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42 results on '"Ntzani EE"'

1. Gender-specific estimates of COPD prevalence: a systematic review and meta-analysis

Author: Ntritsos G, Franek J, Belbasis L, Christou MA, Markozannes G, Altman P, Fogel R, Sayre T, Ntzani EE, and Evangelou E
Subjects: COPD, Prevalence, Meta-Analysis, Diseases of the respiratory system, RC705-779
Abstract: Georgios Ntritsos,1 Jacob Franek,2 Lazaros Belbasis,1 Maria A Christou,1 Georgios Markozannes,1 Pablo Altman,3 Robert Fogel,3 Tobias Sayre,2 Evangelia E Ntzani,1 Evangelos Evangelou1,4 1Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, Ioannina, Greece; 2Doctor Evidence, Client Solutions, Santa Monica, CA, USA; 3Global Medical Affairs, Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 4Department of Epidemiology and Biostatistics, Imperial College London, London, UK Rationale: COPD has been perceived as being a disease of older men. However, >7 million women are estimated to live with COPD in the USA alone. Despite a growing body of literature suggesting an increasing burden of COPD in women, the evidence is limited. Objectives: To assess and synthesize the available evidence among population-based epidemiologic studies and calculate the global prevalence of COPD in men and women. Materials and methods: A systematic review and meta-analysis reporting gender-specific prevalence of COPD was undertaken. Gender-specific prevalence estimates were abstracted from relevant studies. Associated patient characteristics as well as custom variables pertaining to the diagnostic method and other important epidemiologic covariates were also collected. A Bayesian random-effects meta-analysis was performed investigating gender-specific prevalence of COPD stratified by age, geography, calendar time, study setting, diagnostic method, and disease severity. Measurements and main results: Among 194 eligible studies, summary prevalence was 9.23% (95% credible interval [CrI]: 8.16%–10.36%) in men and 6.16% (95% CrI: 5.41%–6.95%) in women. Gender prevalences varied widely by the World Health Organization Global Burden of Disease subregions, with the highest female prevalence found in North America (8.07% vs 7.30%) and in participants in urban settings (13.03% vs 8.34%). Meta-regression indicated that age ≥40 and bronchodilator testing contributed most significantly to heterogeneity of prevalence estimates across studies. Conclusion: We conducted the largest ever systematic review and meta-analysis of global prevalence of COPD and the first large gender-specific review. These results will increase awareness of COPD as a critical woman’s health issue. Keywords: COPD, prevalence, meta-analysis, gender, age, systematic review
Published: 2018

2. HPV infection, cervical abnormalities, and cancer in HIV-infected women in Mumbai, India: 12-month follow-up

Author: Isaakidis P, Pimple S, Varghese B, Khan S, Mansoor H, Ladomirska J, Sharma N, Da Silva E, Metcalf C, Caluwaerts S, Alders P, Ntzani EE, and Reid T
Subjects: Gynecology and obstetrics, RG1-991
Abstract: Petros Isaakidis,1,2 Sharmila Pimple,3 Bhanumati Varghese,1 Samsuddin Khan,1 Homa Mansoor,1 Joanna Ladomirska,1 Neelakumari Sharma,1 Esdras Da Silva,1 Carol Metcalf,4 Severine Caluwaerts,4 Petra Alders,4 Evangelia E Ntzani,2 Tony Reid41Médecins Sans Frontières, Mumbai, India; 2Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece; 3Preventive Oncology Department, Tata Memorial Hospital, Mumbai, India; 4Médecins Sans Frontières, Brussels, BelgiumBackground: HIV-infected women are at a higher risk of cervical intraepithelial neoplasia (CIN) and cancer than women in the general population, partly due to a high prevalence of persistent human papillomavirus (HPV) infection. The aim of the study was to assess the burden of HPV infection, cervical abnormalities, and cervical cancer among a cohort of HIV-infected women as part of a routine screening in an urban overpopulated slum setting in Mumbai, India.Methods: From May 2010 to October 2010, Médecins Sans Frontières and Tata Memorial Hospital Mumbai offered routine annual Pap smears and HPV DNA testing of women attending an antiretroviral therapy (ART) clinic and a 12-month follow-up. Women with abnormal test results were offered cervical biopsy and treatment, including treatment for sexually transmitted infections (STIs).Results: Ninety-five women were screened. Median age was 38 years (IQR: 33–41); median nadir CD4-count 143 cells/µL (IQR: 79–270); and median time on ART 23 months (IQR:10–41). HPV DNA was detected in 30/94 women (32%), and 18/94 (19%) showed either low-grade or high-grade squamous intraepithelial lesions (LSIL/HSIL) on Pap smear. Overall, >50% had cervical inflammatory reactions including STIs. Of the 43 women with a cervical biopsy, eight (8.4%) had CIN-1, five (5.3%) CIN-2, and two (2.1%) carcinoma in situ. All but one had HPV DNA detected (risk ratio: 11, 95% confidence interval: 3.3–34). By October 2011, 56 women had completed the 12-month follow-up and had been rescreened. No new cases of HPV infection/LSIL/HSIL were detected.Conclusion: The high prevalence of HPV infection, STIs, and cervical lesions among women attending an ART clinic demonstrates a need for routine screening. Simple, one-stop screening strategies are needed. The optimal screening interval, especially when resources are limited, needs to be determined.Keywords: HIV/AIDS, HPV, women's health, cervical cancer, operational research, India
Published: 2013

3. Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture

Author: Cummings, Steven, Estrada, K, Styrkarsdottir, U, Evangelou, E, Hsu, YH, Duncan, EL, Ntzani, EE, Oei, L, Albagha, OME, Amin, N, and Kemp, JP
Abstract: Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asi
Published: 2012

4. An atlas of genetic influences on osteoporosis in humans and mice

Author: Morris, JA, Kemp, JP, Youlten, SE, Laurent, L, Logan, JG, Chai, RC, Vulpescu, NA, Forgetta, V, Kleinman, A, Mohanty, ST, Sergio, CM, Quinn, J, Nguyen-Yamamoto, L, Luco, A-L, Vijay, J, Simon, M-M, Pramatarova, A, Medina-Gomez, C, Trajanoska, K, Ghirardello, EJ, Butterfield, NC, Curry, KF, Leitch, VD, Sparkes, PC, Adoum, A-T, Mannan, NS, Komla-Ebri, DSK, Pollard, AS, Dewhurst, HF, Hassall, TAD, Beltejar, M-JG, Agee, M, Alipanahi, B, Auton, A, Bell, RK, Bryc, K, Elson, SL, Fontanillas, P, Furlotte, NA, McCreight, JC, Huber, KE, Litterman, NK, McIntyre, MH, Mountain, JL, Noblin, ES, Northover, CAM, Pitts, SJ, Sathirapongsasuti, JF, Sazonova, OV, Shelton, JF, Shringarpure, S, Tian, C, Tung, JY, Vacic, V, Wilson, CH, Adams, DJ, Vaillancourt, SM, Kaptoge, S, Baldock, P, Cooper, C, Reeve, J, Ntzani, EE, Evangelou, E, Ohlsson, C, Karasik, D, Rivadeneira, F, Kiel, DP, Tobias, JH, Gregson, CL, Harvey, NC, Grundberg, E, Goltzman, D, Lelliott, CJ, Hinds, DA, Ackert-Bicknell, CL, Hsu, Y-H, Maurano, MT, Croucher, PI, Williams, GR, Bassett, JHD, Evans, DM, Richards, JB, Wellcome Trust, and Internal Medicine
Subjects: CHROMATIN, Male, Bone density, Osteoporosis, Genome-wide association study, Fractures, Bone, Mice, 0302 clinical medicine, Bone Density, CALCANEUS, 11 Medical and Health Sciences, Bone mineral, Genetics & Heredity, Mice, Knockout, 0303 health sciences, HERITABILITY, Middle Aged, Phenotype, 3. Good health, Female, BONE-MINERAL DENSITY, Life Sciences & Biomedicine, Adult, medicine.medical_specialty, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, 23andMe Research Team, Article, 03 medical and health sciences, FRACTURES, Internal medicine, Genetics, medicine, Animals, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, METAANALYSIS, HEEL, 030304 developmental biology, Aged, Science & Technology, HIP, Bone fracture, Odds ratio, 06 Biological Sciences, medicine.disease, Endocrinology, QUANTITATIVE ULTRASOUND, 030217 neurology & neurosurgery, Genome-Wide Association Study, Developmental Biology
Abstract: Osteoporosis is a common debilitating chronic disease diagnosed primarily using bone mineral density (BMD). We undertook a comprehensive assessment of human genetic determinants of bone density in 426,824 individuals, identifying a total of 518 genome-wide significant loci, (301 novel), explaining 20% of the total variance in BMD—as estimated by heel quantitative ultrasound (eBMD). Next, meta-analysis identified 13 bone fracture loci in ~1.2M individuals, which were also associated with BMD. We then identified target genes from cell-specific genomic landscape features, including chromatin conformation and accessible chromatin sites, that were strongly enriched for genes known to influence bone density and strength (maximum odds ratio = 58, P = 10-75). We next performed rapid throughput skeletal phenotyping of 126 knockout mice lacking eBMD Target Genes and showed that these mice had an increased frequency of abnormal skeletal phenotypes compared to 526 unselected lines (P < 0.0001). In-depth analysis of one such Target Gene, DAAM2, showed a disproportionate decrease in bone strength relative to mineralization. This comprehensive human and murine genetic atlas provides empirical evidence testing how to link associated SNPs to causal genes, offers new insights into osteoporosis pathophysiology and highlights opportunities for drug development.
Published: 2018

5. Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness

Author: Willems, SM, Wright, DJ, Day, FR, Trajanoska, K, Joshi, PK, Morris, JA, Matteini, AM, Garton, FC, Grarup, N, Oskolkov, N, Thalamuthu, A, Mangino, M, Liu, J, Demirkan, A, Lek, M, Xu, L, Wang, G, Oldmeadow, C, Gaulton, KJ, Lotta, LA, Miyamoto-Mikami, E, Rivas, MA, White, T, Loh, P-R, Aadahl, M, Amin, N, Attia, JR, Austin, K, Benyamin, B, Brage, S, Cheng, Y-C, Cięszczyk, P, Derave, W, Eriksson, K-F, Eynon, N, Linneberg, A, Lucia, A, Massidda, M, Mitchell, BD, Miyachi, M, Murakami, H, Padmanabhan, S, Pandey, A, Papadimitriou, I, Rajpal, DK, Sale, C, Schnurr, TM, Sessa, F, Shrine, N, Tobin, MD, Varley, I, Wain, LV, Wray, NR, Lindgren, CM, MacArthur, DG, Waterworth, DM, McCarthy, MI, Pedersen, O, Khaw, K-T, Kiel, DP, Oei, L, Zheng, H-F, Forgetta, V, Leong, A, Ahmad, OS, Laurin, C, Mokry, LE, Ross, S, Elks, CE, Bowden, J, Warrington, NM, Murray, A, Ruth, KS, Tsilidis, KK, Medina-Gómez, C, Estrada, K, Bis, JC, Chasman, DI, Demissie, S, Enneman, AW, Hsu, Y-H, Ingvarsson, T, Kähönen, M, Kammerer, C, Lacroix, AZ, Li, G, Liu, C-T, Liu, Y, Lorentzon, M, Mägi, R, Mihailov, E, Milani, L, Moayyeri, A, Nielson, CM, Sham, PC, Siggeirsdotir, K, Sigurdsson, G, Stefansson, K, Trompet, S, Thorleifsson, G, Vandenput, L, van der Velde, N, Viikari, J, Xiao, S-M, Zhao, JH, Evans, DS, Cummings, SR, Cauley, J, Duncan, EL, de Groot, LCPGM, Esko, T, Gudnason, V, Harris, TB, Jackson, RD, Jukema, JW, Ikram, AMA, Karasik, D, Kaptoge, S, Kung, AWC, Lehtimäki, T, Lyytikäinen, L-P, Lips, P, Luben, R, Metspalu, A, van Meurs, JBJ, Minster, RL, Orwoll, E, Oei, E, Psaty, BM, Raitakari, OT, Ralston, SW, Ridker, PM, Robbins, JA, Smith, AV, Styrkarsdottir, U, Tranah, GJ, Thorstensdottir, U, Uitterlinden, AG, Zmuda, J, Zillikens, MC, Ntzani, EE, Evangelou, E, Ioannidis, JPA, Evans, DM, Ohlsson, C, Pitsiladis, Y, Fuku, N, Franks, PW, North, KN, van Duijn, CM, Mather, KA, Hansen, T, Hansson, O, Spector, T, Murabito, JM, Richards, JB, Rivadeneira, F, Langenberg, C, Perry, JRB, Wareham, NJ, Scott, RA, Willems, Sara M, Wright, Daniel J, Day, Felix R, Trajanoska, Katerina, Benyamin, Beben, Scott, Robert A, GEFOS Anytype Fracture Consortium, Wright, Daniel [0000-0003-3983-2093], Day, Felix [0000-0003-3789-7651], White, Thomas [0000-0001-8456-0803], Brage, Soren [0000-0002-1265-7355], Khaw, Kay-Tee [0000-0002-8802-2903], Langenberg, Claudia [0000-0002-5017-7344], Perry, John [0000-0001-6483-3771], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Epidemiology, and Internal Medicine
