ancestry was similar in resistant (52.0% European, 36.7% African and 11.3% Amerindian) and nonresistant hypertensive patients (54.0% European, 34.4% African and 11.6% Amerindian) (p > 0.05). However, we observed a statistically suggestive association of African ancestry with resistant hypertension in brown patient group. In conclusion, increased African genetic ancestry was not associated with RH in Brazilian patients from a prospective randomized hypertension clinical trial.
Published: 2020

20. Cardiometabolic risk factors correlated with the incidence of dysglycaemia in a Brazilian normoglycaemic sample: the Baependi Heart Study cohort

Author: Camila Maciel de Oliveira, Danilo Alvares, Luciane Viater Tureck, Chunyu Liu, Andrea R. V. R. Horimoto, José Eduardo Krieger, Rafael de Oliveira Alvim, and Alexandre C. Pereira
Subjects: medicine.medical_specialty, Waist, Endocrinology, Diabetes and Metabolism, Population, Short Report, Impaired glucose tolerance, Dysglycaemia, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Prediabetes, education, lcsh:RC620-627, Cardiovascular risk factors, education.field_of_study, business.industry, Incidence (epidemiology), Cohort, Baependi Heart Study cohort, Impaired fasting glucose, medicine.disease, lcsh:Nutritional diseases. Deficiency diseases, Longitudinal study, business, Brazil
Abstract: Background Dysglycaemia is defined by elevated glucose levels in the blood, commonly characterized by impaired fasting glucose, impaired glucose tolerance, elevated glycated haemoglobin, or diabetes mellitus (DM) diagnosis. The abnormal levels of glucose may occur many years before DM, a condition known as prediabetes, which is correlated with comorbidities such as cardiovascular diseases. Therefore, the aim of this study was to investigate the incidence of prediabetic dysglycaemia and its relationship with cardiometabolic risk factors at a 5-year follow-up, based on an initially normoglycaemic sample in the Baependi Heart Study cohort. Methods The data used comes from the Baependi Heart Study cohort, which consists of two periods: cycle 1 (2005–2006) and cycle 2 (2010–2013). For this study, we excluded those who had fasting blood glucose ≥ 100 mg/dL or were taking anti-diabetic medications at baseline, and those that had diabetes diagnosed in cycle 2. Mixed-effects logistic regression models were used to assess the association between cardiometabolic risk factors and the incidence of dysglycaemia, including a familiar random effect such as a cluster. Results The incidence of prediabetic dysglycaemia was 12.8%, and it did not differ between men and women (14.4% and 11.6%, respectively). Two models were analysed to investigate the relationship between cardiometabolic risk factors and the occurrence of prediabetic dysglycaemia. The model that better explained the occurrence of dysglycaemia over the 5 years, after correction, included the waist circumference (WC) (measures and Δ), systolic blood pressure (SBP), HDL-c levels, and age. Although sex was not associated with the incidence of dysglycaemia, women and men showed differences in cardiometabolic risk factors related to glucose impairment: men who developed dysglycaemia showed, in parallel, higher LDL-c levels, TC/HDL-c ratio and DBP measurements; while these parameters remained similar between women who developed dysglycaemia and dysglycaemia-free women, after 5 years. Conclusions In an initially normoglycaemic sample of a highly mixed population living in a traditional Brazilian lifestyle, important cardiometabolic risk factors were associated with the occurrence of prediabetic dysglycaemia, and this relationship appeared to be more important in men. These results provide important insights about cardiovascular risk in prediabetic individuals.
Published: 2020

21. Relationship between marital status and incidence of type 2 diabetes mellitus in a Brazilian rural population: The Baependi Heart Study

Author: Danilo Alvares, Andrea R. V. R. Horimoto, Alexandre C. Pereira, José Eduardo Krieger, Luciane Viater Tureck, Chunyu Liu, Rafael de Oliveira Alvim, Camila Maciel de Oliveira, and Mercedes Balcells
Subjects: Blood Glucose, Male, Rural Population, endocrine system diseases, Epidemiology, Type 2 diabetes, Logistic regression, Geographical locations, Endocrinology, Medical Conditions, 0302 clinical medicine, Risk Factors, Medicine and Health Sciences, Public and Occupational Health, 030212 general & internal medicine, Multidisciplinary, Incidence, Incidence (epidemiology), Heart, Middle Aged, Socioeconomic Aspects of Health, Type 2 Diabetes, Hypertension, Marital status, Medicine, Female, Anatomy, Behavioral and Social Aspects of Health, Rural population, Brazil, Research Article, Adult, medicine.medical_specialty, Endocrine Disorders, Science, 030209 endocrinology & metabolism, Education, 03 medical and health sciences, Diabetes mellitus, Diabetes Mellitus, medicine, Humans, Obesity, Marital Status, business.industry, Racial Groups, Biology and Life Sciences, Type 2 Diabetes Mellitus, nutritional and metabolic diseases, South America, medicine.disease, Health Care, Logistic Models, Diabetes Mellitus, Type 2, Metabolic Disorders, Medical Risk Factors, Cardiovascular Anatomy, People and places, business, Demography
Abstract: Many factors influence the incidence of type 2 diabetes mellitus (T2DM). Here, we investigated the associations between socio-demographic characteristics and familial history with the 5-year incidence of T2DM in a family-based study conducted in Brazil. T2DM was defined as baseline fasting blood glucose ≥ 126 mg/dL or the use of any hypoglycaemic drug. We excluded individuals with T2DM at baseline or if they did not attend two examination cycles. After exclusions, we evaluated a sample of 1,125 participants, part of the Baependi Heart Study (BHS). Mixed-effects logistic regression models were used to assess T2DM incident given different characteristics. At the 5-year follow-up, the incidence of T2DM was 6.7% (7.2% men and 6.3% women). After adjusting for age, sex, and education status, the model that combined marital and occupation status, skin color, and familial history of T2DM provided the best prediction for T2DM incidence. Only marital status was independently associated with T2DM incidence. Individuals that remained married, despite having significantly increased their weight, were significantly less likely to develop diabetes than their divorced counterparts.
Published: 2020

22. Metabolic syndrome alters relationships between cardiometabolic variables, cognition and white matter hyperintensity load

Author: Annette Sterr, M. von Schantz, Andrea R. V. R. Horimoto, André B. Negrão, Simon Evans, Sabine Pompéia, José Eduardo Krieger, Rafael de Oliveira Alvim, Erkan Alkan, Homero Vallada, Tâmara P. Taporoski, and Alexandre C. Pereira
Subjects: 0301 basic medicine, Male, lcsh:Medicine, B100, Neuropsychological Tests, behavioral disciplines and activities, Article, 03 medical and health sciences, 0302 clinical medicine, Cognition, Risk Factors, mental disorders, medicine, Humans, Effects of sleep deprivation on cognitive performance, lcsh:Science, Cognitive reserve, Aged, Aged, 80 and over, Metabolic Syndrome, Multidisciplinary, Recall, business.industry, lcsh:R, Stepwise regression, Middle Aged, medicine.disease, Magnetic Resonance Imaging, White Matter, C800, B900, 030104 developmental biology, Blood pressure, White matter hyperintensity, Cardiovascular Diseases, lcsh:Q, Female, Metabolic syndrome, business, Energy Metabolism, 030217 neurology & neurosurgery, Biomarkers, Clinical psychology
Abstract: Cardiometabolic risk factors influence white matter hyperintensity (WMH) development: in metabolic syndrome (MetS), higher WMH load is often reported but the relationships between specific cardiometabolic variables, WMH load and cognitive performance are uncertain. We investigated these in a Brazilian sample (aged 50–85) with (N = 61) and without (N = 103) MetS. Stepwise regression models identified effects of cardiometabolic and demographic variables on WMH load (from FLAIR MRI) and verbal recall performance. WMH volume was greater in MetS, but verbal recall performance was not impaired. Age showed the strongest relationship with WMH load. Across all participants, systolic blood pressure (SBP) and fasting blood glucose were also contributors, and WMH volume was negatively associated with verbal recall performance. In non-MetS, higher HbA1c, SBP, and number of MetS components were linked to poorer recall performance while higher triglyceride levels appeared to be protective. In MetS only, these relationships were absent but education exerted a strongly protective effect on recall performance. Thus, results support MetS as a construct: the clustering of cardiometabolic variables in MetS alters their individual relationships with cognition; instead, MetS is characterised by a greater reliance on cognitive reserve mechanisms. In non-MetS, strategies to control HbA1c and SBP should be prioritised as these have the largest impact on cognition.
Published: 2019

23. P032 Data from the brazilian baependi heart study cohort yield new insights into the genetic epidemiology of insomnia

Author: Luz Marina Gomez Gomez, Felipe Beijamini, Sabrina S. Ahmed, Tâmara P. Taporoski, Annette Sterr, André B. Negrão, Alexandre C. Pereira, Malcolm von Schantz, Francieli S. Ruiz, Kristen L. Knutson, and Andrea R. V. R. Horimoto
Subjects: education.field_of_study, business.industry, Population, Genome-wide association study, Regression analysis, Heritability, Genetic epidemiology, Cohort, Insomnia, medicine, medicine.symptom, education, business, Demography, Genetic association
Abstract: Introduction Insomnia significantly impacts lifetime morbidity and thus has substantial socioeconomic costs. In developed, high-income countries insomnia prevalence is increasing. However, little is known about insomnia in less urbanised, lower-income populations. Baependi is a Brazilian rural town, which has been shown to maintain sleep cycles synchronised to natural daylight, in spite of electrification. We aimed to investigate the components of insomnia in the family-based Baependi Heart Study cohort, using the Insomnia Severity Index (ISI) questionnaire. Methods and materials Descriptive analysis was performed on data collected from the Baependi population (n=1,202) using R software. Heritability analysis was calculated using polygenic mixed modelling. Genome-wide association analysis (GWAS) was subsequently performed on the Baependi data, in order to interrogate for associations with polymorphisms previously related with insomnia symptoms (n= 811). Results Descriptive regression analysis categorised 7.6% of the participants as suffering from ‘clinical insomnia’ based on their ISI scores, with an average total score of 6.5±5.0 (SD). Heritability of ISI score, based on the best-fit model adjusted for sex, age, education, and depression, was 19%. GWAS yielded four associations of genome-wide significance with single-nucleotide polymorphisms (SNP) rs869481, rs62037617 and rs3747579, which are located in the CORO7 gene, and rs3789038, located on the neighbouring HMOX2 gene on chromosome 16. Conclusion This is one of the first studies of ISI score distribution in a general population. The heritability value observed is consistent with previously published literature, which have used different measures of insomnia symptoms. In addition, this is the first reported GWAS analysis for ISI score, identifying the first significant genome-wide genetic associations of ISI score. Thus, this study confirms the reliability and suitability of ISI as a measure for genetic studies in population. Acknowledgements This study was supported by the Santander Universities Researcher Mobility Award and CNPq (PVE 400791/2014-5).
Published: 2019

24. MTRR rs326119 polymorphism is associated with plasma concentrations of homocysteine and cobalamin, but not with congenital heart disease or coronary atherosclerosis in Brazilian patients

Author: Carolina Tosin Bueno, Paulo Caleb Junior Lima Santos, Antonio A Morandini-Filho, José Eduardo Krieger, Alexandre C. Pereira, Melanie Horita, Pedro A. Lemos, and Andrea R. V. R. Horimoto
Subjects: 0301 basic medicine, medicine.medical_specialty, lcsh:Diseases of the circulatory (Cardiovascular) system, Heart disease, Homocysteine, rs326119, 030204 cardiovascular system & hematology, Gastroenterology, Cobalamin, Article, MTRR gene, DOENÇAS CONGÊNITAS, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Genotype, medicine, Vitamin B12, Genotyping, Coronary atherosclerosis, Congenital heart disease, Genetics, business.industry, medicine.disease, MTRR, 030104 developmental biology, chemistry, lcsh:RC666-701, Cardiology and Cardiovascular Medicine, business
Abstract: Background Differences in the distribution of the MTRR rs326119 polymorphism (c.56+781 A>C) between patients with congenital heart disease (CHD) and controls have been described in Chinese individuals. The association is thought to be due to deregulation of homocysteine-cobalamin pathways. This has not been replicated in other populations. The primary objective of this study was to assess the influence of the MTRR rs326119 polymorphism on biochemical parameters of vitamin B12 metabolism, coronary lesions, and congenital heart disease in Brazilian subjects. Methods We selected 722 patients with CHD, 1432 patients who underwent coronary angiography, and 156 blood donors. Genotyping for the MTRR polymorphism was evaluated by high-resolution melting analysis, and biochemical tests of vitamin B12 metabolism were measured. Results Subjects carrying the AC or CC genotypes had higher homocysteine concentrations (9.7±0.4μmol/L and 10.1±0.6μmol/L) and lower cobalamin concentrations (260.5±13.3pmol/L and 275.6±19.9pmol/L) compared with the subjects carrying the AA genotype (8.7±0.5μmol/L and 304.8±14.7pmol/L), respectively. A multiple linear regression model also identified a significant association between the number of C variant alleles with the concentrations of homocysteine and cobalamin. Nonetheless, the allelic and genotypic distributions for MTRR rs326119 were not associated with CHD or coronary atherosclerosis in the studied samples. Conclusion Our findings indicate that the MTRR rs326119 variant might be a genetic marker associated with homocysteine and cobalamin concentrations, but not a strong risk factor for CHD or coronary atherosclerosis in the Brazilian population.
Published: 2017

25. Heritability of arterial stiffness in a Brazilian population

Author: Camila Maciel de Oliveira, José Eduardo Krieger, Luiz Aparecido Bortolotto, Andrea R. V. R. Horimoto, Alexandre C. Pereira, and Rafael de Oliveira Alvim
Subjects: Adult, Male, musculoskeletal diseases, 0301 basic medicine, medicine.medical_specialty, Pathology, animal structures, Adolescent, Physiology, macromolecular substances, Disease, Pulse Wave Analysis, 030204 cardiovascular system & hematology, Young Adult, 03 medical and health sciences, Vascular Stiffness, 0302 clinical medicine, Internal medicine, Internal Medicine, Humans, Medicine, Pulse wave velocity, Aged, Aged, 80 and over, Models, Statistical, business.industry, Age Factors, technology, industry, and agriculture, Family aggregation, Middle Aged, Heritability, equipment and supplies, medicine.disease, Phenotype, 030104 developmental biology, Blood pressure, Hypertension, Cardiology, Arterial stiffness, Female, Aortic stiffness, Brazilian population, Cardiology and Cardiovascular Medicine, business, Brazil
Abstract: Increased arterial stiffness is an important determinant of cardiovascular disease risk. In addition, it has been recognized that arterial stiffness has familial aggregation; however, there are no studies involving Brazilian families. Thus, the aim of this study was to evaluate the heritability of arterial stiffness in a Brazilian population.In this study, 1675 eligible individuals (both sexes and aged 18-102 years) were distributed in 125 families resident in the municipality of Baependi, a city located in the southeast of Brazil. Carotid-femoral pulse wave velocity (PWV) was measured with a noninvasive automatic device (Complior; Artech Medical, Pantin, France). Variance component approaches, implemented in the SOLAR computer package (San Antonio, Texas, USA), were applied to estimate the heritability of the studied phenotype under different statistical models.Heritability estimates for carotid-femoral PWV stratified by age ranging from 11 to 35% (higher in individuals aged ≤45 years and lower in individuals aged 18-102 years). Age and hypertension showed significant effects on the PWV trait and significantly affect heritability estimates in all models.We conclude that the heritability of carotid-femoral PWV in a Brazilian population is intermediate, and therefore genetic studies evolving arterial stiffness phenotypes should be encouraged.
Published: 2017