Subjects: Male, Genome-wide association study, VARIANTS, Physical strength, DISEASE, Grip strength, 0302 clinical medicine, Neoplasm Proteins/genetics, GENETIC INFLUENCES, European Continental Ancestry Group/genetics, Aetiology, education.field_of_study, Hand Strength, Deporte, 3. Good health, Neoplasm Proteins, muscular fitness, Science & Technology - Other Topics, Medical genetics, medicine.medical_specialty, Science, 1.1 Normal biological development and functioning, European Continental Ancestry Group, ta3111, Article, White People, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, FRACTURES, Genetics, Humans, GENOME-WIDE ASSOCIATION, Genetik, Polymorphism, education, METAANALYSIS, Aged, VLAG, Global Nutrition, Wereldvoeding, Science & Technology, ta1184, Prevention, Hand/physiology, Biology and Life Sciences, INSTRUMENTS, Hand, GEFOS Any-Type of Fracture Consortium, Nuclear Proteins/genetics, Genetics, Population, 030104 developmental biology, Genetic Loci, 030217 neurology & neurosurgery, 0301 basic medicine, Transforming Growth Factor alpha/genetics, General Physics and Astronomy, Bioinformatics, GROWTH-FACTOR-ALPHA, Cohort Studies, Medicine and Health Sciences, 2.1 Biological and endogenous factors, ta315, Multidisciplinary, Nuclear Proteins, Single Nucleotide, Middle Aged, Multidisciplinary Sciences, MENDELIAN RANDOMIZATION, SKELETAL-MUSCLE, Female, Medical Genetics, Adult, Population, Quantitative trait locus, Biology, Polymorphism, Single Nucleotide, Underpinning research, Hand strength, MD Multidisciplinary, Mendelian randomization, medicine, Life Science, Membrane Proteins/genetics, Deportes, Medicinsk genetik, Repressor Proteins/genetics, Whites, Actins/genetics, Membrane Proteins, General Chemistry, Transforming Growth Factor alpha, Genética, Actins, United Kingdom, Repressor Proteins, Good Health and Well Being, Exercise Physiology and nutrition, Musculoskeletal, genome-wide association, Genome-Wide Association Study
Abstract: Hand grip strength is a widely used proxy of muscular fitness, a marker of frailty, and predictor of a range of morbidities and all-cause mortality. To investigate the genetic determinants of variation in grip strength, we perform a large-scale genetic discovery analysis in a combined sample of 195,180 individuals and identify 16 loci associated with grip strength (P, Hand grip strength as a proxy of muscular fitness is a clinical predictor of mortality and morbidity. In a large-scale GWA study, the authors find 16 robustly associated genetic loci that highlight roles in muscle fibre structure and function, neuronal maintenance and nervous system signal transduction.
Published: 2017