26. A multi-ancestry genome-wide study incorporating gene–smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure

Author: Bamidele O. Tayo, RJ Waken, Mario Sims, Diane M. Becker, Tõnu Esko, Yingchang Lu, Pamela J. Schreiner, Antonietta Robino, Anne U. Jackson, H. Janaka de Silva, Peter J. van der Most, Archie Campbell, Ozren Polasek, Salman M. Tajuddin, Jing Hua Zhao, Barbara V. Howard, Saima Afaq, Vilmundur Gudnason, Lynda M. Rose, Francis S. Collins, Massimiliano Cocca, Ruth J. F. Loos, Yii-Der Ida Chen, W. James Gauderman, Jaspal S. Kooner, Lawrence F. Bielak, Ulrich Broeckel, Anuradhani Kasturiratne, Melissa A. Richard, Tomohiro Katsuya, Nicola D. Kerrison, Tin Aung, Lisa de las Fuentes, Lynne E. Wagenknecht, Oscar H. Franco, Yongmei Liu, Eric Boerwinkle, Nana Matoba, Saskia P. Hagenaars, Rob M. van Dam, Tibor V. Varga, Nilesh J. Samani, Tangchun Wu, Thomas H. Mosley, Caroline Hayward, Joseph H. Lee, Frida Renström, Tamara B. Harris, Alena Stančáková, Adesola Ogunniyi, Wen Bin Wei, Lenore J. Launer, Marcus Dörr, Xiuqing Guo, Jennifer A. Smith, Terho Lehtimäki, Dan E. Arking, Fang-Chi Hsu, Karin Leander, Martin Farrall, Konstantin Strauch, Albert V. Smith, Richard S. Cooper, Chiea Chuen Khor, Changwei Li, James E. Hixson, Sami Heikkinen, David R. Weir, Pirjo Komulainen, Renée de Mutsert, Raymond Noordam, Ubaydah Nasri, Paul M. Ridker, C. Charles Gu, Tamuno Alfred, Jerome I. Rotter, Nora Franceschini, Nita G. Forouhi, Lihua Wang, Alanna C. Morrison, Jian-Min Yuan, Ching-Yu Cheng, Peter S. Braund, Paul Elliott, Gregory P. Wilson, Jianjun Liu, Xiaofeng Zhu, Markku Laakso, Christian Gieger, Yukihide Momozawa, Rainer Rettig, Carsten Oliver Schmidt, Amy R. Bentley, Wei Zhao, Ioanna Ntalla, Kenneth Rice, Yoichiro Kamatani, Andres Metspalu, Helen R. Warren, Yechiel Friedlander, Susan Redline, Kurt Lohman, Cornelia M. van Duijn, Aravinda Chakravarti, Traci M. Bartz, Sarah E. Harris, Yih Chung Tham, He Gao, Mike A. Nalls, Mathilde Boissel, Donna K. Arnett, Harold Snieder, James S. Pankow, Babatunde L. Salako, Laura J. Bierut, Tin Louie, Albertine J. Oldehinkel, Xueling Sim, Thomas Meitinger, Maris Alver, Claudia Langenberg, Stephen B. Kritchevsky, Norihiro Kato, Evangelos Evangelou, Philippe Froguel, Alexandre C. Pereira, Michael R. Brown, Karen Schwander, Charles Kooperberg, Blair H. Smith, Annette Peters, Fernando Pires Hartwig, Yanhua Zhou, Jie Yao, Alisa K. Manning, Keng-Hung Lin, Dennis O. Mook-Kanamori, Ervin R. Fox, Tuomo Rankinen, Timo A. Lakka, Charles N. Rotimi, Nicholette D. Palmer, Jiang He, Nicholas J. Wareham, Jingmin Liu, Yun Ju Sung, Cathy C. Laurie, Donald W. Bowden, Yong-Bing Xiang, Lisa R. Yanek, B. Kuhnel, Nancy L. Pedersen, Yajuan Wang, Ananda R. Wickremasinghe, Jonathan Marten, Yi-Jen Hung, Dabeeru C. Rao, Bernardo L. Horta, Joel D. Kaufman, Barry I. Freedman, Chuan Gao, Olli T. Raitakari, Reedik Mägi, Solomon K. Musani, Albert Hofman, Wanqing Wen, Heming Wang, Xiao-Ou Shu, Y Liu, Mark J. Caulfield, Meian He, Daniel I. Chasman, Carl D. Langefeld, Charumathi Sabanayagam, Bruce M. Psaty, Jasmin Divers, R. Graham Barr, Chew-Kiat Heng, Stella Aslibekyan, John M. Starr, Stefan Weiss, Anuj Goel, Tuomas O. Kilpeläinen, Terrence Forrester, Mary F. Feitosa, Jost B. Jonas, Kae-Woei Liang, Colleen M. Sitlani, Daniel Levy, Marie Loh, Qing Duan, Aldi T. Kraja, Tien Yin Wong, Myriam Fornage, Andrea R. V. R. Horimoto, Michele K. Evans, David J. Porteous, Dina Vojinovic, Hua Tang, Michael A. Province, Ching-Ti Liu, Rainer Rauramaa, William R. Scott, Cora E. Lewis, Charles B. Eaton, Sharon L.R. Kardia, Michael Boehnke, James Scott, Colin A McKenzie, Jin-Fang Chai, Woon-Puay Koh, Yucheng Jia, Claude Bouchard, Peter S. Sever, Koichi Matsuda, Najaf Amin, Ulf de Faire, Walter Palmas, André G. Uitterlinden, Thomas T. Perls, Erin B. Ware, Wayne Huey-Herng Sheu, Michiaki Kubo, Ya Xing Wang, Hugh Watkins, Steven C. Hunt, Weihua Zhang, Johanna Kuusisto, Lili Milani, Rajkumar Dorajoo, Georg Ehret, L. Adrienne Cupples, Franco Giulianini, Zoltán Kutalik, Jose E Krieger, Kevin Sandow, Bruna Gigante, Alexander P. Reiner, Preeti Gupta, Heikki A. Koistinen, Treva Rice, Patricia B. Munroe, Wen-Jane Lee, Jennifer A. Brody, Paolo Gasparini, Paul W. Franks, Yik Ying Teo, Leo-Pekka Lyytikäinen, Thomas W. Winkler, Patricia A. Peyser, Ian J. Deary, Jessica D. Faul, Sing Hui Lim, Fumihiko Takeuchi, Xu Chen, Brian E. Cade, Patrik K. E. Magnusson, John C. Chambers, Tamar Sofer, E. Shyong Tai, Candace M Kammerer, Mary K. Wojczynski, Pim van der Harst, Marzyeh Amini, Jennifer G. Robinson, Erwin P. Bottinger, Alan B. Zonderman, Benjamin Lehne, M. Waldenberger, Jeffrey R. O'Connell, Hugues Aschard, Ilaria Gandin, Kent D. Taylor, Igor Rudan, Christopher P. Nelson, John M. C. Connell, Jian'an Luan, Mickaël Canouil, Robert A. Scott, Yize Li, Marguerite R. Irvin, Sung, Yun Ju, de Las Fuentes, Lisa, Winkler, Thomas W, Chasman, Daniel I, Bentley, Amy R, Kraja, Aldi T, Ntalla, Ioanna, Warren, Helen R, Guo, Xiuqing, Schwander, Karen, Manning, Alisa K, Brown, Michael R, Aschard, Hugue, Feitosa, Mary F, Franceschini, Nora, Lu, Yingchang, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Marten, Jonathan, Musani, Solomon K, Kilpeläinen, Tuomas O, Richard, Melissa A, Aslibekyan, Stella, Bartz, Traci M, Dorajoo, Rajkumar, Li, Changwei, Liu, Yongmei, Rankinen, Tuomo, Smith, Albert Vernon, Tajuddin, Salman M, Tayo, Bamidele O, Zhao, Wei, Zhou, Yanhua, Matoba, Nana, Sofer, Tamar, Alver, Mari, Amini, Marzyeh, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gandin, Ilaria, Gao, Chuan, Giulianini, Franco, Goel, Anuj, Harris, Sarah E, Hartwig, Fernando P, He, Meian, Horimoto, Andrea R V R, Hsu, Fang-Chi, Jackson, Anne U, Kammerer, Candace M, Kasturiratne, Anuradhani, Komulainen, Pirjo, Kühnel, Brigitte, Leander, Karin, Lee, Wen-Jane, Lin, Keng-Hung, Luan, Jian'An, Lyytikäinen, Leo-Pekka, Mckenzie, Colin A, Nelson, Christopher P, Noordam, Raymond, Scott, Robert A, Sheu, Wayne H H, Stančáková, Alena, Takeuchi, Fumihiko, van der Most, Peter J, Varga, Tibor V, Waken, Robert J, Wang, Heming, Wang, Yajuan, Ware, Erin B, Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R, Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Alfred, Tamuno, Amin, Najaf, Arking, Dan E, Aung, Tin, Barr, R Graham, Bielak, Lawrence F, Boerwinkle, Eric, Bottinger, Erwin P, Braund, Peter S, Brody, Jennifer A, Broeckel, Ulrich, Cade, Brian, Campbell, Archie, Canouil, Mickaël, Chakravarti, Aravinda, Cocca, Massimiliano, Collins, Francis S, Connell, John M, de Mutsert, Renée, de Silva, H Janaka, Dörr, Marcu, Duan, Qing, Eaton, Charles B, Ehret, Georg, Evangelou, Evangelo, Faul, Jessica D, Forouhi, Nita G, Franco, Oscar H, Friedlander, Yechiel, Gao, He, Gigante, Bruna, Gu, C Charle, Gupta, Preeti, Hagenaars, Saskia P, Harris, Tamara B, He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hofman, Albert, Howard, Barbara V, Hunt, Steven C, Irvin, Marguerite R, Jia, Yucheng, Katsuya, Tomohiro, Kaufman, Joel, Kerrison, Nicola D, Khor, Chiea Chuen, Koh, Woon-Puay, Koistinen, Heikki A, Kooperberg, Charles B, Krieger, Jose E, Kubo, Michiaki, Kutalik, Zoltan, Kuusisto, Johanna, Lakka, Timo A, Langefeld, Carl D, Langenberg, Claudia, Launer, Lenore J, Lee, Joseph H, Lehne, Benjamin, Levy, Daniel, Lewis, Cora E, Li, Yize, Lim, Sing Hui, Liu, Ching-Ti, Liu, Jianjun, Liu, Jingmin, Liu, Yeheng, Loh, Marie, Lohman, Kurt K, Louie, Tin, Mägi, Reedik, Matsuda, Koichi, Meitinger, Thoma, Metspalu, Andre, Milani, Lili, Momozawa, Yukihide, Mosley, Thomas H, Nalls, Mike A, Nasri, Ubaydah, O'Connell, Jeff R, Ogunniyi, Adesola, Palmas, Walter R, Palmer, Nicholette D, Pankow, James S, Pedersen, Nancy L, Peters, Annette, Peyser, Patricia A, Polasek, Ozren, Porteous, David, Raitakari, Olli T, Renström, Frida, Rice, Treva K, Ridker, Paul M, Robino, Antonietta, Robinson, Jennifer G, Rose, Lynda M, Rudan, Igor, Sabanayagam, Charumathi, Salako, Babatunde L, Sandow, Kevin, Schmidt, Carsten O, Schreiner, Pamela J, Scott, William R, Sever, Peter, Sims, Mario, Sitlani, Colleen M, Smith, Blair H, Smith, Jennifer A, Snieder, Harold, Starr, John M, Strauch, Konstantin, Tang, Hua, Taylor, Kent D, Teo, Yik Ying, Tham, Yih Chung, Uitterlinden, André G, Waldenberger, Melanie, Wang, Lihua, Wang, Ya Xing, Wei, Wen Bin, Wilson, Gregory, Wojczynski, Mary K, Xiang, Yong-Bing, Yao, Jie, Yuan, Jian-Min, Zonderman, Alan B, Becker, Diane M, Boehnke, Michael, Bowden, Donald W, Chambers, John C, Chen, Yii-Der Ida, Weir, David R, de Faire, Ulf, Deary, Ian J, Esko, Tõnu, Farrall, Martin, Forrester, Terrence, Freedman, Barry I, Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Horta, Bernardo Lessa, Hung, Yi-Jen, Jonas, Jost Bruno, Kato, Norihiro, Kooner, Jaspal S, Laakso, Markku, Lehtimäki, Terho, Liang, Kae-Woei, Magnusson, Patrik K E, Oldehinkel, Albertine J, Pereira, Alexandre C, Perls, Thoma, Rauramaa, Rainer, Redline, Susan, Rettig, Rainer, Samani, Nilesh J, Scott, Jame, Shu, Xiao-Ou, van der Harst, Pim, Wagenknecht, Lynne E, Wareham, Nicholas J, Watkins, Hugh, Wickremasinghe, Ananda R, Wu, Tangchun, Kamatani, Yoichiro, Laurie, Cathy C, Bouchard, Claude, Cooper, Richard S, Evans, Michele K, Gudnason, Vilmundur, Hixson, Jame, Kardia, Sharon L R, Kritchevsky, Stephen B, Psaty, Bruce M, van Dam, Rob M, Arnett, Donna K, Mook-Kanamori, Dennis O, Fornage, Myriam, Fox, Ervin R, Hayward, Caroline, van Duijn, Cornelia M, Tai, E Shyong, Wong, Tien Yin, Loos, Ruth J F, Reiner, Alex P, Rotimi, Charles N, Bierut, Laura J, Zhu, Xiaofeng, Cupples, L Adrienne, Province, Michael A, Rotter, Jerome I, Franks, Paul W, Rice, Kenneth, Elliott, Paul, Caulfield, Mark J, Gauderman, W Jame, Munroe, Patricia B, Rao, Dabeeru C, Morrison, Alanna C, Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Brigham and Women's Hospital [Boston], Queen Mary University of London (QMUL), Harbor UCLA Medical Center [Torrance, Ca.], Département de Biologie Computationnelle - Department of Computational Biology, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Harvard School of Public Health, European Genomic Institute for Diabetes - FR 3508 (EGID), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), The University of Texas Health Science Center at Houston (UTHealth), U.S. National Heart, Lung, and Blood Institute (NHLBI) (K25HL121091 to Y.J.S.), National Institutes of Health (R01HL118305), We thank anonymous reviewers for critical reading and providing constructive and insightful comments, which substantially improved the article. This project, like several other projects, was carried out as part of the CHARGE Gene–Lifestyle Interactions Working Group., Conflict of Interest statement. The authors declare no competing financial interests except for the following: B.M.P. serves on the Data and Safety Monitoring Board of a clinical trial funded by the manufacturer (Zoll LifeCor) and on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson, O.H.F. received grants from Metagenics (on women’s health and epigenetics) and from Nestle (on child health), L.J.B. is listed as an inventor on Issued U.S. Patent 8,080,371,‘Markers for Addiction’ covering the use of certain SNPs in determining the diagnosis, prognosis and treatment of addiction, P.S. has received research awards from Pfizer Inc, J.B.J. is a consultant for Mundipharma Co. (Cambridge, UK), Patent holder with Biocompatibles UK Ltd (Franham, Surrey, UK) (title: treatment of eye diseases using encapsulated cells encoding and secreting neuroprotective factor and/or anti-angiogenic factor, Patent number: 20120263794) and Patent application with University of Heidelberg (Heidelberg, Germany) (title: agents for use in the therapeutic or prophylactic treatment of myopia or hyperopia, Europäische Patentanmeldung 15000771.4), P.W.F. has been a paid consultant for Eli Lilly and Sanofi Aventis and has received research support from several pharmaceutical companies as part of a European Union Innovative Medicines Initiative project, M.A.N.'s participation is supported by a consulting contract between Data Tecnica International and the National Institute on Aging, National Institutes of Health, Bethesda, MD, USA, M.A.N. also consults for Illumina Inc, the Michael J. Fox Foundation and University of California Healthcare among others, and M.J. C. is chief scientist for Genomics England, a UK government company., Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 (EGID), 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-Centre National de la Recherche Scientifique (CNRS), Epidemiology, Internal Medicine, Life Course Epidemiology (LCE), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Cardiovascular Centre (CVC), University Management, Department of Medicine, University of Helsinki, HUS Abdominal Center, Endokrinologian yksikkö, Marten, Jonathan [0000-0001-6916-2014], Luan, Jian'an [0000-0003-3137-6337], Zhao, Jing Hua [0000-0003-4930-3582], Forouhi, Nita [0000-0002-5041-248X], Langenberg, Claudia [0000-0002-5017-7344], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, and Medical Research Council (MRC)
Subjects: Male, Receptors, Vasopressin, multi-ancestry, Genome-wide association study, Blood Pressure, HYDROCARBON RECEPTOR AHR, 030204 cardiovascular system & hematology, Antiporters, gene-smoking interaction, 0302 clinical medicine, Polymorphism (computer science), genome-wide study, Ethnicity, OXIDATIVE STRESS, Association Studies Article, 11 Medical and Health Sciences, Genetics (clinical), Genetics & Heredity, Genetics, ddc:616, Aged, 80 and over, 0303 health sciences, [STAT.AP]Statistics [stat]/Applications [stat.AP], DEPENDENT HYPERTENSION, CARDIOVASCULAR RISK, Smoking, 1184 Genetics, developmental biology, physiology, General Medicine, ASSOCIATION, Middle Aged, Caspase 9, 3. Good health, Pulse pressure, ENVIRONMENT INTERACTION, Sulfate Transporters, T-CADHERIN, Hypertension, Female, Life Sciences & Biomedicine, [STAT.ME]Statistics [stat]/Methodology [stat.ME], Adult, Biochemistry & Molecular Biology, Mean arterial pressure, Adolescent, Diastole, Biology, elevated blood pressure, gene-smoking interactions, 03 medical and health sciences, Young Adult, Insulin resistance, Lifelines Cohort Study, medicine, Humans, Arterial Pressure, Molecular Biology, METAANALYSIS, 030304 developmental biology, Aged, Science & Technology, Polymorphism, Genetic, Tumor Suppressor Proteins, Racial Groups, Membrane Proteins, 06 Biological Sciences, SYSTOLIC BLOOD-PRESSURE, BODY-MASS INDEX, medicine.disease, Blood pressure, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Heart failure, 1182 Biochemistry, cell and molecular biology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Gene-Environment Interaction, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Genome-Wide Association Study
Abstract: Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene–smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene–smoking interaction analysis and 38 were newly identified (P
Published: 2019

27. Multi-ancestry analysis of gene-sleep interactions in 126,926 individuals identifies multiple novel blood lipid loci that contribute to our understanding of sleep-associated adverse blood lipid profile

Author: Patricia A. Peyser, Yuri Milaneschi, Marjan Ilkov, Xiuqing Guo, Brian E. Cade, Tamar Sofer, Hugues Aschard, Kent D. Taylor, Vilmundur Gudnason, Vincent Laville, Eric Boerwinkle, Thomas W. Winkler, Thomas Meitinger, Amy R. Bentley, Lynne E. Wagenknecht, Susan Redline, Jingmin Liu, Meian He, Till Roenneberg, Christian Gieger, Diana van Heemst, Nienke R. Biermasz, Stephen B. Kritchevsky, Henry Völzke, Georg Homuth, Pedro Marques-Vidal, Ashley van der Spek, Tanika N. Kelly, José Haba-Rubio, Heming Wang, Maxime M. Bos, Brigitte Kühnel, Han Chen, Peter Vollenweider, Jonathan Marten, Ruth J. F. Loos, Correa Adolfo, Raymond Noordam, Olli T. Raitakari, W. James Gauderman, Minjung Kho, Michele K. Evans, Tamara B. Harris, Robert B. Wallance, Rainer Rauramaa, Maria E. Graff, José Eduardo Krieger, Alexandre C. Pereira, Konstantin Strauch, Jerome I. Rotter, Ervin F. Fox, Mary F. Feitosa, Nora Franceschini, Hans J. Grabe, Kurt Lohman, Mario Sims, Caizheng Yu, Melissa A. Richard, Paul Elliott, Zhe Wang, Stephen Sidney, Alan B. Zonderman, Alexander P. Reiner, Daniel J. Gottlieb, M. A. Province, Pamela J. Schreiner, Stefan Weiss, Raphael Heinzer, Brenda W.J.H. Penninx, Diane M. Becker, Tangchun Wu, Tõnu Esko, Lisa W. Martin, Changwei Li, Wei Zheng, Evangelos Evangelou, Jeffrey R. O'Connell, Patrick C.N. Rensen, Claude Bouchard, James E. Hixson, Elise Lim, Morris A. Swertz, Michael R. Brown, Annette Peters, Sami Heikkinen, Jiwon Lee, Tuomo Rankinen, Timo A. Lakka, Ilja M. Nolte, Stephen S. Rich, Yun Ju Sung, Terho Lehtimäki, André G. Uitterlinden, Cornelia M. van Duijn, Stella Aslibekyan, Ko Willems van Dijk, Alisa K. Manning, Bruce M. Psaty, Kari E. North, Salman M. Tajuddin, Myriam Fornage, Christie M. Ballantyne, Dina Vojinovic, Pirjo Komulainen, Andres Metspalu, Najaf Amin, Traci M. Bartz, Mike A. Nalls, Maris Alver, Dennis O. Mook-Kanamori, Lisa R. Yanek, James M. Shikany, Yong-Bing Xiang, L.F. Bielak, Charles N. Rotimi, Treva Rice, Xiaofeng Zhu, Sharon L.R. Kardia, Yongmei Liu, L. Adrienne Cupples, Kenneth Rice, Donna K. Arnett, Annemarie I. Luik, Niki Dimou, Nicholette D. Palmer, Charles Kooperberg, M. Arfan Ikram, Lisa de las Fuentes, Harold Snieder, Leo-Pekka Lyytikäinen, Chuan Gao, Xiao-Ou Shu, Tuomas O. Kilpeläinen, Ching-Ti Liu, Alanna C. Morrison, Gudny Eiriksdottir, Colleen M. Sitlani, Melanie Waldenberger, Aldi T. Kraja, Paul S. de Vries, Andrea R. V. R. Horimoto, Sina A. Gharib, Karen Schwander, Dabeeru C. Rao, Wanqing Wen, Reedik Mägi, Solomon K. Musani, and Patricia B. Munroe
Subjects: Genetics, 0303 health sciences, medicine.diagnostic_test, Triglyceride, PCSK9, Blood lipids, Biology, Explained variation, Sleep in non-human animals, Biological pathway, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, chemistry, medicine, lipids (amino acids, peptides, and proteins), Lipid profile, Gene, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract: Both short and long sleep are associated with an adverse lipid profile, likely through different biological pathways. To provide new insights in the biology of sleep-associated adverse lipid profile, we conducted multi-ancestry genome-wide sleep-SNP interaction analyses on three lipid traits (HDL-c, LDL-c and triglycerides). In the total study sample (discovery + replication) of 126,926 individuals from 5 different ancestry groups, when considering either long or short total sleep time interactions in joint analyses, we identified 49 novel lipid loci, and 10 additional novel lipid loci in a restricted sample of European-ancestry cohorts. In addition, we identified new gene-sleep interactions for known lipid loci such asLPLandPCSK9. The novel gene-sleep interactions had a modest explained variance in lipid levels: most notable, gene-short-sleep interactions explained 4.25% of the variance in triglyceride concentration. Collectively, these findings contribute to our understanding of the biological mechanisms involved in sleep-associated adverse lipid profiles.
Published: 2019
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28. Heritability and Sex-Specific Genetic Effects of Self-Reported Physical Activity in a Brazilian Highly Admixed Population

Author: Rafael de Oliveira Alvim, Júlia Maria Pavan Soler, Alexandre C. Pereira, Jean Michel Rocha Sampaio Leite, and Andrea R. V. R. Horimoto
Subjects: Male, Waist, Population, Inheritance Patterns, Biology, Article, Body Mass Index, 03 medical and health sciences, Population Groups, Genetic variation, Genetics, medicine, Humans, education, Exercise, Genetics (clinical), Genetic Association Studies, 030304 developmental biology, 0303 health sciences, education.field_of_study, Sex Characteristics, Models, Genetic, Depression, 030305 genetics & heredity, Smoking, Genetic Variation, Heritability, medicine.disease, Obesity, Genetic architecture, Phenotype, REGRESSÃO LINEAR, Body Constitution, Female, Self Report, Sedentary Behavior, Body mass index, Brazil, Demography, Sex characteristics
Abstract: Introduction: The engagement in sports or habitual physical activity (PA) has shown an extensive protective role against multiple diseases such as cancer, obesity, and many others. Additionally, PA has also a significant impact on life quality, since it aids with managing stress, preserving cognitive function and memory, and preventing fractures in the elderly. Objective: Considering there has been multiple evidence showing that genetic variation underpins variation of PA-related traits, we aimed to estimate the heritability (h2) of these phenotypes in a sample from the Brazilian population and assess whether males and females differ in relation to those estimates. Methods: 2,027 participants from a highly admixed population from Baependi, MG, Brazil, had information regarding their PA and sedentary behavior (SB) phenotypes collected through a questionnaire (IPAQ-SF). After data cleaning and transformation procedures, we obtained four variables to be evaluated: total PA (TPA MET), walking time, (WK MET), moderate-vigorous PA (MVPA MET), and SB. A model selection procedure was performed using a single-step covariate inclusion approach. We tested for BMI, waist, hip and neck circumferences, smoking, and depression separately, and performed correlation tests among covariates. Linear mixed models, selection procedure, and the variance components approach to estimate h2 were implemented using SOLAR-Eclipse 8.3.1. Results: We obtained estimates of 0.221, 0.109, 0.226, and 0 for TPA MET, WK MET, MVPA MET, and SB, respectively. We found evidence for gene-sex interactions, with males having higher sex-specific heritabilities than females for TPA MET and MVPA MET. In addition, we found higher estimates of the genetic variance component in males than females for most phenotypes. Discussion/Conclusion: The heritability estimates presented in this work show a moderate heritable set of genetic factors affecting PA in a sample from the Brazilian population. The evaluation of the genetic variance component suggests segregating genetic factors in male individuals are more heterogeneous, which can explain why men globally tend to need to practice more intense PA than women to achieve similar health benefits. Hence, these findings have significant implications for the understanding of the genetic architecture of PA and might aid to promote health in the future.
Published: 2019

29. Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity

Author: Michael R. Brown, Christian Gieger, André G. Uitterlinden, Diana van Heemst, Alison D. Murray, Stephen B. Kritchevsky, Timo A. Lakka, Karen Schwander, Federica Laguzzi, Stephen S. Rich, Rajkumar Dorajoo, Yun Ju Sung, Xiaofeng Zhu, Hugues Aschard, Jing Hua Zhao, Gregory P. Wilson, Kenneth Rice, Barbara Sternfeld, Kent D. Taylor, Paul Elliott, Ei-Ei Khaing Nang, Ilja M. Nolte, Heather M. Stringham, Bruce M. Psaty, Heming Wang, Tangchun Wu, Caroline Hayward, Vilmundur Gudnason, Fernando Pires Hartwig, Paolo Gasparini, Jingjing Liang, Neil Risch, Albertine J. Oldehinkel, Ani Manichaikul, Tibor V. Varga, Michael Y. Tsai, Niek Verweij, Xueling Sim, Norihiro Kato, Evangelos Evangelou, Philippe Froguel, Xiuqing Guo, Traci M. Bartz, Nicholette D. Palmer, Woon-Puay Koh, Rozenn N. Lemaitre, Caizheng Yu, Mike A. Nalls, Mariaelisa Graff, Eric Boerwinkle, Dabeeru C. Rao, Thomas Meitinger, Virginia Fisher, Mario Sims, Charles Kooperberg, Carl D. Langefeld, Jaakko Tuomilehto, Reedik Mägi, Wei Zhao, Wanqing Wen, Donna K. Arnett, Ervin R. Fox, Lynda M. Rose, Maris Alver, Ayse Demirkan, Solomon K. Musani, Dennis O. Mook-Kanamori, Andres Metspalu, Jerome I. Rotter, Barry I. Freedman, Jiang He, Hermina Jakupović, Steven C. Hunt, Marco Brumat, Maria Pina Concas, Rob M. van Dam, Rico Rueedi, Jonathan Marten, Chi Charles Gu, Tõnu Esko, Peter Vollenweider, Zoltán Kutalik, Olli T. Raitakari, Ya X. Wang, Yong-Bing Xiang, Pamela J. Schreiner, Antonietta Robino, Tanika N. Kelly, Igor Rudan, Mathilde Boissel, Claudia Langenberg, Yii-Der Ida Chen, Anne U. Jackson, Lawrence F. Bielak, Brenda W.J.H. Penninx, Brigitte Kühnel, Christopher P. Nelson, Konstantin Strauch, Albert V. Smith, Daniel I. Chasman, Jasmin Divers, Lisa R. Yanek, M. Arfan Ikram, Melissa A. Richard, Nilesh J. Samani, Lisa de las Fuentes, H. Janaka de Silva, Jana V. van Vliet-Ostaptchouk, Yongmei Liu, Peter J. van der Most, Fang-Chi Hsu, Jeffrey R. O'Connell, Alexandre C. Pereira, Raymond Noordam, Changwei Li, Jie Yao, Trudy Voortman, Zhe Wang, Thomas H. Mosley, Diane M. Becker, Charles N. Rotimi, Sami Heikkinen, Archie Campbell, John M. C. Connell, Lenore J. Launer, Hua Tang, Rainer Rauramaa, Ruth J. F. Loos, Pirjo Komulainen, Amy R. Bentley, Patrik Wennberg, Chew-Kiat Heng, Kari E. North, Salman M. Tajuddin, Renée de Mutsert, David J. Porteous, Susan Redline, Sarah E. Harris, Tamara B. Harris, Raha Pazoki, Mickaël Canouil, Robert A. Scott, Jingzhong Ding, Mary F. Feitosa, Jost B. Jonas, José Eduardo Krieger, John M. Starr, Karin Leander, Jennifer A. Smith, Paul W. Franks, Charles B. Eaton, Sharon L.R. Kardia, E. Shyong Tai, Jill M. Norris, Annette Peters, Chiamaka Vivian Nwuba, Jianjun Liu, Stella Aslibekyan, Nora Franceschini, Kurt Lohman, Myriam Fornage, Dina Vojinovic, Erin B. Ware, Xiaoyin Li, Najaf Amin, Johanna Kuusisto, M. Yldau van der Ende, Cora E. Lewis, Lynne E. Wagenknecht, Jennifer G. Robinson, Franco Giulianini, Ulf de Faire, Yechiel Friedlander, Nicholas J. Wareham, Meian He, George J. Papanicolau, Nancy L. Pedersen, Bernardo L. Horta, Karen L. Mohlke, Kelley Pettee Gabriel, Minjung Kho, Michele K. Evans, Ozren Polasek, Markku Laakso, Tuomas O. Kilpeläinen, Ching-Ti Liu, Michael Boehnke, Jin-Fang Chai, Ioanna Ntalla, Cornelia M. van Duijn, L. Adrienne Cupples, Yuri Milaneschi, Stephen Sidney, Alan B. Zonderman, Leo-Pekka Lyytikäinen, Mohsen Ghanbari, Harold Snieder, Donald W. Bowden, Aldi T. Kraja, Alaitz Poveda, Terho Lehtimäki, Paul S. de Vries, Dongfeng Gu, Sotoodehnia Nona, Thomas W. Winkler, Muhammad Riaz, Ian J. Deary, Fumihiko Takeuchi, Pim van der Harst, Alisa K. Manning, Michael A. Province, Andrea R. V. R. Horimoto, David R. Weir, Wei Zheng, Alanna C. Morrison, Marzyeh Amini, Jian-Min Yuan, W. James Gauderman, Paul M. Ridker, Melanie Waldenberger, Chuan Gao, Xiao-Ou Shu, Patricia B. Munroe, Patricia A. Peyser, Jessica D. Faul, Xu Chen, Brian E. Cade, Patrik K. E. Magnusson, Tamar Sofer, Home Office, Medical Research Council (MRC), National Institute for Health Research, Imperial College Healthcare NHS Trust- BRC Funding, UK DRI Ltd, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, APH - Mental Health, APH - Digital Health, IT University of Copenhagen, Icahn School of Medicine at Mount Sinai [New York] (MSSM), National Institutes of Health [Bethesda] (NIH), Leiden University Medical Center (LUMC), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), University of Regensburg, Brigham and Women's Hospital [Boston], Harvard Medical School [Boston] (HMS), Massachusetts General Hospital [Boston], Queen Mary University of London (QMUL), Département de Biologie Computationnelle - Department of Computational Biology, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), The University of Texas Health Science Center at Houston (UTHealth), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP), University of Washington [Seattle], The present work was largely supported by a grant from the US National Heart, Lung,and Blood Institute (NHLBI) of the National Institutes of Health (R01HL118305)., Kilpeläinen, Tuomas O., Bentley, Amy R., Noordam, Raymond, Sung, Yun Ju, Schwander, Karen, Winkler, Thomas W., Jakupović, Hermina, Chasman, Daniel I., Manning, Alisa, Ntalla, Ioanna, Aschard, Hugue, Brown, Michael R., de las Fuentes, Lisa, Franceschini, Nora, Guo, Xiuqing, Vojinovic, Dina, Aslibekyan, Stella, Feitosa, Mary F., Kho, Minjung, Musani, Solomon K., Richard, Melissa, Wang, Heming, Wang, Zhe, Bartz, Traci M., Bielak, Lawrence F., Campbell, Archie, Dorajoo, Rajkumar, Fisher, Virginia, Hartwig, Fernando P., Horimoto, Andrea R. V. R., Li, Changwei, Lohman, Kurt K., Marten, Jonathan, Sim, Xueling, Smith, Albert V., Tajuddin, Salman M., Alver, Mari, Amini, Marzyeh, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Evangelou, Evangelo, Gao, Chuan, Graff, Mariaelisa, Harris, Sarah E., He, Meian, Hsu, Fang-Chi, Jackson, Anne U., Zhao, Jing Hua, Kraja, Aldi T., Kühnel, Brigitte, Laguzzi, Federica, Lyytikäinen, Leo-Pekka, Nolte, Ilja M., Rauramaa, Rainer, Riaz, Muhammad, Robino, Antonietta, Rueedi, Rico, Stringham, Heather M., Takeuchi, Fumihiko, van der Most, Peter J., Varga, Tibor V., Verweij, Niek, Ware, Erin B., Wen, Wanqing, Li, Xiaoyin, Yanek, Lisa R., Amin, Najaf, Arnett, Donna K., Boerwinkle, Eric, Brumat, Marco, Cade, Brian, Canouil, Mickaël, Chen, Yii-Der Ida, Concas, Maria Pina, Connell, John, de Mutsert, Renée, de Silva, H. Janaka, de Vries, Paul S., Demirkan, Ayşe, Ding, Jingzhong, Eaton, Charles B., Faul, Jessica D., Friedlander, Yechiel, Gabriel, Kelley P., Ghanbari, Mohsen, Giulianini, Franco, Gu, Chi Charle, Gu, Dongfeng, Harris, Tamara B., He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hunt, Steven C., Ikram, M. Arfan, Jonas, Jost B., Koh, Woon-Puay, Komulainen, Pirjo, Krieger, Jose E., Kritchevsky, Stephen B., Kutalik, Zoltán, Kuusisto, Johanna, Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Leander, Karin, Lemaitre, Rozenn N., Lewis, Cora E., Liang, Jingjing, Alizadeh, Behrooz Z., Boezen, H. Marike, Franke, Lude, Navis, Gerjan, Rots, Marianne, Swertz, Morri, Wolffenbuttel, Bruce H. R., Wijmenga, Cisca, Liu, Jianjun, Mägi, Reedik, Manichaikul, Ani, Meitinger, Thoma, Metspalu, Andre, Milaneschi, Yuri, Mohlke, Karen L., Mosley, Thomas H., Murray, Alison D., Nalls, Mike A., Nang, Ei-Ei Khaing, Nelson, Christopher P., Nona, Sotoodehnia, Norris, Jill M., Nwuba, Chiamaka Vivian, O’Connell, Jeff, Palmer, Nicholette D., Papanicolau, George J., Pazoki, Raha, Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Porteous, David J., Poveda, Alaitz, Raitakari, Olli T., Rich, Stephen S., Risch, Neil, Robinson, Jennifer G., Rose, Lynda M., Rudan, Igor, Schreiner, Pamela J., Scott, Robert A., Sidney, Stephen S., Sims, Mario, Smith, Jennifer A., Snieder, Harold, Sofer, Tamar, Starr, John M., Sternfeld, Barbara, Strauch, Konstantin, Tang, Hua, Taylor, Kent D., Tsai, Michael Y., Tuomilehto, Jaakko, Uitterlinden, André G., van der Ende, M. Yldau, van Heemst, Diana, Voortman, Trudy, Waldenberger, Melanie, Wennberg, Patrik, Wilson, Gregory, Xiang, Yong-Bing, Yao, Jie, Yu, Caizheng, Yuan, Jian-Min, Zhao, Wei, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., de Faire, Ulf, Deary, Ian J., Elliott, Paul, Esko, Tõnu, Freedman, Barry I., Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Kato, Norihiro, Laakso, Markku, Lakka, Timo A., Lehtimäki, Terho, Magnusson, Patrik K. E., Oldehinkel, Albertine J., Penninx, Brenda W. J. H., Samani, Nilesh J., Shu, Xiao-Ou, van der Harst, Pim, Van Vliet-Ostaptchouk, Jana V., Vollenweider, Peter, Wagenknecht, Lynne E., Wang, Ya X., Wareham, Nicholas J., Weir, David R., Wu, Tangchun, Zheng, Wei, Zhu, Xiaofeng, Evans, Michele K., Franks, Paul W., Gudnason, Vilmundur, Hayward, Caroline, Horta, Bernardo L., Kelly, Tanika N., Liu, Yongmei, North, Kari E., Pereira, Alexandre C., Ridker, Paul M., Tai, E. Shyong, van Dam, Rob M., Fox, Ervin R., Kardia, Sharon L. R., Liu, Ching-Ti, Mook-Kanamori, Dennis O., Province, Michael A., Redline, Susan, van Duijn, Cornelia M., Rotter, Jerome I., Kooperberg, Charles B., Gauderman, W. Jame, Psaty, Bruce M., Rice, Kenneth, Munroe, Patricia B., Fornage, Myriam, Cupples, L. Adrienne, Rotimi, Charles N., Morrison, Alanna C., Rao, Dabeeru C., Loos, Ruth J. F., Bentley, Amy R [0000-0002-0827-9101], Jakupović, Hermina [0000-0001-9667-9406], Manning, Alisa [0000-0003-0247-902X], Aschard, Hugues [0000-0003-0907-2548], de Las Fuentes, Lisa [0000-0002-4689-325X], Richard, Melissa [0000-0003-0129-9860], Liu, Ching-Ti [0000-0002-0703-0742], Rice, Kenneth [0000-0002-3071-7278], Munroe, Patricia B [0000-0002-4176-2947], Loos, Ruth JF [0000-0002-8532-5087], Apollo - University of Cambridge Repository, Epidemiology, Radiology & Nuclear Medicine, Erasmus MC other, Internal Medicine, Læknadeild (HÍ), Faculty of Medicine (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland, IT University of Copenhagen (ITU), Universiteit Leiden, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Groningen Research Institute for Asthma and COPD (GRIAC), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Value, Affordability and Sustainability (VALUE), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Restoring Organ Function by Means of Regenerative Medicine (REGENERATE), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Cardiovascular Centre (CVC), Center for Liver, Digestive and Metabolic Diseases (CLDM), Stem Cell Aging Leukemia and Lymphoma (SALL), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Lifelines Cohort Study, Alizadeh, B.Z., Boezen, H.M., Franke, L., Navis, G., Rots, M., Swertz, M., Wolffenbuttel, BHR, and Wijmenga, C.
Subjects: Genetics and Molecular Biology (all), Male, Genome-wide association study, 02 engineering and technology, Biochemistry, MESH: Genotype, MESH: Nerve Tissue Proteins, lcsh:Science, MESH: Lipid Metabolism, Aged, 80 and over, [STAT.AP]Statistics [stat]/Applications [stat.AP], MESH: Middle Aged, MESH: Asian Continental Ancestry Group, Kólesteról, Hispanic or Latino, MESH: Transcription Factors, MESH: European Continental Ancestry Group, Lipids, ddc, 3. Good health, REVEAL, Cholesterol, MESH: Young Adult, Science & Technology - Other Topics, MESH: Membrane Proteins, MESH: Cholesterol, HDL, Hispanic Americans, 0210 nano-technology, Erfðarannsóknir, MESH: Cholesterol, LDL, MESH: Triglycerides, Genotype, Genetic Loci, Lipid Metabolism, Science, European Continental Ancestry Group, LIM-Homeodomain Proteins, Locus (genetics), EXERCISE, Adolescent, Adult, African Continental Ancestry Group/genetics, Aged, Asian Continental Ancestry Group/genetics, Brazil, Calcium-Binding Proteins/genetics, Cholesterol/blood, Cholesterol, HDL/blood, Cholesterol, HDL/genetics, Cholesterol, LDL/blood, Cholesterol, LDL/genetics, European Continental Ancestry Group/genetics, Exercise, Female, Genetic Loci/genetics, Genome-Wide Association Study, Hispanic Americans/genetics, Humans, LIM-Homeodomain Proteins/genetics, Lipid Metabolism/genetics, Lipids/blood, Lipids/genetics, Membrane Proteins/genetics, Microtubule-Associated Proteins/genetics, Middle Aged, Muscle Proteins/genetics, Nerve Tissue Proteins/genetics, Transcription Factors/genetics, Triglycerides/blood, Triglycerides/genetics, Young Adult, General Biochemistry, Genetics and Molecular Biology, Article, White People, CARBOXYLASE, 03 medical and health sciences, Physics and Astronomy (all), MESH: Muscle Proteins, Asian People, Lifelines Cohort Study, SNP, METAANALYSIS, Ancestry, MESH: Adolescent, Biochemistry, Genetics and Molecular Biology (all), MESH: Humans, Science & Technology, Calcium-Binding Proteins, MESH: Adult, MESH: Microtubule-Associated Proteins, 030104 developmental biology, chemistry, MESH: Genome-Wide Association Study, lcsh:Q, MESH: African Continental Ancestry Group, Chemistry (all), [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], MESH: Brazil, MESH: Female, Transcription Factors, 0301 basic medicine, General Physics and Astronomy, Blood lipids, Muscle Proteins, MESH: Calcium-Binding Proteins, chemistry.chemical_compound, MESH: Aged, 80 and over, MESH: Cholesterol, WIDE ASSOCIATION, African Continental Ancestry Group, Genetics, MESH: Aged, Multidisciplinary, Public Health, Global Health, Social Medicine and Epidemiology, 021001 nanoscience & nanotechnology, Multidisciplinary Sciences, lipids (amino acids, peptides, and proteins), Medical Genetics, [STAT.ME]Statistics [stat]/Methodology [stat.ME], Microtubule-Associated Proteins, Asian Continental Ancestry Group, Black People, Nerve Tissue Proteins, Biology, MESH: Genetic Loci, MD Multidisciplinary, Triglycerides, Medicinsk genetik, MESH: LIM-Homeodomain Proteins, Triglyceride, MESH: Hispanic Americans, Cholesterol, HDL, Genome-wide analyses, Membrane Proteins, Lipid metabolism, General Chemistry, Cholesterol, LDL, Arfgengi, MESH: Lipids, MESH: Male, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, INDIVIDUALS, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, MESH: Exercise, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract: Publisher's version (útgefin grein), Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels., The present work was largely supported by a grant from the US National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (R01HL118305). The full list of acknowledgments appears in the Supplementary Notes 3 and 4.
Published: 2018

30. Local ancestry at APOE modifies Alzheimer's disease risk in Caribbean Hispanics

Author: Andrea R. V. R. Horimoto, Shubhabrata Mukherjee, Timothy A. Thornton, Elizabeth E. Blue, and Ellen M. Wijsman
Subjects: 0301 basic medicine, Apolipoprotein E, Male, Genotype, Epidemiology, Black People, Disease, European descent, White People, Article, Odds, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Apolipoproteins E, Developmental Neuroscience, Alzheimer Disease, Genetic variation, Ethnicity, Medicine, Humans, Age of Onset, Aged, business.industry, Health Policy, Hispanic or Latino, Middle Aged, Psychiatry and Mental health, 030104 developmental biology, Caribbean Region, Disease risk, lipids (amino acids, peptides, and proteins), Female, Neurology (clinical), Geriatrics and Gerontology, business, 030217 neurology & neurosurgery, Demography
Abstract: Introduction Although the relationship between APOE and Alzheimer's disease (AD) is well established in populations of European descent, the effects of APOE and ancestry on AD risk in diverse populations is not well understood. Methods Logistic mixed model regression and survival analyses were performed in a sample of 3067 Caribbean Hispanics and 3028 individuals of European descent to assess the effects of APOE genotype, local ancestry, and genome-wide ancestry on AD risk and age at onset. Results Among the Caribbean Hispanics, individuals with African-derived ancestry at APOE had 39% lower odds of AD than individuals with European-derived APOE, after adjusting for APOE genotype, age, and genome-wide ancestry. While APOE E2 and E4 effects on AD risk and age at onset were significant in the Caribbean Hispanics, they were substantially attenuated compared with those in European ancestry individuals. Discussion These results suggest that additional genetic variation in the APOE region influences AD risk beyond APOE E2/E3/E4.
Published: 2018