6. Genetic sharing with cardiovascular disease risk factors and diabetes reveals novel bone mineral density loci

Author: Reppe, S, Wang, Y, Thompson, WK, McEvoy, LK, Schork, AJ, Zuber, V, LeBlanc, M, Bettella, F, Mills, IG, Desikan, RS, Djurovic, S, Gautvik, KM, Dale, AM, Andreassen, OA, Estrada, K, Styrkarsdottir, U, Evangelou, E, Hsu, YH, Duncan, EL, Ntzani, EE, Oei, L, Albagha, OME, Amin, N, Kemp, JP, Koller, DL, Li, G, Liu, CT, Minster, RL, Moayyeri, A, Vandenput, L, Willner, D, Xiao, SM, Yerges-Armstrong, LM, Zheng, HF, Alonso, N, Eriksson, J, Kammerer, CM, Kaptoge, SK, Leo, PJ, Thorleifsson, G, Wilson, SG, Wilson, JF, Aalto, V, Alen, M, Aragaki, AK, Aspelund, T, Center, JR, Dailiana, Z, Duggan, DJ, Garcia, M, Garcia-Giralt, N, Giroux, S, Hallmans, G, Hocking, LJ, Husted, LB, Jameson, KA, Khusainova, R, Kim, GS, Kooperberg, C, Koromila, T, Kruk, M, Laaksonen, M, and Lacroix, AZ
Subjects: musculoskeletal diseases, General Science & Technology, MD Multidisciplinary
Abstract: © 2015 Reppe et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Bone Mineral Density (BMD) is a highly heritable trait, but genome-wide association studies have identified few genetic risk factors. Epidemiological studies suggest associations between BMD and several traits and diseases, but the nature of the suggestive comorbidity is still unknown. We used a novel genetic pleiotropy-informed conditional False Discovery Rate (FDR) method to identify single nucleotide polymorphisms (SNPs) associated with BMD by leveraging cardiovascular disease (CVD) associated disorders and metabolic traits. By conditioning on SNPs associated with the CVD-related phenotypes, type 1 diabetes, type 2 diabetes, systolic blood pressure, diastolic blood pressure, high density lipoprotein, low density lipoprotein, triglycerides and waist hip ratio, we identified 65 novel independent BMD loci (26 with femoral neck BMD and 47 with lumbar spine BMD) at conditional FDR < 0.01. Many of the loci were confirmed in genetic expression studies. Genes validated at the mRNA levels were characteristic for the osteoblast/osteocyte lineage, Wnt signaling pathway and bone metabolism. The results provide new insight into genetic mechanisms of variability in BMD, and a better understanding of the genetic underpinnings of clinical comorbidity.
Published: 2015

7. Association between diabetes and exposure to pesticides: a systematic review and meta-analysis

Author: Ntritsos, G, Kavvoura, FK, Chondrogiorgi, M, Ntzani, EE, Tzoulaki, I, and Evangelou, E
Subjects: Endocrinology & Metabolism, Science & Technology, 1117 Public Health And Health Services, 1114 Paediatrics And Reproductive Medicine, 1103 Clinical Sciences, Life Sciences & Biomedicine
Published: 2015