31. Cohort Profile: The Cohorts Consortium of Latin America and the Caribbean (CC-LAC)

Author: Leila Beltrami Moreira, Betty S Manrique-Espinoza, Elard Koch, Dalia Stern, Catterina Ferreccio, Claudia Bambs, Adrian Cortes-Valencia, Ione Jayce Ceola Schneider, Marselle B Amadio, José Geraldo Mill, José Boggia, Gilbert Brenes-Camacho, Lariane M Ono, Alvaro Cc Maciel, Walter G Espeche, Poli Mara Spritzer, Fernando Luiz Herkenhoff, J. Jaime Miranda, Adolfo Rubinstein, Horacio A Carbajal, Cecilia Baccino, Andrea R. V. R. Horimoto, Anselm Hennis, Gonzalo Grazioli, Mariachiara Di Cesare, Katia Vergetti Bloch, Ricardo Oliveira Guerra, Gloria L. Beckles, João Luiz Bastos, Álvaro Ruiz-Morales, Alexandre C. Pereira, Ramon A Sanchez, Fiorella Tartaglione, Antonio Bernabe-Ortiz, Roberto de Sa Cunha, Luis Rosero-Bixby, Vilma Irazola, Rodrigo M. Carrillo-Larco, Martin R Salazar, Thiago L N Silva, Pollyanna Kássia de Oliveira Borges, Ian Hambleton, Juan E. Blümel, Flávio Danni Fuchs, Aaron Salinas-Rodriguez, Ramón Álvarez-Vaz, Eleonora d'Orsi, David Alejandro González-Chica, Paulo A. Lotufo, Sérgio Viana Peixoto, Sandra Cortés, Goodarz Danaei, Rosalba Rojas-Martínez, Suely Godoy Agostinho Gimeno, Karen Glazer Peres, Jackie A. Cooper, Maria Fernanda Lima-Costa, Larissa Pruner Marques, Marco Aurélio Peres, Nohora I Rodriguez, William H. Dow, Edward W. Gregg, Laura Gutierrez, Clicerio González-Villalpando, Liam Smeeth, Jorge Tartaglione, Miguel Bravo, Oscar Muñoz, Maria S. Castillo Rascon, Karen Oppermann, María-Elena González-Villalpando, Blanca H. Ceballos, Susana Cararo Confortin, Ruy Lopez-Ridaura, Majid Ezzati, Andrea Huidobro, Carlos A. Aguilar-Salinas, Verônica Colpani, Sandra C. Fuchs, Nelson A S Silva, Donaji Gomez-Velasco, Pablo Perel, Martin Lajous, and Carla de Oliveira Bernardo
Subjects: 0301 basic medicine, medicine.medical_specialty, Framingham Risk Score, Latin Americans, Epidemiology, business.industry, General Medicine, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Health care, Cohort, Global health, Medicine, AcademicSubjects/MED00860, 030212 general & internal medicine, business, Cohort Profiles, Disease burden, Demography, Cohort study
Abstract: Why was the cohort set up? Latin America and the Caribbean (LAC) are characterized by much diversity in terms of socio-economic status, ecology, environment, access to health care,1,2 as well as the frequency of risk factors for and prevalence or incidence of non-communicable diseases;3–7 importantly, these differences are observed both between and within countries in LAC.8,9 LAC countries share a large burden of non-communicable (e.g. diabetes and hypertension) and cardiovascular (e.g. ischaemic heart disease) diseases, with these conditions standing as the leading causes of morbidity, disability and mortality in most of LAC.10–12 These epidemiological estimates—e.g. morbidity—cannot inform about risk factors or risk prediction, which are relevant to identify prevention avenues. Cohort studies, on the other hand, could provide this evidence. Pooled analysis, using data from multiple cohort studies, have additional strengths such as increased statistical power and decreased statistical uncertainty.13 LAC cohort studies have been under-represented,14 or not included at all,15–17 in international efforts aimed at pooling data from multiple cohort studies. We therefore set out to pool data from LAC cohorts to address research questions that individual cohort studies would not be able to answer. Drawing from previous successful regional enterprises (e.g. Asia Pacific Cohort Studies Collaboration),18,19 we established the Cohorts Consortium of Latin America and the Caribbean (CC-LAC). The main aim of the CC-LAC is to start a collaborative cohort data pooling in LAC to examine the association between cardio-metabolic risk factors (e.g. blood pressure, glucose and lipids) and non-fatal and fatal cardiovascular outcomes (e.g. stroke or myocardial infarction). In so doing, we aim to provide regional risk estimates to inform disease burden metrics, as well as other ambitious projects including a cardiovascular risk score to strengthen cardiovascular prevention in LAC. Initial funding has been provided by a fellowship from the Wellcome Trust Centre for Global Health Research at Imperial College London (Strategic Award, Wellcome Trust–Imperial College Centre for Global Health Research, 100693/Z/12/Z). Additional funding is being provided by an International Training Fellowship from the Wellcome Trust (214185/Z/18/Z). At the time of writing, the daily operations and pooled database are hosted at Imperial College London, though a mid-term goal is to transfer this expertise and operations to LAC. The collaboration relies fundamentally on a strong regional network of health researchers and practitioners
Published: 2020

32. Genetic epidemiology of insomnia in the Baependi heart cohort study

Author: Felipe Beijamini, Luz Marina Gomez Gomez, Kristen L. Knutson, André B. Negrão, Alexandre C. Pereira, Annette Sterr, M. von Schantz, Tâmara P. Taporoski, Sabrina S. Ahmed, Andrea R. V. R. Horimoto, and Francieli S. Ruiz
Subjects: Pediatrics, medicine.medical_specialty, Genetic epidemiology, business.industry, Insomnia, Medicine, General Medicine, medicine.symptom, business, Cohort study
Published: 2019

33. Prevalence of Peripheral Artery Disease and Associated Risk Factors in a Brazilian Rural Population: The Baependi Heart Study

Author: Rafael de Oliveira Alvim, Alexandre C. Pereira, José Eduardo Krieger, Andrea R. V. R. Horimoto, Fernando Augusto Lavezzo Dias, Camila Maciel de Oliveira, and Anderson Zampier Ulbrich
Subjects: Rural Population, Fatores de Risco, medicine.medical_specialty, Tabagismo, Peripheral Arterial Disease / prevalence, Arterial disease, business.industry, Disease, Tobacco Use Disorder, 030204 cardiovascular system & hematology, Ankle-Brachial Index, Cardiovascular death, 03 medical and health sciences, 0302 clinical medicine, Age groups, Doença Arterial Periférica / prevalência, Risk Factors, Internal medicine, medicine, População Rural, 030212 general & internal medicine, Risk factor, business, Índice Tornozelo-Braço
Abstract: Background: The identification of peripheral artery disease (PAD) can help prevent further progression of the disease and additional complications, considering that this condition is a risk factor for all-cause mortality and cardiovascular death. Objective: To assess the prevalence of PAD in the Baependi Heart Study and investigate associated risk factors in different age groups. Methods: A total of 1,627 individuals (of both genders and aged 18 - 102 years) residing in the municipality of Baependi (Minas Gerais, Brazil) were selected for this study. Anthropometric and biochemical parameters were evaluated by standard techniques. Physical activity level was determined by the International Physical Activity Questionnaire - Short Form (IPAQ-SF). The screening of PAD was performed by determination of the ankle-brachial index (ABI). The level of statistical significance was set at 5%. Results: In the overall sample, the prevalence of PAD was 1.05%, and reached 5.2% after the age of 70 years. The frequency and intensity of smoking were higher in individuals with PAD. A prior history of myocardial infarction and a higher prevalence of hypertension, diabetes, obesity, and sedentary lifestyle were also associated with PAD. In addition, PAD was more frequent in blacks than whites. In multivariable analysis, age, diabetes, smoking, and physical inactivity remained independently associated with PAD. Conclusion: The prevalence of PAD was low and increased clearly with age in our sample from a Brazilian rural population. Furthermore, the main risk factors for PAD in the investigated sample were smoking, sedentary lifestyle, diabetes mellitus, and age. (Int J Cardiovasc Sci. 2018; [online].ahead print, PP.0-0) Resumo Fundamentos: A identificação da doença arterial periférica (DAP) pode atenuar a progressão e suas complicações adicionais, uma vez que a DAP é um fator de risco para mortalidade geral e cardiovascular. Objetivo: Avaliar a prevalência de DAP na população do Estudo Corações de Baependi e investigar fatores de risco associados em diferentes grupos etários. Métodos: Foram selecionados 1.627 indivíduos (ambos os sexos e idade entre 18 e 102 anos) residentes no município de Baependi (Minas Gerais, Brasil). Os parâmetros antropométricos e bioquímicos foram avaliados por meio de protocolos padrões. O nível de atividade física foi determinado pelo Questionário Internacional de Atividade Física - Versão Curta (IPAQ-SF). A triagem da DAP foi realizada pelo índice tornozelo-braço (ITB). O nível de significância estatística adotado nas análises foi de 5%. Resultados: Na população total, a prevalência de DAP foi de 1,05% e atingiu 5,2% após os 70 anos de idade. A frequência e intensidade do tabagismo foram maiores nos indivíduos com DAP. Uma história prévia de infarto do miocárdio e maior prevalência de hipertensão, diabetes, obesidade e sedentarismo também estiveram associados à DAP. Além disso, a DAP foi mais frequente em negros que em brancos. Após análise multivariada, a idade, diabetes, tabagismo e inatividade física permaneceram independentemente associados à DAP. Conclusão: A prevalência de DAP foi baixa e claramente aumentou com a idade em nossa amostra de uma população rural brasileira. Além disso, os principais fatores de risco para DAP foram tabagismo, sedentarismo, diabetes e idade. (Int J Cardiovasc Sci. 2018; [online].ahead print, PP.0-0)
Published: 2018

34. Analysis of Pedigree Data in Populations with Multiple Ancestries: Strategies for Dealing with Admixture in Caribbean Hispanic Families from the ADSP

Author: Lisa M. Brown, Timothy A. Thornton, Bowen Wang, Sandra Barral, Harkirat Sohi, Alejandro Q. Nato, Giuseppe Tosto, Andrea R. V. R. Horimoto, Rafael A. Nafikov, Elizabeth Blue, Richard Mayeux, Ellen M. Wijsman, and Badri N. Vardarajan
Subjects: 0301 basic medicine, Male, Epidemiology, Genetic Linkage, Population structure, Pedigree chart, Sample (statistics), Biology, Genome, Article, 03 medical and health sciences, Gene Frequency, Genetic linkage, Alzheimer Disease, Ethnicity, Humans, Family, Allele frequency, Genetics (clinical), Phylogeny, Principal Component Analysis, Models, Genetic, Gene Pool, Hispanic or Latino, Sequence Analysis, DNA, Pedigree, 030104 developmental biology, Genetics, Population, Caribbean Region, Evolutionary biology, Female, Lod Score
Abstract: Multipoint linkage analysis is an important approach for localizing disease-associated loci in pedigrees. Linkage analysis, however, is sensitive to misspecification of marker allele frequencies. Pedigrees from recently admixed populations are particularly susceptible to this problem because of the challenge of accurately accounting for population structure. Therefore, increasing emphasis on use of multiethnic samples in genetic studies requires reevaluation of best practices, given data currently available. Typical strategies have been to compute allele frequencies from the sample, or to use marker allele frequencies determined by admixture proportions averaged over the entire sample. However, admixture proportions vary among pedigrees and throughout the genome in a family-specific manner. Here, we evaluate several approaches to model admixture in linkage analysis, providing different levels of detail about ancestral origin. To perform our evaluations, for specification of marker allele frequencies, we used data on 67 Caribbean Hispanic admixed families from the Alzheimer's Disease Sequencing Project. Our results show that choice of admixture model has an effect on the linkage analysis results. Variant-specific admixture proportions, computed for individual families, provide the most detailed regional admixture estimates, and, as such, are the most appropriate allele frequencies for linkage analysis. This likely decreases the number of false-positive results, and is straightforward to implement.
Published: 2018

35. A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure

Author: Patricia A. Peyser, Jessica D. Faul, Sing Hui Lim, Xu Chen, Brian E. Cade, Patrik K. E. Magnusson, John C. Chambers, Tamar Sofer, Marzyeh Amini, Benjamin Lehne, W. James Gauderman, Wei Zhao, Andres Metspalu, R. Graham Barr, Albertine J. Oldehinkel, Xueling Sim, Norihiro Kato, Daniel I. Chasman, Jasmin Divers, Fernando Pires Hartwig, Jing Hua Zhao, Yu Caizheng, Roby Joehanes, Nora Franceschini, Nita G. Forouhi, Charumathi Sabanayagam, Paul M. Ridker, Yun J. Sung, Mary F. Feitosa, Barbara V. Howard, Vilmundur Gudnason, Jost B. Jonas, Hua Tang, Yukihide Momozawa, Michael R. Brown, Tibor V. Varga, Franco Giulianini, Francis S. Collins, Alexander P. Reiner, Ulrich Broeckel, Tuomo Rankinen, Preeti Gupta, Tin Louie, Eric Boerwinkle, Saskia P. Hagenaars, Mark J. Caulfield, Albert Hofman, Aravinda Chakravarti, Paul W. Franks, Nicole Schupf, E. Shyong Tai, Carl D. Langefeld, Carsten Oliver Schmidt, Lawrence F. Bielak, Treva Rice, Anne B. Newman, Ioanna Ntalla, Kae-Woei Liang, Nilesh J. Samani, Alena Stančáková, Thomas H. Mosley, Dan E. Arking, Kenneth Rice, Bruce M. Psaty, Jirong Long, Yechiel Friedlander, Jianjun Liu, Donna K. Arnett, Ya X. Wang, Xiuqing Guo, Anne E. Justice, Pamela J. Schreiner, Renée de Mutsert, Lisa de las Fuentes, Marcus Dörr, Amy R. Bentley, Susan Redline, Cornelia M. van Duijn, Melissa A. Richard, Sarah E. Harris, Pirjo Komulainen, Nicholette D. Palmer, Alexandre C. Pereira, Michele K. Evans, Jie Yao, Adesola Ogunniyi, Wen Bin Wei, Anuradhani Kasturiratne, Yoichiro Kamatani, Charles Kooperberg, Helen R. Warren, Shiow Lin, Ozren Polasek, Makoto Hirata, Anubha Mahajan, Yingchang Lu, Jonathan Marten, Claudia P. Cabrera, Chuan Gao, Oscar H. Franco, Yongmei Liu, Mathilde Boissel, Olli T. Raitakari, Xiao-Ou Shu, Yii-Der Ida Chen, Y Liu, Claudia Langenberg, C. Charles Gu, Cathy C. Laurie, Tamuno Alfred, L. Adrienne Cupples, Yajuan Wang, Colin A. McKenzie, Mika Kähönen, Yize Li, Xiaofeng Zhu, Nana Matoba, James Scott, Marguerite R. Irvin, Markku Laakso, Frida Renström, Woon-Puay Koh, Dabeeru C. Rao, Yucheng Jia, Paul Elliott, Tangchun Wu, Caroline Hayward, Tamara B. Harris, Alison D. Murray, Karin Leander, Reedik Mägi, Keng-Hung Lin, Harold Snieder, Laura J. Bierut, Christine Williams, Solomon K. Musani, Michael A. Province, Charles B. Eaton, Sharon L.R. Kardia, Mario Sims, Steven C. Hunt, Stephen B. Kritchevsky, Weihua Zhang, David R. Weir, Andrea R. V. R. Horimoto, Saima Afaq, Hugues Aschard, Ilaria Gandin, Michiaki Kubo, Jaspal S. Kooner, Peter S. Braund, Jeffrey R. O'Connell, Kent D. Taylor, Annette Peters, Wei Zheng, Rainer Rettig, Nicola D. Kerrison, Donald W. Bowden, Ruth J. F. Loos, Tanika N. Kelly, Dennis O. Mook-Kanamori, Terrence Forrester, Igor Rudan, Brigitte Kühnel, Christopher P. Nelson, Ching-Yu Cheng, Alanna C. Morrison, Tuomas O. Kilpeläinen, Jian-Min Yuan, Bruna Gigante, Lisa R. Yanek, Ching-Ti Liu, Ananda R. Wickremasinghe, Michael Boehnke, Tin Aung, Jin-Fang Chai, Kaare Christensen, Wen-Jane Lee, Stéphanie Debette, Jennifer A. Brody, Wayne Huey-Herng Sheu, John M. C. Connell, Ganesh Chauhan, Jian'an Luan, Melanie Waldenberger, Erin B. Ware, Paolo Gasparini, Chew-Kiat Heng, Lili Milani, Alisa K. Manning, José Eduardo Krieger, Kiang Liu, Mickaël Canouil, Robert A. Scott, Yik Ying Teo, Gregory P. Wilson, Stella Aslibekyan, Andrew P. Morris, Thomas Meitinger, Jennifer A. Smith, Yi-Jen Hung, Myriam Fornage, Dina Vojinovic, William R. Scott, Virginia Fisher, Peter S. Sever, André G. Uitterlinden, Najaf Amin, Lenore J. Launer, Hugh Watkins, Johanna Kuusisto, Rajkumar Dorajoo, Georg Ehret, Heming Wang, Sandosh Padmanabhan, Jingmin Liu, Colleen M. Sitlani, Anuj Goel, Bamidele O. Tayo, Daniel Levy, Barry I. Freedman, Marie Loh, Yanhua Zhou, Charles N. Rotimi, Qing Duan, Aldi T. Kraja, He Meian, Archie Campbell, Kari E. North, Tien Yin Wong, Salman M. Tajuddin, Traci M. Bartz, Mike A. Nalls, Misa Graff, Dongfeng Gu, Sudha Seshadri, Tõnu Esko, Antonietta Robino, Anne U. Jackson, H. Janaka de Silva, Peter J. van der Most, Fang-Chi Hsu, Chiea Chuen Khor, Changwei Li, Sami Heikkinen, Maris Alver, Karen Schwander, Wanqing Wen, Rainer Rauramaa, Lynne E. Wagenknecht, Ubaydah Nasri, Peter J. Munson, He Gao, Evangelos Evangelou, Philippe Froguel, Ervin R. Fox, Christian Gieger, Kurt Lohman, James S. Pankow, Nicholas J. Wareham, Lynda M. Rose, Massimiliano Cocca, Rob M. van Dam, John M. Starr, Martin Farrall, Stefan Weiss, Konstantin Strauch, Albert V. Smith, Jill M. Norris, Raymond Noordam, Cora E. Lewis, Claude Bouchard, Ulf de Faire, Walter Palmas, Diane M. Becker, Kevin Sandow, Tomohiro Katsuya, Jiang He, Nancy L. Pedersen, Bernardo L. Horta, Joel D. Kaufman, Terho Lehtimäki, Heikki A. Koistinen, Thomas W. Winkler, Ian J. Deary, Richard S. Cooper, Fumihiko Takeuchi, Jerome I. Rotter, Lihua Wang, Yih Chung Tham, Babatunde L. Salako, Mary K. Wojczynski, Pim van der Harst, Jennifer G. Robinson, Erwin P. Bottinger, Alan B. Zonderman, Patricia B. Munroe, Ehret, Georg Benedikt, Harvard School of Public Health, Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP), 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), The various Gene-Lifestyle Interaction projects, including this one, are largely supported by a grant from the U.S. National Heart, Lung, and Blood Institute (NHLBI), the National Institutes of Health, R01HL118305. A Career Development Award (K25HL121091), also from the NHLBI, enabled Y.J.S. to lead this project. Full set of study-specific funding sources and acknowledgments appear in the Supplemental Note., Sung, Yun J., Winkler, Thomas W., de las Fuentes, Lisa, Bentley, Amy R., Brown, Michael R., Kraja, Aldi T., Schwander, Karen, Ntalla, Ioanna, Guo, Xiuqing, Franceschini, Nora, Lu, Yingchang, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Marten, Jonathan, Musani, Solomon K., Li, Changwei, Feitosa, Mary F., Kilpeläinen, Tuomas O., Richard, Melissa A., Noordam, Raymond, Aslibekyan, Stella, Aschard, Hugue, Bartz, Traci M., Dorajoo, Rajkumar, Liu, Yongmei, Manning, Alisa K., Rankinen, Tuomo, Smith, Albert Vernon, Tajuddin, Salman M., Tayo, Bamidele O., Warren, Helen R., Zhao, Wei, Zhou, Yanhua, Matoba, Nana, Sofer, Tamar, Alver, Mari, Amini, Marzyeh, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gandin, Ilaria, Gao, Chuan, Giulianini, Franco, Goel, Anuj, Harris, Sarah E., Hartwig, Fernando Pire, Horimoto, Andrea R. V. R., Hsu, Fang-Chi, Jackson, Anne U., Kähönen, Mika, Kasturiratne, Anuradhani, Kühnel, Brigitte, Leander, Karin, Lee, Wen-Jane, Lin, Keng-Hung, ’an Luan, Jian, Mckenzie, Colin A., Meian, He, Nelson, Christopher P., Rauramaa, Rainer, Schupf, Nicole, Scott, Robert A., Sheu, Wayne H. H., Stančáková, Alena, Takeuchi, Fumihiko, van der Most, Peter J., Varga, Tibor V., Wang, Heming, Wang, Yajuan, Ware, Erin B., Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R., Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Alfred, Tamuno, Amin, Najaf, Arking, Dan, Aung, Tin, Barr, R. Graham, Bielak, Lawrence F., Boerwinkle, Eric, Bottinger, Erwin P., Braund, Peter S., Brody, Jennifer A., Broeckel, Ulrich, Cabrera, Claudia P., Cade, Brian, Caizheng, Yu, Campbell, Archie, Canouil, Mickaël, Chakravarti, Aravinda, Chauhan, Ganesh, Christensen, Kaare, Cocca, Massimiliano, Collins, Francis S., Connell, John M., de Mutsert, Renée, de Silva, H. Janaka, Debette, Stephanie, Dörr, Marcu, Duan, Qing, Eaton, Charles B., Ehret, Georg, Evangelou, Evangelo, Faul, Jessica D., Fisher, Virginia A., Forouhi, Nita G., Franco, Oscar H., Friedlander, Yechiel, Gao, He, Gigante, Bruna, Graff, Misa, Gu, C. Charle, Gu, Dongfeng, Gupta, Preeti, Hagenaars, Saskia P., Harris, Tamara B., He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hirata, Makoto, Hofman, Albert, Howard, Barbara V., Hunt, Steven, Irvin, Marguerite R., Jia, Yucheng, Joehanes, Roby, Justice, Anne E., Katsuya, Tomohiro, Kaufman, Joel, Kerrison, Nicola D., Khor, Chiea Chuen, Koh, Woon-Puay, Koistinen, Heikki A., Komulainen, Pirjo, Kooperberg, Charle, Krieger, Jose E., Kubo, Michiaki, Kuusisto, Johanna, Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Lehne, Benjamin, Lewis, Cora E., Li, Yize, Lim, Sing Hui, Lin, Shiow, Liu, Ching-Ti, Liu, Jianjun, Liu, Jingmin, Liu, Kiang, Liu, Yeheng, Loh, Marie, Lohman, Kurt K., Long, Jirong, Louie, Tin, Mägi, Reedik, Mahajan, Anubha, Meitinger, Thoma, Metspalu, Andre, Milani, Lili, Momozawa, Yukihide, Morris, Andrew P., Mosley, Thomas H., Munson, Peter, Murray, Alison D., Nalls, Mike A., Nasri, Ubaydah, Norris, Jill M., North, Kari, Ogunniyi, Adesola, Padmanabhan, Sandosh, Palmas, Walter R., Palmer, Nicholette D., Pankow, James S., Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Raitakari, Olli T., Renström, Frida, Rice, Treva K., Ridker, Paul M., Robino, Antonietta, Robinson, Jennifer G., Rose, Lynda M., Rudan, Igor, Sabanayagam, Charumathi, Salako, Babatunde L., Sandow, Kevin, Schmidt, Carsten O., Schreiner, Pamela J., Scott, William R., Seshadri, Sudha, Sever, Peter, Sitlani, Colleen M., Smith, Jennifer A., Snieder, Harold, Starr, John M., Strauch, Konstantin, Tang, Hua, Taylor, Kent D., Teo, Yik Ying, Tham, Yih Chung, Uitterlinden, André G., Waldenberger, Melanie, Wang, Lihua, Wang, Ya X., Wei, Wen Bin, Williams, Christine, Wilson, Gregory, Wojczynski, Mary K., Yao, Jie, Yuan, Jian-Min, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., Chambers, John C., Chen, Yii-Der Ida, de Faire, Ulf, Deary, Ian J., Esko, Tõnu, Farrall, Martin, Forrester, Terrence, Franks, Paul W., Freedman, Barry I., Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Horta, Bernardo Lessa, Hung, Yi-Jen, Jonas, Jost B., Kato, Norihiro, Kooner, Jaspal S., Laakso, Markku, Lehtimäki, Terho, Liang, Kae-Woei, Magnusson, Patrik K. E., Newman, Anne B., Oldehinkel, Albertine J., Pereira, Alexandre C., Redline, Susan, Rettig, Rainer, Samani, Nilesh J., Scott, Jame, Shu, Xiao-Ou, van der Harst, Pim, Wagenknecht, Lynne E., Wareham, Nicholas J., Watkins, Hugh, Weir, David R., Wickremasinghe, Ananda R., Wu, Tangchun, Zheng, Wei, Kamatani, Yoichiro, Laurie, Cathy C., Bouchard, Claude, Cooper, Richard S., Evans, Michele K., Gudnason, Vilmundur, Kardia, Sharon L. R., Kritchevsky, Stephen B., Levy, Daniel, O'Connell, Jeff R., Psaty, Bruce M., van Dam, Rob M., Sims, Mario, Arnett, Donna K., Mook-Kanamori, Dennis O., Kelly, Tanika N., Fox, Ervin R., Hayward, Caroline, Fornage, Myriam, Rotimi, Charles N., Province, Michael A., van Duijn, Cornelia M., Tai, E. Shyong, Wong, Tien Yin, Loos, Ruth J. F., Reiner, Alex P., Rotter, Jerome I., Zhu, Xiaofeng, Bierut, Laura J., Gauderman, W. Jame, Caulfield, Mark J., Elliott, Paul, Rice, Kenneth, Munroe, Patricia B., Morrison, Alanna C., Cupples, L. Adrienne, Rao, Dabeeru C., Chasman, Daniel I., Marten, Jonathan [0000-0001-6916-2014], Zhao, Jing Hua [0000-0003-4930-3582], Forouhi, Nita [0000-0002-5041-248X], Langenberg, Claudia [0000-0002-5017-7344], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Life Course Epidemiology (LCE), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Cardiovascular Centre (CVC), Epidemiology, Internal Medicine, Gastroenterology & Hepatology, Clinicum, Department of Medicine, Endokrinologian yksikkö, HUS Internal Medicine and Rehabilitation, and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Male, multi-ancestry, Smoking/genetics, Genome-wide association study, Continental Population Groups/genetics, INTIMA-MEDIA THICKNESS, Cohort Studies, Diastole, Polymorphism (computer science), GWAS, TRANSTORNOS RELACIONADOS AO USO DE ÁLCOOL, GENE-ENVIRONMENT INTERACTION, Genetics (clinical), ddc:616, INSULIN-RESISTANCE, Multi-ancestry, Smoking, 1184 Genetics, developmental biology, physiology, blood pressure, GxE interaction, Diastole/genetics, 3. Good health, FALSE DISCOVERY RATE, Blood pressure, Medical genetics, CORONARY-ARTERY-DISEASE, Female, Single Nucleotide/genetics, Systole/genetics, BODY-MASS INDEX, ASSOCIATION ANALYSIS, COMMON VARIANTS, METAANALYSIS, DISEASE, OBESITY, JOINT, medicine.medical_specialty, lifestyle, SUSCEPTIBILITY LOCI, Blood Pressure/genetics, Systole, Quantitative Trait Loci, Single-nucleotide polymorphism, Accounting, Biology, Quantitative trait locus, Polymorphism, Single Nucleotide, GxE interactions, Article, smoking, 03 medical and health sciences, Genetic, medicine, Genetics, Journal Article, Humans, Polymorphism, Genetic association, ALCOHOL DEPENDENCE, business.industry, Racial Groups, Reproducibility of Results, Epistasis, Genetic, ta3121, Lifestyle, Genetic architecture, NICOTINE DEPENDENCE, 030104 developmental biology, Genetic Loci, Epistasis, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 3111 Biomedicine, business, Quantitative Trait Loci/genetics, Genome-Wide Association Study
Abstract: The authors declare no competing financial interests except for the following. B.M.P. serves on the DSMB of a clinical trial funded by the manufacturer (Zoll LifeCor) and on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson; O.H.F. received grants from Metagenics (on women’s health and epigenetics) and from Nestle (on child health); L.J.B. is listed as an inventor on Issued U.S. Patent 8,080,371,“Markers for Addiction” covering the use of certain SNPs in determining the diagnosis, prognosis, and treatment of addiction; P.S. has received research awards from Pfizer Inc., is a consultant for Mundipharma Co. (Cambridge, UK), is a patent holder with Biocompatibles UK Ltd. (Franham, Surrey, UK) (Title: Treatment of eye diseases using encapsulated cells encoding and secreting neuroprotective factor and/or anti-angiogenic factor; Patent number: 20120263794), and has a patent application with University of Heidelberg (Heidelberg, Germany) (Title: Agents for use in the therapeutic or prophylactic treatment of myopia or hyperopia; Europäische Patentanmeldung 15 000 771.4); P.W.F. has been a paid consultant for Eli Lilly and Sanofi Aventis and has received research support from several pharmaceutical companies as part of a European Union Innovative Medicines Initiative (IMI) project; M.A.N.’s participation is supported by a consulting contract between Data Tecnica Internation and the National Institute on Aging (NIH, Bethesda, MD, USA), and he also consults for Illumina, Inc., the Michael J. Fox Foundation, and University of California Healthcare among others; and M.J.C. is Chief Scientist for Genomics England, a UK government company.; International audience; Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed genome-wide association meta-analyses of systolic and diastolic BP incorporating gene-smoking interactions in 610,091 individuals. Stage 1 analysis examined approximately 18.8 million SNPs and small insertion/deletion variants in 129,913 individuals from four ancestries (European, African, Asian, and Hispanic) with follow-up analysis of promising variants in 480,178 additional individuals from five ancestries. We identified 15 loci that were genome-wide significant (p < 5 x 10(-8)) in stage 1 and formally replicated in stage 2. A combined stage 1 and 2 meta-analysis identified 66 additional genome-wide significant loci (13, 35, and 18 loci in European, African, and trans-ancestry, respectively). A total of 56 known BP loci were also identified by our results (p < 5 x 10(-8)). Of the newly identified loci, ten showed significant interaction with smoking status, but none of them were replicated in stage 2. Several loci were identified in African ancestry, highlighting the importance of genetic studies in diverse populations. The identified loci show strong evidence for regulatory features and support shared pathophysiology with cardiometabolic and addiction traits. They also highlight a role in BP regulation for biological candidates such as modulators of vascular structure and function (CDKN1B, BCAR1-CFDP1, PXDN, EEA1), ciliopathies (SDCCAG8, RPGRIP1L), telomere maintenance (TNKS, PINX1, AKTIP), and central dopaminergic signaling (MSRA, EBF2).
Published: 2018

36. Multi-ethnic genome-wide association study for atrial fibrillation

Author: Marcus E. Kleber, Raji P. Grewal, Yingchang Lu, Sanghamitra Mohanty, Harry J.G.M. Crijns, Han Sun, Ilkka Seppälä, Jonathan D. Smith, Albert Hofman, Yii-Der Ida Chen, Diane Fatkin, Patrik K. E. Magnusson, Pil Sung Yang, Jari Laurikka, Saman Nazarian, Peter W. Macfarlane, Natalia S. Rost, Sekar Kathiresan, Heribert Schunkert, Sandosh Padmanabhan, Tõnu Esko, Bruno H. Stricker, Rebecca Gutmann, Alfredo José Mansur, Jonathan Rosand, Jesper Hastrup Svendsen, Alvaro Alonso, J. Gustav Smith, Benjamin Neumann, John Barnard, Christopher D. Anderson, Joanna Pera, Samir Saba, Lynne J. Hocking, Siew-Kee Low, Daniel I. Chasman, Patrick T. Ellinor, Nancy L. Pedersen, Stephan B. Felix, Vilmundur Gudnason, Kjell Nikus, Kahraman Tanriverdi, David J. Porteous, Samuel C. Dudley, Clive R. Pullinger, Tamara B. Harris, Barry London, Lorenz Risch, Ruth J. F. Loos, Rainer Malik, Isabelle C. Van Gelder, John F. Carlquist, Lena Refsgaard, Carolina Roselli, Albert Y. Sun, Man Li, Lenore J. Launer, Anders Hamsten, Svati H. Shah, Lin Y. Chen, Martina Müller-Nurasyid, Michiel Rienstra, Kent D. Taylor, Katharina Schramm, Jennifer A. Brody, Honghuang Lin, Eric Boerwinkle, Rozenn N. Lemaitre, Olle Melander, Hugh Calkins, Elsayed Z. Soliman, Moritz F. Sinner, Heather L. Bloom, Nicholas L. Smith, Nada Esa, John W. Cole, Maartje N. Niemeijer, David R. Van Wagoner, Anubha Mahajan, Roopinder K. Sandhu, Henry J. Lin, Jordi Jimenez-Conde, Ian Ford, Eue Keun Choi, Stacey Knight, Scott M. Damrauer, Markku Eskola, Claudia Schurman, Stuart A. Scott, Sara L. Pulit, Raymond Noordam, Mika Kähönen, Jay A. Montgomery, Agnieszka Slowik, Esra Gucuk Ipek, Joylene E. Siland, Lingyao Zeng, Andrew P. Morris, Oscar H. Franco, Bas L.J.H. Kietselaer, Adnan Kastrati, Dan E. Arking, José Eduardo Krieger, J. Wouter Jukema, Stefan Gustafsson, Nathan R. Tucker, Zachary T. Yoneda, Daniel Woo, Winfried März, Lauren Margolin, Uwe Völker, Stefan Kääb, Marju Orho-Melander, Lars Lind, Yoichiro Kamatani, Maris Teder-Laving, Paul M. Ridker, Bradford B. Worrall, Jaemin Shim, Bob Weijs, Ingrid E. Christophersen, Kenneth B. Margulies, James P. Cook, Graciela Delgado, Andrea Natale, Stefan Weiss, Gustav Ahlberg, Jie Huang, Guillaume Paré, M. Benjamin Shoemaker, Marcus Dörr, Arnljot Tveit, Elton A. M. P. Dudink, Thomas P. Cappola, Bruce M. Psaty, Alaa Shalaby, Gregory M. Marcus, Sébastien Thériault, Niek Verweij, Traci M. Bartz, Thorsten Kessler, Michael Morley, Xiuqing Guo, Alexandre C. Pereira, Efthymia Vlachopoulou, Albert V. Smith, Andrea R. V. R. Horimoto, David Conen, Erik Ingelsson, Jie Yao, Raul Weiss, David D. McManus, Michiaki Kubo, Lu-Chen Weng, Michael A. Rosenberg, Nona Sotoodehnia, Jennifer E. Huffman, Hui Nam Pak, Dan M. Roden, Peter Weeke, Joshua C. Bis, Archie Campbell, Marta Ribasés, Renee Johnson, Renate B. Schnabel, Christian M. Shaffer, Krishna G. Aragam, Seung Hoan Choi, André G. Uitterlinden, Morten S. Olesen, Toshihiro Tanaka, Daniel J. Rader, Mina K. Chung, Stella Trompet, Steven A. Lubitz, Martin Dichgans, Peter Almgren, Christine M. Albert, Blair H. Smith, Petra Katschnig-Winter, Joshua C. Denny, Christopher Newton-Cheh, Paulus Kirchhof, Namrata Gupta, Emelia J. Benjamin, Stefanie Aeschbacher, Marja-Liisa Lokki, Jorge A. Wong, Quinn S. Wells, Jussi Hernesniemi, Cecilia M. Lindgren, Mark Chaffin, Kaoru Ito, Jerome I. Rotter, Michael J. Cutler, Kerri L. Wiggins, Maryam Kavousi, Nathan A. Bihlmeyer, Bastiaan Geelhoed, Susan R. Heckbert, Caroline Hayward, Alexander Teumer, Paul L. Huang, Terho Lehtimäki, Juha Sinisalo, John P. Kane, Kirsten Leineweber, Tanja Zeller, Hong Euy Lim, Kathryn L. Lunetta, Brian R. Daniels, Heidi Oellers, Biqi Wang, Pim van der Harst, Peter M. Nilsson, Dawood Darbar, Erwin B. Bottinger, Leo-Pekka Lyytikäinen, Epidemiology, Internal Medicine, RS: Carim - H01 Clinical atrial fibrillation, Cardiologie, MUMC+: MA Cardiologie (3), RS: CARIM - R2.01 - Clinical atrial fibrillation, RS: CARIM - R3.11 - Imaging, MUMC+: MA Med Staf Spec Cardiologie (9), MUMC+: MA Med Staf Artsass Cardiologie (9), Cardiovascular Centre (CVC), and MUMC+: MA Cardiologie (9)
Subjects: 0301 basic medicine, medicine.medical_specialty, Identification, Annotation, Quantitative Trait Loci, Genome-wide association study, 030204 cardiovascular system & hematology, Quantitative trait locus, Biology, methods [Genome-Wide Association Study], Gene, genetics [Ethnic Groups], Article, DISEASE, 03 medical and health sciences, COMPONENTS-ANALYSIS, 0302 clinical medicine, ddc:570, Atrial Fibrillation, Cardiac conduction, Ethnicity, Genetics, medicine, Humans, Genetic Predisposition to Disease, genetics [Atrial Fibrillation], Genetic association, Imputation, ethnology [Atrial Fibrillation], Loci, Case-control study, Variants, METANÁLISE, Polymorphic ventricular-tachycardia, 030104 developmental biology, GWAS CATALOG, Susceptibility, Case-Control Studies, Expression quantitative trait loci, genetics [Ethnicity], Medical genetics, Transcriptome, Imputation (genetics), Mutations, Genome-Wide Association Study
Abstract: Atrial fibrillation (AF) affects more than 33 million individuals worldwide 1 and has a complex heritability 2 . We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.
Published: 2018

37. Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries

Author: Rico Rueedi, Yuri Milaneschi, Brenda W.J.H. Penninx, Neil Poulter, Karen Schwander, Marco Brumat, Kenneth Rice, Yize Li, Veronique Vitart, Ioanna Ntalla, Michele K. Evans, Jeffrey R. O'Connell, Nilesh J. Samani, Colleen M. Sitlani, W. James Gauderman, Xuan Deng, Paul M. Ridker, Yun J. Sung, Yukihide Momozawa, Archie Campbell, Tin Louie, Nona Sotoodehnia, Yii-Der Ida Chen, Cornelia M. van Duijn, Tanika N. Kelly, Peter S. Sever, André G. Uitterlinden, Brigitte Kühnel, John M. Starr, Lawrence F. Bielak, Christopher P. Nelson, Wanqing Wen, Stephan B. Felix, Stefan Weiss, Daniel Levy, Nicholette D. Palmer, Alisa K. Manning, Salman M. Tajuddin, Jill M. Norris, Marie Loh, M. Abdullah Said, Alena Stančáková, Anuradhani Kasturiratne, John M. C. Connell, Jian'an Luan, Tuomas O. Kilpeläinen, Amy R. Bentley, Stephen Sidney, Alan B. Zonderman, Karin Leander, David J. Porteous, Jianjun Liu, Tin Aung, Charles B. Eaton, Sharon L.R. Kardia, Rajkumar Dorajoo, Stephen Turner, Michael Boehnke, Diane M. Becker, Cora E. Lewis, Ozren Polasek, Mickaël Canouil, Kurt Lohman, Georg Ehret, Sarah E. Harris, Robert A. Scott, Claude Bouchard, Lynne E. Wagenknecht, Mohsen Ghanbari, Stephen B. Kritchevsky, Jin-Fang Chai, Gregory L. Burke, Jiang He, Federica Laguzzi, Michael R. Brown, Walter Palmas, Lili Milani, Thomas T. Perls, Tibor V. Varga, José Eduardo Krieger, Erin B. Ware, Tamara B. Harris, Tomohiro Katsuya, Nicole Schupf, Mika Kähönen, Nana Matoba, Hugues Aschard, Ilaria Gandin, Jennifer A. Smith, Traci M. Bartz, James Scott, Tuomo Rankinen, Yuan Shi, Meian He, Timo A. Lakka, Helen R. Warren, Mike A. Nalls, Kent D. Taylor, Woon-Puay Koh, Ya Xing Wang, Muhammad Riaz, Sandosh Padmanabhan, Mary F. Feitosa, Jost B. Jonas, Paul Elliott, Christian Gieger, Terho Lehtimäki, Kaare Christensen, Maris Alver, Pirjo Komulainen, Pamela J. Schreiner, M. Arfan Ikram, David R. Weir, Charles Kooperberg, Oscar H. Franco, Yongmei Liu, Lisa de las Fuentes, Nancy L. Pedersen, Thomas W. Winkler, Bruna Gigante, Göran Hallmans, Ingrid B. Borecki, Shiow Lin, Ian J. Deary, Wei Zheng, Yajuan Wang, Bernardo L. Horta, Heather M. Stringham, Bruce M. Psaty, Paul W. Franks, Weihua Zhang, Nora Franceschini, Adolfo Correa, Nita G. Forouhi, Xiuqing Guo, Fumihiko Takeuchi, L. Adrienne Cupples, William R. Scott, Zoltán Kutalik, He Gao, Nicholas J. Wareham, E. Shyong Tai, Aravinda Chakravarti, C. Charles Gu, Paolo Gasparini, Albertine J. Oldehinkel, Xueling Sim, Norihiro Kato, Evangelos Evangelou, Philippe Froguel, Colin A. McKenzie, Qing Duan, Aldi T. Kraja, Carsten Oliver Schmidt, Bamidele O. Tayo, Xiaofeng Zhu, Thomas Meitinger, Mary K. Wojczynski, Markku Laakso, Mark J. Caulfield, Carl D. Langefeld, Jingzhong Ding, Yechiel Friedlander, Tien Yin Wong, Virginia Fisher, Raymond Noordam, Caizheng Yu, Pim van der Harst, Yik Ying Teo, Ervin R. Fox, Sabanayagam Charumathi, Jonathan Marten, Nicholas Y.Q. Tan, Jerome I. Rotter, Harold Snieder, Karen L. Mohlke, Christine Williams, Olli T. Raitakari, Renée de Mutsert, Lihua Wang, Kathryn Roll, Jingmin Liu, Dongfeng Gu, Wei Zhao, Lynda M. Rose, Michael A. Province, Fernando Pires Hartwig, Rob M. van Dam, Barry I. Freedman, Andres Metspalu, Donald W. Bowden, Andrea R. V. R. Horimoto, Martin Farrall, Frits R. Rosendaal, Rainer Rauramaa, Konstantin Strauch, Albert V. Smith, Yanick Hagemeijer, Michiaki Kubo, Ilja M. Nolte, Tõnu Esko, Yih Chung Tham, Cathy C. Laurie, Antonietta Robino, Anne U. Jackson, Chuan Gao, Dabeeru C. Rao, Xiao-Ou Shu, H. Janaka de Silva, Morris J. Brown, Alanna C. Morrison, Peter J. van der Most, Jian-Min Yuan, Melanie Waldenberger, Leslie J. Raffel, Ulrich John, Fang-Chi Hsu, Reedik Mägi, Solomon K. Musani, Chiea Chuen Khor, Mario Sims, Ruben N. Eppinga, Melissa A. Richard, Yoichiro Kamatani, Changwei Li, Qiuyin Cai, Daniel I. Chasman, Mathilde Boissel, Claudia Langenberg, Sami Heikkinen, Jasmin Divers, Saima Afaq, Wen Bin Wei, Jaspal S. Kooner, Terrence Forrester, Hua Tang, Charles N. Rotimi, Anuj Goel, Annette Peters, Tangchun Wu, Dennis O. Mook-Kanamori, Caroline Hayward, Ching-Yu Cheng, Lisa R. Yanek, Ananda R. Wickremasinghe, Chew-Kiat Heng, Myriam Fornage, Dina Vojinovic, Najaf Amin, Lenore J. Launer, Hugh Watkins, Johanna Kuusisto, Jing Hua Zhao, Barbara V. Howard, Vilmundur Gudnason, Ulrich Broeckel, Eric Boerwinkle, Saskia P. Hagenaars, Dan E. Arking, Peter Vollenweider, Alexandre C. Pereira, Jie Yao, Makoto Hirata, Patricia B. Munroe, Patricia A. Peyser, Jessica D. Faul, Xu Chen, Patrik K. E. Magnusson, John C. Chambers, Tamar Sofer, Marzyeh Amini, Benjamin Lehne, Epidemiology, Erasmus MC other, Neurology, Radiology & Nuclear Medicine, Internal Medicine, Læknadeild (HÍ), Faculty of Medicine (UI), School of Health Sciences (UI), Heilbrigðisvísindasvið (HÍ), Háskóli Íslands (HÍ), University of Iceland (UI), Life Course Epidemiology (LCE), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Cardiovascular Centre (CVC), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Brigham and Women's Hospital [Boston], Harvard Medical School [Boston] (HMS), University of Regensburg, Queen Mary University of London (QMUL), Harbor UCLA Medical Center [Torrance, Ca.], Department of Epidemiology, University of North Carolina [Chapel Hill] (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, Northwestern Polytechnical University [Xi'an] (NPU), Centre for Molecular Epidemiology, National University of Singapore (NUS), Harvard School of Public Health, Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), European Genomic Institute for Diabetes - FR 3508 (EGID), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP), National Institutes of Health [Bethesda] (NIH), The following authors declare commercial private and/or governmental affiliations: Bruce M. Psaty (BMP) serves on the DSMB of a clinical trial funded by Zoll Lifecor and on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. Barbara V. Howard (BVH) has a contract from National Heart, Lung, and Blood Institute (NHLBI). Brenda W.J.H. Penninx (BWJHP) has received research funding (non-related to the work reported here) from Jansen Research and Boehringer Ingelheim. Mike A. Nalls (MAN) is supported by a consulting contract between Data Tecnica International LLC and the National Institute on Aging (NIA), National Institutes of Health (NIH), Bethesda, MD, USA. MAN also consults for Illumina Inc., the Michael J. Fox Foundation, and the University of California Healthcare. MAN also has commercial affiliation with Data Tecnica International, Glen Echo, MD, USA. Mark J. Caulfield (MJC) has commercial affiliation and is Chief Scientist for Genomics England, a UK government company. Oscar H Franco (OHF) is supported by grants from Metagenics (on women's health and epigenetics) and from Nestlé (on child health). Peter S. Sever (PSS) is financial supported from several pharmaceutical companies which manufacture either blood pressure lowering or lipid lowering agents, or both, and consultancy fees. Paul W. Franks (PWF) has been a paid consultant in the design of a personalized nutrition trial (PREDICT) as part of a private-public partnership at Kings College London, UK, and has received research support from several pharmaceutical companies as part of European Union Innovative Medicines Initiative (IMI) projects. Fimlab LTD provided support in the form of salaries for author Terho Lehtimäki (TL) but did not have any additional role in the study design to publish, or preparation of the manuscript. Gen‐info Ltd provided support in the form of salaries for author Ozren Polašek (OP) but did not have any additional role in the study design to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. There are no patents, products in development, or marked products to declare. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., AGES (Age Gene/Environment Susceptibility Reykjavik Study) is approved by the Icelandic National Bioethics Committee, VSN: 00–063. The researchers are indebted to the participants for their willingness to participate in the study. ARIC (Atherosclerosis Risk in Communities): The authors thank the staff and participants of the ARIC study for their important contributions. CARDIA (Coronary Artery Risk Development in Young Adults): This manuscript has been reviewed and approved by CARDIA for scientific content. CHS (Cardiovascular Health Study): A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. IGMM (Institute of Genetics and Molecular Medicine): CROATIA-Korcula: We would like to acknowledge the staff of several institutions in Croatia that supported the field work, including but not limited to The University of Split and Zagreb Medical Schools and the Croatian Institute for Public Health. We would like to acknowledge the invaluable contributions of the recruitment team in Korcula, the administrative teams in Croatia and Edinburgh and the participants. The SNP genotyping for the CROATIA-Korcula cohort was performed in Helmholtz Zentrum München, Neuherberg, Germany. CROATIA-Vis: We would like to acknowledge the staff of several institutions in Croatia that supported the field work, including but not limited to The University of Split and Zagreb Medical Schools, the Institute for Anthropological Research in Zagreb and Croatian Institute for Public Health. The SNP genotyping for the CROATIA-Vis cohort was performed in the core genotyping laboratory of the Wellcome Trust Clinical Research Facility at the Western General Hospital, Edinburgh, Scotland. GS:SFHS: Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6] and the Scottish Funding Council [HR03006]. Genotyping of the GS:SFHS samples was carried out by the Genetics Core Laboratory at the Wellcome Trust Clinical Research Facility, Edinburgh, Scotland. ERF (Erasmus Rucphen Family study): We are grateful to all study participants and their relatives, general practitioners and neurologists for their contributions and to P. Veraart for her help in genealogy, J. Vergeer for the supervision of the laboratory work, P. Snijders for his help in data collection and E.M. van Leeuwen for genetic imputation. GENOA (Genetic Epidemiology Network of Arteriopathy): Genotyping was performed at the Mayo Clinic (Stephen T. Turner, MD, Mariza de Andrade PhD, Julie Cunningham, PhD). We thank Eric Boerwinkle, PhD and Megan L. Grove from the Human Genetics Center and Institute of Molecular Medicine and Division of Epidemiology, University of Texas Health Science Center, Houston, Texas, USA for their help with genotyping. We would also like to thank the families that participated in the GENOA study. HANDLS (Healthy Aging in Neighborhoods of Diversity across the Life Span): Data analyses for the HANDLS study utilized the high-performance computational resources of the Biowulf Linux cluster at the National Institutes of Health, Bethesda, MD. http://hpc.nih.gov HUFS (Howard University Family Study): We thank the participants of the study. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official view of the National Institutes of Health. HyperGEN (Hypertension Genetic Epidemiology Network): The study involves: University of Utah: (Network Coordinating Center, Field Center, and Molecular Genetics Lab), Univ. of Alabama at Birmingham: (Field Center and Echo Coordinating and Analysis Center), Medical College of Wisconsin: (Echo Genotyping Lab), Boston University: (Field Center), University of Minnesota: (Field Center and Biochemistry Lab), University of North Carolina: (Field Center), Washington University: (Data Coordinating Center), Weil Cornell Medical College: (Echo Reading Center), National Heart, Lung, & Blood Institute. For a complete list of HyperGEN Investigators: http://www.biostat.wustl.edu/hypergen/Acknowledge.html JHS (Jackson Heart Study): The authors wish to thank the staffs and participants of the JHS. MESA (Multi-Ethnic Study of Atherosclerosis): MESA and the MESA SHARe project are conducted in collaboration with MESA investigators. Genotyping was performed at Affymetrix (Santa Clara, California, USA) and the Broad Institute of Harvard and MIT (Boston, Massachusetts, USA) using the Affymetrix Genome-Wide Human SNP Array 6.0. NEO (The Netherlands Epidemiology of Obesity study): The authors of the NEO study thank all individuals who participated in the Netherlands Epidemiology in Obesity study, all participating general practitioners for inviting eligible participants and all research nurses for collection of the data. We thank the NEO study group, Petra Noordijk, Pat van Beelen and Ingeborg de Jonge for the coordination, lab and data management of the NEO study. RS (Rotterdam Study) was funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. The authors are grateful to the study participants, the staff from the Rotterdam Study and the participating general practitioners and pharmacists. The generation and management of GWAS genotype data for the Rotterdam Study was executed by the Human Genotyping Facility of the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands. We thank Pascal Arp, Mila Jhamai, Marijn Verkerk, Lizbeth Herrera, Marjolein Peters and Carolina Medina-Gomez for their help in creating the GWAS database, and Karol Estrada, Yurii Aulchenko and Carolina Medina-Gomez for the creation and analysis of imputed data. WHI (Women’s Health Initiative): The authors thank the WHI investigators and staff for their dedication, and the study participants for making the program possible. A full listing of WHI investigators can be found at: http://www.whi.org/researchers/Documents%20%20Write%20a%20Paper/WHI%20Investigator%20Short%20List.pdf Replication: AA-DHS (African American Diabetes Heart Study): The investigators acknowledge the cooperation of our Diabetes Heart Study (DHS) and AA-DHS participants. ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial): We thank all ASCOT trial participants, physicians, nurses, and practices in the participating countries for their important contribution to the study. In particular, we thank Clare Muckian and David Toomey for their help in DNA extraction, storage, and handling. We would also like to acknowledge the Barts and The London Genome Centre staff for genotyping the Exome chip array. P.B.M, M.J.C and H.R.W wish to acknowledge the support of the NIHR Cardiovascular Biomedical Research Centre at Barts and Queen Mary University of London, UK. BBJ (Biobank Japan Project): We thank all the participants, medical coordinators of the cooperating hospitals for collecting samples and clinical information in the project. BRIGHT (British Genetics of Hypertension): The BRIGHT study is extremely grateful to all the patients who participated in the study and the BRIGHT nursing team. P.B.M, M.J.C and H.R.W wish to acknowledge the support of the NIHR Cardiovascular Biomedical Research Centre at Barts and Queen Mary University of London, UK. CoLaus (Cohorte Lausannoise Study): The authors would like to thank all the people who participated in the recruitment of the participants, data collection and validation, particularly Nicole Bonvin, Yolande Barreau, Mathieu Firmann, François Bastardot, Julien Vaucher, Panagiotis Antiochos and Cédric Gubelmann. DESIR (Data from an Epidemiological Study on the Insulin Resistance): The DESIR Study Group is composed of Inserm-U1018 (Paris: B. Balkau, P. Ducimetière, E. Eschwège), Inserm-U367 (Paris: F. Alhenc-Gelas), CHU d’Angers (A. Girault), Bichat Hospital (Paris: F. Fumeron, M. Marre, R. Roussel), CHU de Rennes (F. Bonnet), CNRS UMR-8199 (Lille: A. Bonnefond, P. Froguel), Medical Examination Services (Alençon, Angers, Blois, Caen, Chartres, Chateauroux, Cholet, LeMans, Orléans and Tours), Research Institute for General Medicine (J. Cogneau), the general practitioners of the region and the Cross- Regional Institute for Health (C. Born, E. Caces, M. Cailleau, N. Copin, J.G. Moreau, F. Rakotozafy, J. Tichet, S. Vol). DHS (Diabetes Heart Study): The authors thank the investigators, staff, and participants of the DHS for their valuable contributions. EGCUT Estonian Genome Center—University of Tartu (Estonian Biobank): Data analyzes were carried out in part in the High Performance Computing Center of University of Tartu. EPIC (European Prospective Investigation into Cancer and Nutrition)-Norfolk: We thank all EPIC participants and staff for their contribution to the study. FENLAND (The Fenland Study): We are grateful to all the volunteers for their time and help, and to the General Practitioners and practice staff for assistance with recruitment. We thank the Fenland Study Investigators, Fenland Study Co-ordination team and the Epidemiology Field, Data and Laboratory teams. We further acknowledge support from the Medical research council (MC_UU_12015/1). GeneSTAR (Genetic Studies of Atherosclerosis Risk): We are very grateful to all of our participants for their long-term involvement. GLACIER (Gene x Lifestyle Interactions and Complex Traits Involved in Elevated Disease Risk): We thank the participants, health professionals and data managers involved in the Västerbottens Intervention Project. We are also grateful to the staff of the Northern Sweden Biobank for preparing materials and to K Enqvist and T Johansson (Västerbottens County Council, Umeå, Sweden) for DNA preparation. HCHS/SOL (Hispanic Community Health Study/Study of Latinos): We thank the participants and staff of the HCHS/SOL study for their contributions to this study. HRS (Health & Retirement Study): Our genotyping was conducted by the NIH Center for Inherited Disease Research (CIDR) at Johns Hopkins University. Genotyping quality control and final preparation of the data were performed by the Genetics Coordinating Center at the University of Washington. HyperGEN-AXIOM (Hypertension Genetic Epidemiology Network—Axiom Chip GWAS): We thank the study investigators, staff and participants for their value contributions. INGI (Italian Network Genetic Isolate): We thank all the inhabitants who participated to the projects. InterAct (The EPIC-InterAct Case-Cohort Study): We thank all EPIC participants and staff for their contribution to the study. IRAS (Insulin Resistance Atherosclerosis Study): The authors thank study investigators, staff, and participants for their valuable contributions. KORA (Cooperative Health Research in the Augsburg Region): We thank all KORA participants and staff for their contribution to the study. LBC1921 (Lothian Birth Cohort 1921): We thank the LBC1921 cohort participants and team members who contributed to these studies. Funding from the Biological Sciences Research Council (BBSRC) and Medical Research Council (MRC) is gratefully acknowledged. LBC1936 (Lothian Birth Cohort 1936): We thank the LBC1936 cohort participants and team members who contributed to these studies. Funding from the Biological Sciences Research Council (BBSRC) and Medical Research Council (MRC) is gratefully acknowledged. LifeLines (Lifelines Cohort Study): The authors wish to acknowledge the services of the Lifelines, the contributing research centers delivering data to Lifelines, and all the study participants. The authors wish to acknowledge the services of the Lifelines, the contributing research centers delivering data to Lifelines, and all the study participants. Also, Lifelines acknowledges the contributions from Behrooz Z Alizadeh (Department of Epidemiology, University of Groningen, University Medical Center Groningen, The Netherlands), H Marike Boezen (Department of Epidemiology, University of Groningen, University Medical Center Groningen, The Netherlands), Lude Franke (Department of Genetics, University of Groningen, University Medical Center Groningen, The Netherlands), Pim van der Harst (Department of Cardiology, University of Groningen, University Medical Center Groningen, The Netherlands), Gerjan Navis (Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, The Netherlands), Marianne Rots (Department of Medical Biology, University of Groningen, University Medical Center Groningen, The Netherlands), Harold Snieder (Department of Epidemiology, University of Groningen, University Medical Center Groningen, The Netherlands), Morris Swertz (Department of Genetics, University of Groningen, University Medical Center Groningen, The Netherlands), Bruce HR Wolffenbuttel (Department of Endocrinology, University of Groningen, University Medical Center Groningen, The Netherlands), Cisca Wijmenga (Department of Genetics, University of Groningen, University Medical Center Groningen, The Netherlands). LLFS (Long Life Family Study): The LLFS would like to thank the participants and research staff who make the study possible. LOLIPOP (London Life Sciences Prospective Population Study): We acknowledge support of the MRC-PHE Centre for Environment and Health, and the NIHR Health Protection Research Unit on Health Impact of Environmental Hazards. The work was carried out in part at the NIHR/Wellcome Trust Imperial Clinical Research Facility. The views expressed are those of the author(s) and not necessarily those of the Imperial College Healthcare NHS Trust, the NHS, the NIHR or the Department of Health. We thank the participants and research staff who made the study possible. PROCARDIS (Precocious Coronary Artery Disease): The PROCARDIS researchers thank the patients for their selfless participation in this project. RHS (Ragama Health Study): The RHS was supported by the Grant of National Center for Global Health and Medicine (NCGM), Japan. SWHS/SMHS (Shanghai Women's Health Study/ Shanghai Men's Health Study): We thank all the individuals who took part in these studies and all the researchers who have enabled this work to be carried out. TRAILS (TRacking Adolescents’ Individual Lives Survey): TRAILS is a collaborative project involving various departments of the University Medical Center and University of Groningen, the Erasmus University Medical Center Rotterdam, the University of Utrecht, the Radboud Medical Center Nijmegen, and the Parnassia Bavo group, all in the Netherlands. We are grateful to all adolescents who participated in this research and to everyone who worked on this project and made it possible. UKB (United Kingdom Biobank, www.ukbiobank.ac.uk): This research has been conducted using the UK Biobank Resource. The UK Biobank data were analyzed from the data set corresponding to UK Biobank access application no. 236, application title 'Genome-wide association study of blood pressure', with Paul Elliott as the PI/applicant. This work was supported by the UK-CMC and the BP working group., InterAct Consortium, Marten, Jonathan [0000-0001-6916-2014], Luan, Jian'an [0000-0003-3137-6337], Zhao, Jing Hua [0000-0003-4930-3582], Forouhi, Nita [0000-0002-5041-248X], Langenberg, Claudia [0000-0002-5017-7344], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Lee Kong Chian School of Medicine (LKCMedicine), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 (EGID), 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-Centre National de la Recherche Scientifique (CNRS), Feitosa, Mary F., Kraja, Aldi T., Chasman, Daniel I., Sung, Yun J., Winkler, Thomas W., Ntalla, Ioanna, Guo, Xiuqing, Franceschini, Nora, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Marten, Jonathan, Musani, Solomon K., Li, Changwei, Bentley, Amy R., Brown, Michael R., Schwander, Karen, Richard, Melissa A., Noordam, Raymond, Aschard, Hugue, Bartz, Traci M., Bielak, Lawrence F., Dorajoo, Rajkumar, Fisher, Virginia, Hartwig, Fernando P., Horimoto, Andrea R. V. R., Lohman, Kurt K., Manning, Alisa K., Rankinen, Tuomo, Smith, Albert V., Tajuddin, Salman M., Wojczynski, Mary K., Alver, Mari, Boissel, Mathilde, Cai, Qiuyin, Campbell, Archie, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E., He, Meian, Hsu, Fang-Chi, Jackson, Anne U., Kähönen, Mika, Kasturiratne, Anuradhani, Komulainen, Pirjo, Kühnel, Brigitte, Laguzzi, Federica, Luan, Jian'An, Matoba, Nana, Nolte, Ilja M., Padmanabhan, Sandosh, Riaz, Muhammad, Rueedi, Rico, Robino, Antonietta, Said, M. Abdullah, Scott, Robert A., Sofer, Tamar, Stančáková, Alena, Takeuchi, Fumihiko, Tayo, Bamidele O., Van Der Most, Peter J., Varga, Tibor V., Vitart, Veronique, Wang, Yajuan, Ware, Erin B., Warren, Helen R., Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R., Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Amin, Najaf, Amini, Marzyeh, Arking, Dan E., Aung, Tin, Boerwinkle, Eric, Borecki, Ingrid, Broeckel, Ulrich, Brown, Morri, Brumat, Marco, Burke, Gregory L., Canouil, Mickaël, Chakravarti, Aravinda, Charumathi, Sabanayagam, Chen, Yii-Der Ida, Connell, John M., Correa, Adolfo, De Las Fuentes, Lisa, De Mutsert, Renée, De Silva, H. Janaka, Deng, Xuan, Ding, Jingzhong, Duan, Qing, Eaton, Charles B., Ehret, Georg, Eppinga, Ruben N., Evangelou, Evangelo, Faul, Jessica D., Felix, Stephan B., Forouhi, Nita G., Forrester, Terrence, Franco, Oscar H., Friedlander, Yechiel, Gandin, Ilaria, Gao, He, Ghanbari, Mohsen, Gigante, Bruna, Gu, C. Charle, Gu, Dongfeng, Hagenaars, Saskia P., Hallmans, Göran, Harris, Tamara B., He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hirata, Makoto, Howard, Barbara V., Ikram, M. Arfan, John, Ulrich, Katsuya, Tomohiro, Khor, Chiea Chuen, Kilpeläinen, Tuomas O., Koh, Woon-Puay, Krieger, José E., Kritchevsky, Stephen B., Kubo, Michiaki, Kuusisto, Johanna, Lakka, Timo A., Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Lehne, Benjamin, Lewis, Cora E., Li, Yize, Lin, Shiow, Liu, Jianjun, Liu, Jingmin, Loh, Marie, Louie, Tin, Mägi, Reedik, Mckenzie, Colin A., Meitinger, Thoma, Metspalu, Andre, Milaneschi, Yuri, Milani, Lili, Mohlke, Karen L., Momozawa, Yukihide, Nalls, Mike A., Nelson, Christopher P., Sotoodehnia, Nona, Norris, Jill M., O'Connell, Jeff R., Palmer, Nicholette D., Perls, Thoma, Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Poulter, Neil, Raffel, Leslie J., Raitakari, Olli T., Roll, Kathryn, Rose, Lynda M., Rosendaal, Frits R., Rotter, Jerome I., Schmidt, Carsten O., Schreiner, Pamela J., Schupf, Nicole, Scott, William R., Sever, Peter S., Shi, Yuan, Sidney, Stephen, Sims, Mario, Sitlani, Colleen M., Smith, Jennifer A., Snieder, Harold, Starr, John M., Strauch, Konstantin, Stringham, Heather M., Tan, Nicholas Y. Q., Tang, Hua, Taylor, Kent D., Teo, Yik Ying, Tham, Yih Chung, Turner, Stephen T., Uitterlinden, André G., Vollenweider, Peter, Waldenberger, Melanie, Wang, Lihua, Wang, Ya Xing, Wei, Wen Bin, Williams, Christine, Yao, Jie, Yu, Caizheng, Yuan, Jian-Min, Zhao, Wei, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., Chambers, John C., Deary, Ian J., Esko, Tõnu, Farrall, Martin, Franks, Paul W., Freedman, Barry I., Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Jonas, Jost Bruno, Kamatani, Yoichiro, Kato, Norihiro, Kooner, Jaspal S., Kutalik, Zoltán, Laakso, Markku, Laurie, Cathy C., Leander, Karin, Lehtimäki, Terho, Magnusson, Patrik K. E., Oldehinkel, Albertine J., Penninx, Brenda W. J. H., Polasek, Ozren, Porteous, David J., Rauramaa, Rainer, Samani, Nilesh J., Scott, Jame, Shu, Xiao-Ou, Van Der Harst, Pim, Wagenknecht, Lynne E., Wareham, Nicholas J., Watkins, Hugh, Weir, David R., Wickremasinghe, Ananda R., Wu, Tangchun, Zheng, Wei, Bouchard, Claude, Christensen, Kaare, Evans, Michele K., Gudnason, Vilmundur, Horta, Bernardo L., Kardia, Sharon L. R., Liu, Yongmei, Pereira, Alexandre C., Psaty, Bruce M., Ridker, Paul M., Van Dam, Rob M., Gauderman, W. Jame, Zhu, Xiaofeng, Mook-Kanamori, Dennis O., Fornage, Myriam, Rotimi, Charles N., Cupples, L. Adrienne, Kelly, Tanika N., Fox, Ervin R., Hayward, Caroline, Van Duijn, Cornelia M., Tai, E. Shyong, Wong, Tien Yin, Kooperberg, Charle, Palmas, Walter, Rice, Kenneth, Morrison, Alanna C., Elliott, Paul, Caulfield, Mark J., Munroe, Patricia B., Rao, Dabeeru C., Province, Michael A., Levy, Daniel, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Surgery, APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Digital Health, and Ehret, Georg Benedikt
Subjects: Genetics and Molecular Biology (all), Male, Erfðagreining, Áfengissýki, LOCI, Social Sciences, Blood Pressure, Genome-wide association study, Biochemistry, Vascular Medicine, TRANSCRIPTION FACTOR GATA4, Biochemistry, Genetics and Molecular Biology (all), Agricultural and Biological Sciences (all), DEPENDENCE, HEPATOCELLULAR-CARCINOMA, 80 and over, Psychology, Public and Occupational Health, Alcohol consumption, Cardiac and Cardiovascular Systems, Gene–environment interaction, ddc:616, Aged, 80 and over, [STAT.AP]Statistics [stat]/Applications [stat.AP], MESH: Middle Aged, Kardiologi, MESH: Polymorphism, Single Nucleotide, Áfengisneysla, MESH: Gene-Environment Interaction, COMMON VARIANTS, Genomics, MESH: Blood Pressure, Pedigree, 3. Good health, Näringslära, MESH: Young Adult, Physical Sciences, Medicine, Medical genetics, Erfðarannsóknir, Statistics (Mathematics), medicine.medical_specialty, Blood Pressure/genetics, Alcohol Drinking, MESH: Pedigree, Science, Genetic loci, ta3111, Genome Complexity, 03 medical and health sciences, Gene mapping, Genetics, Humans, Polymorphism, Statistical Methods, GENOME-WIDE ASSOCIATION, Molecular Biology Techniques, Molecular Biology, Alleles, Aged, MESH: Adolescent, MESH: Humans, Adolescent, Adult, Alcohol Drinking/epidemiology, Alcohol Drinking/genetics, Cohort Studies, Continental Population Groups/genetics, Continental Population Groups/statistics & numerical data, Female, Gene-Environment Interaction, Genetic Predisposition to Disease/epidemiology, Genetic Predisposition to Disease/genetics, Genome-Wide Association Study, Hypertension/epidemiology, Hypertension/genetics, Middle Aged, Polymorphism, Single Nucleotide, Young Adult, Gene Mapping, Racial Groups, ta1182, Biology and Life Sciences, Computational Biology, MESH: Adult, Meta-analysis, 030104 developmental biology, Genetic Loci, MESH: Genome-Wide Association Study, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], MESH: Female, Mathematics, MESH: Alcohol Drinking, Meta-Analysis, 0301 basic medicine, MESH: Continental Population Groups, MESH: Hypertension, Mathematical and Statistical Techniques, MESH: Aged, 80 and over, Polymorphism (computer science), Medicine and Health Sciences, FUNCTIONAL VARIATION, MESH: Cohort Studies, MESH: Aged, Alcohol Consumption, Multidisciplinary, Nutrition and Dietetics, MESH: Genetic Predisposition to Disease, Genetic Predisposition to Disease/epidemiology/genetics, Single Nucleotide, Blóðþrýstingur, ENVIRONMENT INTERACTION, PTP4A1-PHF3-EYS VARIANTS, Alcoholism, ANCESTRAIS, Háþrýstingur, Hypertension, Blood pressure, [STAT.ME]Statistics [stat]/Methodology [stat.ME], Medical Genetics, Research Article, Substance-Related Disorders, Addiction, RISK, METAANALYSIS, Research and Analysis Methods, Mental Health and Psychiatry, medicine, Medicine [Science], Genetic Predisposition to Disease, Allele, Hypertension/epidemiology/genetics, Nutrition, Medicinsk genetik, Continental Population Groups/genetics/statistics & numerical data, business.industry, Alcohol Drinking/epidemiology/genetics, Genetic architecture, MESH: Male, Introns, Diet, BODY-MASS INDEX, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: Publisher's version (útgefin grein)., Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 x 10−5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10−8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 x 10−8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension., The following authors declare commercial private and/or governmental affiliations: Bruce M. Psaty (BMP) serves on the DSMB of a clinical trial funded by Zoll Lifecor and on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. Barbara V. Howard (BVH) has a contract from National Heart, Lung, and Blood Institute (NHLBI). Brenda W.J.H. Penninx (BWJHP) has received research funding (non-related to the work reported here) from Jansen Research and Boehringer Ingelheim. Mike A. Nalls (MAN) is supported by a consulting contract between Data Tecnica International LLC and the National Institute on Aging (NIA), National Institutes of Health (NIH), Bethesda, MD, USA. MAN also consults for Illumina Inc., the Michael J. Fox Foundation, and the University of California Healthcare. MAN also has commercial affiliation with Data Tecnica International, Glen Echo, MD, USA. Mark J. Caulfield (MJC) has commercial affiliation and is Chief Scientist for Genomics England, a UK government company. Oscar H Franco (OHF) is supported by grants from Metagenics (on women's health and epigenetics) and from Nestlé (on child health). Peter S. Sever (PSS) is financial supported from several pharmaceutical companies which manufacture either blood pressure lowering or lipid lowering agents, or both, and consultancy fees. Paul W. Franks (PWF) has been a paid consultant in the design of a personalized nutrition trial (PREDICT) as part of a private-public partnership at Kings College London, UK, and has received research support from several pharmaceutical companies as part of European Union Innovative Medicines Initiative (IMI) projects. Fimlab LTD provided support in the form of salaries for author Terho Lehtimäki (TL) but did not have any additional role in the study design to publish, or preparation of the manuscript. Gen‐info Ltd provided support in the form of salaries for author Ozren Polašek (OP) but did not have any additional role in the study design to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. There are no patents, products in development, or marked products to declare. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Published: 2018

38. A minimum set of ancestry informative markers for determining admixture proportions in a mixed American population: the Brazilian set

Author: Hadassa Campos Santos, Fernanda Rodrigues-Soares, Maria Fernanda Lima-Costa, Wagner C. S. Magalhães, Nubia Esteban, Eduardo Tarazona-Santos, Thiago Magalhães da Silva, Alexandre C. Pereira, Bernardo L. Horta, Andrea R. V. R. Horimoto, Mauricio Lima Barreto, Maíra R. Rodrigues, Mateus H. Gouveia, Moara Machado, Fernanda S G Kehdy, and José Maurício Sanches
Subjects: Genetic Markers, 0301 basic medicine, Genetic genealogy, Population, Black People, Skin Pigmentation, Single-nucleotide polymorphism, Context (language use), Ancestry-informative marker, Biology, Polymorphism, Single Nucleotide, White People, Article, 03 medical and health sciences, Genotype, Genetics, Humans, education, Genotyping, American Indian or Alaska Native, Genetics (clinical), education.field_of_study, Genome, Human, Pedigree, 030104 developmental biology, Genetic marker, Evolutionary biology, Brazil
Abstract: The Brazilian population is considered to be highly admixed. The main contributing ancestral populations were European and African, with Amerindians contributing to a lesser extent. The aims of this study were to provide a resource for determining and quantifying individual continental ancestry using the smallest number of SNPs possible, thus allowing for a cost- and time-efficient strategy for genomic ancestry determination. We identified and validated a minimum set of 192 ancestry informative markers (AIMs) for the genetic ancestry determination of Brazilian populations. These markers were selected on the basis of their distribution throughout the human genome, and their capacity of being genotyped on widely available commercial platforms. We analyzed genotyping data from 6487 individuals belonging to three Brazilian cohorts. Estimates of individual admixture using this 192 AIM panels were highly correlated with estimates using ~370 000 genome-wide SNPs: 91%, 92%, and 74% of, respectively, African, European, and Native American ancestry components. Besides that, 192 AIMs are well distributed among populations from these ancestral continents, allowing greater freedom in future studies with this panel regarding the choice of reference populations. We also observed that genetic ancestry inferred by AIMs provides similar association results to the one obtained using ancestry inferred by genomic data (370 K SNPs) in a simple regression model with rs1426654, related to skin pigmentation, genotypes as dependent variable. In conclusion, these markers can be used to identify and accurately quantify ancestry of Latin Americans or US Hispanics/Latino individuals, in particular in the context of fine-mapping strategies that require the quantification of continental ancestry in thousands of individuals.
Published: 2015

39. Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation

Author: Joshua C. Bis, Daniel I. Chasman, Archie Campbell, J. Wouter Jukema, Yoichiro Kamatani, Joylene E. Siland, Siegfried Perz, Jie Huang, Jorge A. Wong, Jared W. Magnani, Stefan Weiss, Caroline Hayward, Christopher D. Anderson, Carolina Roselli, Alexander P. Reiner, Maartje N. Niemeijer, Efthymia Vlachopoulou, David R. Van Wagoner, Elsayed Z. Soliman, Lenore J. Launer, Claudia Schurmann, Jeffrey Haessler, Joshua C. Denny, Qiong Yang, Mika Kähönen, Henry J. Lin, Lu-Chen Weng, Molong Li, Paul L. Huang, Terho Lehtimäki, Bruno H. Stricker, Lewin Eisele, Christopher Newton-Cheh, Marcus E. Kleber, Alexander Teumer, Rainer Malik, Juha Sinisalo, Siew-Kee Low, Xiaoyan Yin, Stéphanie Debette, Jennifer A. Brody, Marco V Perez, Derek Klarin, Farid Radmanesh, Ian Ford, Dan M. Roden, Paul M. Ridker, Jan Heeringa, Jonathan Rosand, Andrew P. Morris, Winfried März, Stefan Gustafsson, Xiuqing Guo, Nathan R. Tucker, Dawood Darbar, Daniel J. Rader, Martin Dichgans, Stefan Kääb, Lars Lind, Patrick T. Ellinor, Nancy L. Pedersen, Stefanie Aeschbacher, Erwin B. Bottinger, Leo-Pekka Lyytikäinen, Peter Lichtner, Marcus Dörr, Svati H. Shah, Lin Y. Chen, Alvaro Alonso, Marja-Liisa Lokki, Albert V. Smith, Guillaume Paré, Ruth J. F. Loos, Christine M. Albert, Markku Eskola, Jonathan D. Smith, Kjell Nikus, Martina Müller-Nurasyid, Yanick Hagemeijer, Lorenz Risch, Nona Sotoodehnia, Jussi Hernesniemi, Albert Y. Sun, Man Li, Jemma C. Hopewell, Olle Melander, Albert Hofman, Annette Peters, Pim van der Harst, Michiel Rienstra, Ilkka Seppälä, Kent D. Taylor, Charles Kooperberg, Moritz F. Sinner, Jerome I. Rotter, Stuart A. Scott, Toshihiro Tanaka, Steven A. Lubitz, Uwe Völker, Marju Orho-Melander, Patrik K. E. Magnusson, Jari Laurikka, M. Benjamin Shoemaker, Niek Verweij, J. Gustav Smith, José Eduardo Krieger, Sébastien Thériault, Andrea R. V. R. Horimoto, Natalia S. Rost, André G. Uitterlinden, Oscar H. Franco, David Conen, Cecilia M. Lindgren, Sekar Kathiresan, Michiaki Kubo, Marina Arendt, Graciela Delgado, Anders Hamsten, Rajat Deo, Lars Lannfelt, Sebastian Clauss, Sandosh Padmanabhan, Emelia J. Benjamin, Roopinder K. Sandhu, Bruce M. Psaty, Peter Weeke, Mark Chaffin, Traci M. Bartz, Erik Ingelsson, Alfredo José Mansur, Nathan A. Bihlmeyer, Christian M. Shaffer, Lynne J. Hocking, Stella Trompet, Melanie Waldenberger, Honghuang Lin, Stephan B. Felix, David J. Porteous, Vilmundur Gudnason, Eric Boerwinkle, Dan E. Arking, Alexandre C. Pereira, Bastiaan Geelhoed, Susan R. Heckbert, Jie Yao, Bradford B. Worrall, Ingrid E. Christophersen, Jennifer Kriebel, Peter Almgren, Blair H. Smith, Jennifer E. Huffman, Seung Hoan Choi, Mina K. Chung, Karl-Heinz Jöckel, Yingchang Lu, Yii-Der Ida Chen, Peter W. Macfarlane, John Barnard, Tamara B. Harris, Kathryn L. Lunetta, Stefanie Heilmann-Heimbach, Ganesh Chauhan, Epidemiology, Internal Medicine, and Cardiovascular Centre (CVC)
Subjects: 0301 basic medicine, Quantitative Trait Loci, Medizin, genetics [White People], SNP, Genome-wide association study, 030204 cardiovascular system & hematology, Biology, SUSCEPTIBILITY, Bioinformatics, GENOMAS, ANNOTATION, White People, 03 medical and health sciences, 0302 clinical medicine, ddc:570, Genetic variation, Atrial Fibrillation, Genetics, medicine, Journal Article, TOOL, Humans, Genetic Predisposition to Disease, genetics [Atrial Fibrillation], GENOME-WIDE ASSOCIATION, Stroke, METAANALYSIS, Genetic association, RISK, genetics [Black or African American], GENETIC-VARIATION, Atrial fibrillation, medicine.disease, R1, 3. Good health, Black or African American, genetics [European Continental Ancestry Group], 030104 developmental biology, Genetic Loci, Heart failure, Meta-analysis, VISUALIZATION, genetics [African Americans], BURDEN, Genome-Wide Association Study
Abstract: Atrial fibrillation affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death(1,2). Fourteen genetic loci have been associated with atrial fibrillation in European and Asian ancestry groups(3-7). To further define the genetic basis of atrial fibrillation, we performed large-scale, trans-ancestry meta-analyses of common and rare variant association studies. The genome-wide association studies (GWAS) included 17,931 individuals with atrial fibrillation and 115,142 referents; the exome-wide association studies (ExWAS) and rare variant association studies (RVAS) involved 22,346 cases and 132,086 referents. We identified 12 new genetic loci that exceeded genome-wide significance, implicating genes involved in cardiac electrical and structural remodeling. Our results nearly double the number of known genetic loci for atrial fibrillation, provide insights into the molecular basis of atrial fibrillation, and may facilitate the identification of new potential targets for drug discovery(8).
Published: 2017

40. Timing and quality of sleep in a rural Brazilian family-based cohort, the Baependi Heart Study

Author: Andrea R. V. R. Horimoto, Felipe Beijamini, Tâmara P. Taporoski, André B. Negrão, Alexandre C. Pereira, José Eduardo Krieger, Kieren J. Egan, Homero Vallada, Geraldo Lorenzi-Filho, M. von Schantz, Nubia E. Duarte, Kristen L. Knutson, L. K. G. De Paula, and Mario Pedrazzoli
Subjects: 0301 basic medicine, Gerontology, Adult, Male, Rural Population, Time Factors, Adolescent, Population, Excessive daytime sleepiness, B100, Bedtime, Article, Pittsburgh Sleep Quality Index, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Sex Factors, RA0421, Surveys and Questionnaires, medicine, Humans, Sleep Hygiene, education, Aged, Aged, 80 and over, education.field_of_study, Multidisciplinary, Sleep hygiene, business.industry, Epworth Sleepiness Scale, Age Factors, Chronotype, Middle Aged, Sleep in non-human animals, C800, B900, 030104 developmental biology, Female, medicine.symptom, business, 030217 neurology & neurosurgery, Brazil
Abstract: Sleep is modulated by several factors, including sex, age, and chronotype. It has been hypothesised that contemporary urban populations are under pressure towards shorter sleep duration and poorer sleep quality. Baependi is a small town in Brazil that provides a window of opportunity to study the influence of sleep patterns in a highly admixed rural population with a conservative lifestyle. We evaluated sleep characteristics, excessive daytime sleepiness, and chronotype using the Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale and Morningness-Eveningness Questionnaire questionnaires, respectively. The sample consisted of 1,334 subjects from the Baependi Heart study (41.5% male; age: 46.5 ± 16.2 y, range: 18–89 years). Average self-reported sleep duration was 07:07 ± 01:31 (bedtime 22:32 ± 01:27, wake up time: 06:17 ± 01:25 hh:min), sleep quality score was 4.9 + 3.2, chronotype was 63.6 ± 10.8 and daytime sleepiness was 7.4 ± 4.8. Despite a shift towards morningness in the population, chronotype remained associated with reported actual sleep timing. Age and sex modulated the ontogeny of sleep and chronotype, increasing age was associated with earlier sleep time and shorter sleep duration. Women slept longer and later, and reported poorer sleep quality than men (p
Published: 2016

41. IDENTIFICATION OF NOVEL GWAS HITS FOR SEMANTIC VERBAL FLUENCY: RESULTS FROM A FAMILY-BASED STUDY

Author: Sabine Pompéia, Simon Evans, Nubia E. Duarte, André B. Negrão, Andrea R. V. R. Horimoto, Alexandre C. Pereira, Tâmara P. Taporoski, Homero Vallada, José Eduardo Krieger, and Malcolm von Schantz
Subjects: Pharmacology, Cognition, Genome-wide association study, Heritability, medicine.disease, Psychiatry and Mental health, Neurology, Schizophrenia, Cohort, medicine, Verbal fluency test, Pharmacology (medical), Neurology (clinical), Effects of sleep deprivation on cognitive performance, Association (psychology), Psychology, Biological Psychiatry, Clinical psychology
Abstract: Background Semantic verbal fluency is broadly used in both clinical and non-clinical research, mainly because its sensitivity to several neurobiological conditions associated with cognitive impairment. In order to provide additional insights into genetic component contributing to normal variation on speech production, we conducted a Genome-Wide Association Study (GWAS) of semantic verbal fluency in a family-based cohort from the Baependi Heart Study. Cognitive performance was analysed considering not only the total number of words produced in 60 s but also subdivided into four 15-s time-quartiles because of the involvement of different cognitive processes- predominantly automatic at the beginning and controlled/executive at the end of the task. Methods We analysed cognitive performance of 1,735 participants from 134 extended families (mean age±SD 46±16.2, 60% female). Participants were asked to orally name as many animals as possible within 60 s avoiding repetitions and variations of the same animal. Scores were the numbers of exemplars produced in 60 s, which were broken down into four 15-s time-quartiles [0–15 s (T1), 16–30 s (T2), 31–45 s (T3), 46–60 s (T4)]. Heritability estimates were obtained by an adjusted variance component model. The Baependi cohort was genotyped using different GWAS platforms (custom arrays to capture the tri-ancestry genetic structure of the Brazilian population; Affymetrix Axiom Incor array and Affymetrix SNP chip 6.0; Affymetrix, Santa Clara, CA). Results All performed analysis were adjusted for sex, age, education and time of day since these sociodemographic variables affected means. Heritability calculations showed an estimate of: 60 s=0.21 (p Discussion Using a family-based cohort with a wide distribution of schooling years and, partitioning word production along time-quartiles contributed to the finding of specific genetic markers for verbal fluency at 60 s, T1, T2 e T3. Importantly, the gene influencing score for 60 s (RIMS1) has been previously reported to play a role in cognitive performance and schizophrenia. Our findings provide, on a biological level, grounds for the presence of distinct cognitive processes recruited during semantic verbal fluency since different loci are implicated with each one of the time-intervals.
Published: 2019

42. Cohort profile: the Baependi Heart Study—a family-based, highly admixed cohort study in a rural Brazilian town

Author: Guilherme C Gonçalves, José Eduardo Krieger, Andrea R. V. R. Horimoto, Júlia Maria Pavan Soler, Alexandre C. Pereira, Tâmara P. Taporoski, Mariza de Andrade, Mario Pedrazzoli, Camila Maciel de Oliveira, Hadassa Campos Santos, André B. Negrão, Nubia E. Duarte, Malcolm von Schantz, Rafael de Oliveira Alvim, Geraldo Lorenzi-Filho, Ana Paula Azambuja, Kieren J. Egan, and Homero Vallada
Subjects: 0301 basic medicine, Gerontology, Male, Rural Population, Health Status, Datasets as Topic, Cardiovascular Medicine, Social Environment, Cohort Studies, A900, Risk Factors, Surveys and Questionnaires, Epidemiology, Global health, Ethnicity, education.field_of_study, Anthropometry, General Medicine, Middle Aged, Cardiovascular disease, Circadian Rhythm, Epidemiological transition, Mental Health, Phenotype, Cardiovascular Diseases, Cohort, Female, Brazil, Cohort study, Adult, medicine.medical_specialty, Population, 03 medical and health sciences, medicine, Humans, Family, education, Life Style, Z665, Cohort Profile, business.industry, Mental health, Family design, C800, B900, 030104 developmental biology, Cross-Sectional Studies, business, Sleep
Abstract: PURPOSE: Cardiovascular disease (CVD) is a major challenge to global health. The same epidemiological transition scenario is replayed as countries develop, but with variations based on environment, culture and ethnic mixture. The Baependi Heart Study was set up in 2005 to develop a longitudinal family-based cohort study that reflects on some of the genetic and lifestyle-related peculiarities of the Brazilian populations, in order to evaluate genetic and environmental influences on CVD risk factor traits. PARTICIPANTS: Probands were recruited in Baependi, a small rural town in the state of Minas Gerais, Brazil, following by first-degree and then increasingly more distant relatives. The first follow-up wave took place in 2010, and the second in 2016. At baseline, the study evaluated 1691 individuals across 95 families. Cross-sectional data have been collected for 2239 participants. FINDINGS TO DATE: Environmental and lifestyle factors and measures relevant to cardiovascular health have been reported. Having expanded beyond cardiovascular health outcomes, the phenotype datasets now include genetics, biochemistry, anthropometry, mental health, sleep and circadian rhythms. Many of these have yielded heritability estimates, and a shared genetic background of anxiety and depression has recently been published. In spite of universal access to electricity, the population has been found to be strongly shifted towards morningness compared with metropolitan areas. FUTURE PLANS: A new follow-up, marking 10 years of the study, is ongoing in 2016, in which data are collected as in 2010 (with the exception of the neuropsychiatric protocol). In addition to this, a novel questionnaire package collecting information about intelligence, personality and spirituality is being planned. The data set on circadian rhythms and sleep will be amended through additional questionnaires, actimetry, home sleep EEG recording and dim light melatonin onset (DLMO) analysis. Finally, the anthropometric measures will be expanded by adding three-dimensional facial photography, voice recording and anatomical brain MRI.
Published: 2016

43. Serum metabolomics profile of type 2 diabetes mellitus in a Brazilian rural population

Author: Celso Ronaldo Blatt, Andrea R. V. R. Horimoto, Kallyandra Padilha, Rafael de Oliveira Alvim, José Eduardo Krieger, Alexandre C. Pereira, Gabriela Venturini, Thiago de Farias Pires, Pamella Araujo Malagrino, Tamiris Carneiro Gois, Camila Maciel de Oliveira, and Bianca Kiers
Subjects: 0301 basic medicine, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Metabolite, Clinical Biochemistry, Disease, Type 2 diabetes, Biology, Bioinformatics, 01 natural sciences, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, Metabolomics, Diabetes mellitus, Internal medicine, medicine, 010401 analytical chemistry, Type 2 Diabetes Mellitus, Heritability, medicine.disease, 0104 chemical sciences, 030104 developmental biology, Endocrinology, chemistry, Rural population
Abstract: The development of common forms of diabetes comes from the interaction between environmental and genetic factors, and the consequences of poor glycemic control in these patients could result in several complications. Metabolomic studies for type 2 diabetes mellitus in serum/plasma have reported changes in numerous metabolites, which might be considered possible targets for future mechanistic research. However, the specific role of a particular metabolite as cause or consequence of diabetes derangements is difficult to establish. As type 2 diabetes is a disease that changes the metabolic profile in several levels, this work aimed to compare the metabolomic profiles of type 2 diabetes mellitus and non-diabetic participants. In addition, we exploited our family-based study design to bring a better understanding of the causal relationship of identified metabolites and diabetes. In the current study, population based metabolomics was applied in 939 subjects from the Baependi Heart Study. Participants were separated into two groups: diabetic (77 individuals) and non-diabetic (862 individuals), and the metabolic profile was performed by GC/MS technique. We have identified differentially concentrated metabolites in serum of diabetic and non-diabetic individuals. We identified 72 metabolites up-regulated in type 2 diabetes mellitus compared to non-diabetics. It was possible to recapitulate the main pathways that the literature shows as changed in diabetes. Also, based on metabolomic profile, we separated pre-diabetic individuals (with glucose concentration between 100–125 mg/dL) from non-diabetics and diabetics. Finally, using heritability analysis, we were able to suggest metabolites in which altered levels may precede diabetic development. Our data can be used to derive a better understanding of the causal relationship of the observed associations and help to prioritize diabetes-associated metabolites for further work.
Published: 2016

44. Shared Genetic Factors of Anxiety and Depression Symptoms in a Brazilian Family-Based Cohort, the Baependi Heart Study

Author: Tâmara P. Taporoski, Nubia E. Duarte, Andrea R. V. R. Horimoto, José Eduardo Krieger, Homero Vallada, André B. Negrão, Camila Maciel de Oliveira, Alexandre C. Pereira, Rafael de Oliveira Alvim, and Malcolm von Schantz
Subjects: Adult, Male, medicine.medical_specialty, Population, lcsh:Medicine, Anxiety, Hospital Anxiety and Depression Scale, Social Environment, Cohort Studies, Sex Factors, medicine, Humans, Genetic Predisposition to Disease, Psychiatry, education, lcsh:Science, Depression (differential diagnoses), Genetic association, education.field_of_study, Multidisciplinary, business.industry, Depression, C100, lcsh:R, Heritability, Middle Aged, C800, Pedigree, B900, Phenotype, Cohort, lcsh:Q, Female, Family Relations, medicine.symptom, business, Brazil, Cohort study, Clinical psychology, Research Article, Genome-Wide Association Study
Abstract: To investigate the phenotypic and genetic overlap between anxiety and depression symptoms in an admixed population from extended family pedigrees. Participants (n = 1,375) were recruited from a cohort of 93 families (mean age±SD 42±16.3, 57% female) in the rural town of Baependi, Brazil. The Hospital Anxiety and Depression Scale (HADS) was used to assess depression and anxiety symptoms. Heritability estimates were obtained by an adjusted variance component model. Bivariate analyses were performed to obtain the partition of the covariance of anxiety and depression into genetic and environmental components, and to calculate the genetic contribution modulating both sets of symptoms. Anxiety and depression scores were 7.49±4.01 and 5.70±3.82, respectively. Mean scores were affected by age and were significantly higher in women. Heritability for depression and anxiety, corrected for age and sex, were 0.30 and 0.32, respectively. Significant genetic correlations (ρg = 0.81) were found between anxiety and depression scores; thus, nearly 66% of the total genetic variance in one set of symptoms was shared with the other set. Our results provided strong evidence for a genetic overlap between anxiety and depression symptoms, which has relevance for our understanding of the biological basis of these constructs and could be exploited in genome-wide association studies.
Published: 2015

45. A genome-wide association study of asthma symptoms in Latin American children

Author: Gustavo Nunes de Oliveira Costa, Mauricio Lima Barreto, Dana B. Hancock, Thiago Magalhães da Silva, Bernardo L. Horta, Alexandre C. Pereira, Andrea R. V. R. Horimoto, Maíra R. Rodrigues, Wagner C. S. Magalhães, Stephanie J. London, Isabelle Romieu, Laura C. Rodrigues, Jackson Santos Conceição, Frank Dudbridge, Eduardo Tarazona, Rosemeire L. Fiaccone, Agostino Strina, Maria Fernanda Lima-Costa, Mateus H. Gouveia, Camila Alexandrina Figueiredo, Blanca E. del Rio Navarro, Esteban G. Burchard, Fernanda S G Kehdy, and Maria Pino-Yanes
Subjects: Male, Allergy, Single-nucleotide polymorphism, Genome-wide association study, Biology, Logistic regression, Polymorphism, Single Nucleotide, Genetic model, Genetics, medicine, Humans, Genetic Predisposition to Disease, Genetics(clinical), Child, Children, Genetics (clinical), Genetic association, Asthma, Chromosomes, Human, Pair 14, Principal Component Analysis, Genome-wide association, Asthma symptoms, medicine.disease, 3. Good health, Latin America, Phenotype, Child, Preschool, Expression quantitative trait loci, Female, Metabolic Networks and Pathways, Genome-Wide Association Study, Research Article, Demography
Abstract: Background Asthma is a chronic disease of the airways and, despite the advances in the knowledge of associated genetic regions in recent years, their mechanisms have yet to be explored. Several genome-wide association studies have been carried out in recent years, but none of these have involved Latin American populations with a high level of miscegenation, as is seen in the Brazilian population. Methods 1246 children were recruited from a longitudinal cohort study in Salvador, Brazil. Asthma symptoms were identified in accordance with an International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Following quality control, 1 877 526 autosomal SNPs were tested for association with childhood asthma symptoms by logistic regression using an additive genetic model. We complemented the analysis with an estimate of the phenotypic variance explained by common genetic variants. Replications were investigated in independent Mexican and US Latino samples. Results Two chromosomal regions reached genome-wide significance level for childhood asthma symptoms: the 14q11 region flanking the DAD1 and OXA1L genes (rs1999071, MAF 0.32, OR 1.78, 95 % CI 1.45–2.18, p-value 2.83 × 10−8) and 15q22 region flanking the FOXB1 gene (rs10519031, MAF 0.04, OR 3.0, 95 % CI 2.02–4.49, p-value 6.68 × 10−8 and rs8029377, MAF 0.03, OR 2.49, 95 % CI 1.76–3.53, p-value 2.45 × 10−7). eQTL analysis suggests that rs1999071 regulates the expression of OXA1L gene. However, the original findings were not replicated in the Mexican or US Latino samples. Conclusions We conclude that the 14q11 and 15q22 regions may be associated with asthma symptoms in childhood. Electronic supplementary material The online version of this article (doi:10.1186/s12863-015-0296-7) contains supplementary material, which is available to authorized users.
Published: 2015

46. The search of a genetic basis for noise-induced hearing loss (NIHL)

Author: Lilian Kimura, Regina Célia Mingroni-Netto, Ana Carla Batissoco, Luiz Artur Costa Ricardo, Maria Teresa B. M. Auricchio, Ronaldo Serafim Abreu-Silva, Ary Papa Sguillar, Daniel Rincon, Paulo Alberto Otto, and Andrea R. V. R. Horimoto
Subjects: Adult, Male, Aging, Candidate gene, medicine.medical_specialty, Genotype, Physiology, Epidemiology, Hearing loss, Biology, Audiology, Polymorphism, Single Nucleotide, Connexins, Gene Frequency, Connexin 30, otorhinolaryngologic diseases, Genetics, medicine, Genetic predisposition, Humans, SNP, Genetic Predisposition to Disease, Allele, Hearing Loss, Genetic Association Studies, Glutathione Transferase, Base Sequence, Public Health, Environmental and Occupational Health, Sequence Analysis, DNA, Middle Aged, medicine.disease, Mitochondria, Connexin 26, Haplotypes, Hearing Loss, Noise-Induced, biology.protein, Female, medicine.symptom, Brazil, Noise-induced hearing loss, GJB6
Abstract: Knowledge about the genetic factors responsible for noise-induced hearing loss (NIHL) is still limited. This study investigated whether genetic factors are associated or not to susceptibility to NIHL.The family history and genotypes were studied for candidate genes in 107 individuals with NIHL, 44 with other causes of hearing impairment and 104 controls. Mutations frequently found among deaf individuals were investigated (35delG, 167delT in GJB2, Δ(GJB6- D13S1830), Δ(GJB6- D13S1854) in GJB6 and A1555G in MT-RNR1 genes); allelic and genotypic frequencies were also determined at the SNP rs877098 in DFNB1, of deletions of GSTM1 and GSTT1 and sequence variants in both MTRNR1 and MTTS1 genes, as well as mitochondrial haplogroups.When those with NIHL were compared with the control group, a significant increase was detected in the number of relatives affected by hearing impairment, of the genotype corresponding to the presence of both GSTM1 and GSTT1 enzymes and of cases with mitochondrial haplogroup L1.The findings suggest effects of familial history of hearing loss, of GSTT1 and GSTM1 enzymes and of mitochondrial haplogroup L1 on the risk of NIHL. This study also described novel sequence variants of MTRNR1 and MTTS1 genes.
Published: 2010

47. PENCALC: a program for penetrance estimation in autosomal dominant diseases

Author: Andrea R. V. R. Horimoto, Paulo Alberto Otto, and Márcio T. Onodera
Subjects: Estimation, Genetics, lcsh:QH426-470, Short Communication, Maximum likelihood, maximum likelihood estimation, Pedigree chart, computer.file_format, Biology, Penetrance, lcsh:Genetics, penetrance (rate, value), computer program, Human and Medical Genetics, Credible interval, Executable, penetrance (rate, PROGRAMAÇÃO GENÉTICA, value), Molecular Biology, computer
Abstract: We present a computer program developed for estimating penetrance rates in autosomal dominant diseases by means of family kinship and phenotype information contained within the pedigrees. The program also determines the exact 95% credibility interval for the penetrance estimate. Both executable (PenCalc for Windows) and web versions (PenCalcWeb) of the software are available. The web version enables further calculations, such as heterozygosity probabilities and assessment of offspring risks for all individuals in the pedigrees. Both programs can be accessed and down-loaded freely at the home-page address http://www.ib.usp.br/~otto/software.htm.
Published: 2010

48. Heritability of OSA in a Rural Population

Author: Lilian K.G. de Paula, Rafael de Oliveira Alvim, Alexandre C. Pereira, Camila Maciel de Oliveira, Andrea R. V. R. Horimoto, Rodrigo P. Pedrosa, José Eduardo Krieger, and Geraldo Lorenzi-Filho
Subjects: Pulmonary and Respiratory Medicine, Gerontology, Adult, Male, Population, Inheritance Patterns, Rural Health, Critical Care and Intensive Care Medicine, Body Mass Index, 03 medical and health sciences, 0302 clinical medicine, Sex Factors, Interquartile range, Risk Factors, Covariate, Medicine, Humans, education, education.field_of_study, Sleep Apnea, Obstructive, business.industry, Epworth Sleepiness Scale, Age Factors, Family aggregation, Heritability, Anthropometry, Middle Aged, medicine.disease, Obesity, nervous system diseases, respiratory tract diseases, 030228 respiratory system, Female, Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery, Brazil, Demography
Abstract: Background OSA has a familial aggregation pattern indicating that it can be partially caused by a genetic component. However, the heritability of OSA has been estimated based on the study of families of obese probands of urban populations with established OSA diagnosis. The objective of this genetic-epidemiologic study is to study families ascertained from a general rural population to determine an unbiased estimate of OSA heritability. Methods We studied a sample of families living in Baependi, a small rural southeastern Brazilian city. Participants were assessed for anthropometric measurements, physical examination, Epworth Sleepiness Scale, blood samples for glucose and cholesterol determination, and overnight home portable monitoring. Results We studied 587 participants (399 women) from 91 families, with a median (interquartile range [IQR]) of 4 (2-8) participants per family. The median age of the population was 44 years (IQR, 29-55 years) and median BMI was 25.0 kg/m2 (IQR, 22.1-28.6 kg/m2). OSA, defined by apnea-hypopnea index (AHI) > 5/h, was diagnosed in 18.6% of the sample. Two polygenic models, model I (no covariate effects) and model II (with covariate effects), were fitted to the data in all analyses. Heritability estimates for AHI were 0.23 and 0.25 for model I and II, respectively. Covariates (age, sex, and BMI) showed no significant effects on the heritability estimate for AHI. Conclusions The heritability of AHI in a rural population with low levels of obesity is intermediate (25%).
Published: 2015

49. Glycemic control and arterial stiffness in a Brazilian rural population: Baependi Heart Study

Author: Valéria Aparecida Costa Hong, Andrea R. V. R. Horimoto, Rafael de Oliveira Alvim, Rerisson de Faria Lima, Alexandre C. Pereira, Carlos Alberto Mourão-Júnior, Luiz Aparecido Bortolotto, José Eduardo Krieger, and Camila Maciel de Oliveira
Subjects: medicine.medical_specialty, HbA1c, business.industry, Endocrinology, Diabetes and Metabolism, Research, medicine.disease, Logistic regression, Arterial stiffness, Blood pressure, Glycemic control, Diabetes mellitus, Internal medicine, Internal Medicine, medicine, Cardiology, Risk assessment, business, Pulse wave velocity, Rural population, Glycemic
Abstract: Background Increased arterial stiffness predicts morbidity and mortality, independently of other cardiovascular risk factors, and glycemic control impairments are related to higher vascular stiffness. The aim of this study was to evaluate the association between HbA1c levels and increased arterial stiffness in a Brazilian rural population. Methods For this study were selected 1675 individuals (both genders and aged over 18 years) resident in the municipality of Baependi, a city located in the Southeast of Brazil. HbA1c levels were determined by HPLC. Pulse wave velocity (PWV) was measured with a non-invasive automatic device (Complior). Results HbA1c levels were associated with an increased PWV. This was more relevant for the third tertile of age. In addition, logistic regression multivariate model including age, blood pressure, gender, BMI and fasting glucose showed that the elevation of a single unit percentage of HbA1c represented an increase of 54 % in the odds of increased arterial stiffness [OR 1.54 (95 % CI 1.01–2.17)]. Both, HbA1c and fasting glucose showed higher discriminatory power in the risk assessment for increased arterial stiffness in the non-diabetic when compared to the diabetic group (AUC of HbA1c = 0.71 vs 0.57, p = 0.02; AUC of fasting glucose = 0.66 vs 0.45, p = 0.0007, respectively). Conclusion Our findings indicate that a increase in HbA1c levels is associated with increased arterial stiffness and that both, HbA1c and fasting glucose, presented higher discriminatory power in the risk assessment for increased arterial stiffness in the non-diabetic group as compared to diabetic individuals.
Published: 2015

50. Association between anthropometric indicators of adiposity and hypertension in a Brazilian population: Baependi Heart Study

Author: Fernando Augusto Lavezzo Dias, José Eduardo Krieger, Andrea R. V. R. Horimoto, Anderson Zampier Ulbrich, Camila Maciel de Oliveira, Alexandre C. Pereira, Felipe Silva Neves, and Rafael de Oliveira Alvim
Subjects: Male, Physiology, Cross-sectional study, lcsh:Medicine, Blood Pressure, 030204 cardiovascular system & hematology, Vascular Medicine, Biochemistry, Geographical locations, Body Mass Index, Endocrinology, 0302 clinical medicine, Risk Factors, Medicine and Health Sciences, Diabetes diagnosis and management, 030212 general & internal medicine, lcsh:Science, Abdominal obesity, Adiposity, Aged, 80 and over, Multidisciplinary, Anthropometry, Incidence, Middle Aged, Physiological Parameters, Hypertension, Female, Anatomy, Waist Circumference, medicine.symptom, Brazil, Research Article, Adult, medicine.medical_specialty, HbA1c, Waist, Adolescent, Endocrine Disorders, Intra-Abdominal Fat, Young Adult, 03 medical and health sciences, Internal medicine, Diabetes Mellitus, medicine, Humans, Obesity, Hemoglobin, Aged, business.industry, lcsh:R, Body Weight, Biology and Life Sciences, Proteins, South America, medicine.disease, Diagnostic medicine, Cross-Sectional Studies, Blood pressure, Metabolic Disorders, lcsh:Q, People and places, Metabolic syndrome, business, Body mass index
Abstract: Background Recently, some studies have evaluated the role of adiposity measures in the prediction of hypertension risk, but the results are conflicting. Thus, the aim of this study was to compare which of the four indicators of adiposity (waist circumference–WC, body mass index–BMI, body adiposity index–BAI, and visceral adiposity index–VAI) were better associated with hypertension in a Brazilian population. Methods and findings For this study, were selected 1627 individuals (both genders, and aged over 18 years) resident in the municipality of Baependi, a city located in the Southeast of Brazil. WC, BMI, BAI and VAI were determined according to a standard protocol. Hypertension was defined as mean systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg, and/or antihypertensive drug use. The indicators of adiposity WC, BMI, BAI, and VAI were higher in hypertensive when compared to non-hypertensive individuals. In addition, WC and BMI were most strongly associated with hypertension in men and women, respectively. The area under the curve (AUC) of WC was significantly higher than VAI in men. In women, both AUC of BMI and WC showed higher discriminatory power to predict hypertension than BAI and VAI. Conclusions The indicators of adiposity WC and BMI were better associated with hypertension than BAI and VAI, in both genders, and it could be a useful tools for the screening of hypertensive patients.
Published: 2017

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