8. New genetic loci link adipose and insulin biology to body fat distribution.

Author: ADIPOGen Consortium, CARDIOGRAMplusC4D Consortium, CKDGen Consortium, GEFOS Consortium, GENIE Consortium, International Endogene Consortium, LifeLines Cohort Study, MAGIC Investigators, MuTHER Consortium, PAGE Consortium, ReproGen Consortium, GLGC, ICBP, Dastani, Z., Hivert, MF., Timpson, N., Perry, JR., Yuan, X., Scott, RA., Henneman, P., Heid, IM., Kizer, JR., Lyytikainen, LP., Fuchsberger, C., Tanaka, T., Morris, AP., Small, K., Isaacs, A., Beekman, M., Coassin, S., Lohman, K., Qi, L., Kanoni, S., Pankow, JS., Uh, HW., Wu, Y., Bidulescu, A., Rasmussen-Torvik, LJ., Greenwood, CM., Ladouceur, M., Grimsby, J., Manning, AK., Liu, CT., Kooner, J., Mooser, VE., Vollenweider, P., Kapur, KA., Chambers, J., Wareham, NJ., Langenberg, C., Frants, R., Willemsvan-vanDijk, K., Oostra, BA., Willems, SM., Lamina, C., Winkler, T., Psaty, BM., Tracy, RP., Brody, J., Chen, I., Viikari, J., Kähönen, M., Pramstaller, PP., Evans, DM., St Pourcain, B., Sattar, N., Wood, A., Bandinelli, S., Carlson, OD., Egan, JM., Böhringer, S., van Heemst, D., Kedenko, L., Kristiansson, K., Nuotio, ML., Loo, BM., Harris, T., Garcia, M., Kanaya, A., Haun, M., Klopp, N., Wichmann, HE., Deloukas, P., Katsareli, E., Couper, DJ., Duncan, BB., Kloppenburg, M., Adair, LS., Borja, JB., Wilson, JG., Musani, S., Guo, X., Johnson, T., Semple, R., Teslovich, TM., Allison, MA., Redline, S., Buxbaum, SG., Mohlke, KL., Meulenbelt, I., Ballantyne, CM., Dedoussis, GV., Hu, FB., Liu, Y., Paulweber, B., Spector, TD., Slagboom, P., Ferrucci, L., Jula, A., Perola, M., Raitakari, O., Florez, JC., Salomaa, V., Eriksson, JG., Frayling, TM., Hicks, AA., Lehtimäki, T., Smith, GD., Siscovick, DS., Kronenberg, F., van Duijn, C., Loos, RJ., Waterworth, DM., Meigs, JB., Dupuis, J., Richards, JB., Willenborg, C., Farrall, M., Assimes, TL., Thompson, JR., Ingelsson, E., Saleheen, D., Erdmann, J., Goldstein, BA., Stirrups, K., König, IR., Cazier, JB., Johansson£££Åsa£££ Å., Hall, AS., Lee, JY., Willer, CJ., Chambers, JC., Esko£££Tõnu£££ T., Folkersen, L., Goel, A., Grundberg, E., Havulinna, AS., Ho, WK., Hopewell, JC., Eriksson, N., Kleber, ME., Lundmark, P., Lyytikäinen, LP., Rafelt, S., Shungin, D., Strawbridge, RJ., Thorleifsson, G., Tikkanen, E., Van Zuydam, N., Voight, BF., Waite, LL., Zhang, W., Ziegler, A., Absher, D., Altshuler, D., Balmforth, AJ., Barroso£££Inês£££ I., Braund, PS., Burgdorf, C., Claudi-Boehm, S., Cox, D., Dimitriou, M., Do, R., Doney, AS., El Mokhtari, N., Eriksson, P., Fischer, K., Fontanillas, P., Franco-Cereceda, A., Gigante, B., Groop, L., Gustafsson, S., Hager, J., Hallmans, G., Han, BG., Hunt, SE., Kang, HM., Illig, T., Kessler, T., Knowles, JW., Kolovou, G., Kuusisto, J., Langford, C., Leander, K., Lokki, ML., Lundmark, A., McCarthy, MI., Meisinger, C., Melander, O., Mihailov, E., Maouche, S., Morris, AD., Müller-Nurasyid, M., Nikus, K., Peden, JF., Rayner, NW., Rasheed, A., Rosinger, S., Rubin, D., Rumpf, MP., Schäfer, A., Sivananthan, M., Song, C., Stewart, AF., Tan, ST., Thorgeirsson, G., van der Schoot CE., Wagner, PJ., Wells, GA., Wild, PS., Yang, TP., Amouyel, P., Arveiler, D., Basart, H., Boehnke, M., Boerwinkle, E., Brambilla, P., Cambien, F., Cupples, AL., de Faire, U., Dehghan, A., Diemert, P., Epstein, SE., Evans, A., Ferrario, MM., Ferrières, J., Gauguier, D., Go, AS., Goodall, AH., Gudnason, V., Hazen, S., Holm, H., Iribarren, C., Jang, Y., Kee, F., Kim, HS., Koenig, W., Kratzer, W., Kuulasmaa, K., Laakso, M., Laaksonen, R., Lind, L., Ouwehand, WH., Parish, S., Park, JE., Pedersen, NL., Peters, A., Quertermous, T., Rader, DJ., Schadt, E., Shah, SH., Sinisalo, J., Stark, K., Stefansson, K., Trégouët, DA., Virtamo, J., Wallentin, L., Wareham, N., Zimmermann, ME., Nieminen, MS., Hengstenberg, C., Sandhu, MS., Pastinen, T., Syvänen, AC., Hovingh, GK., Dedoussis, G., Franks, PW., Metspalu, A., Zalloua, PA., Siegbahn, A., Schreiber, S., Ripatti, S., Blankenberg, SS., Clarke, R., Boehm, BO., O'Donnell, C., Reilly, MP., März, W., Collins, R., Kathiresan, S., Hamsten, A., Kooner, JS., Thorsteinsdottir, U., Danesh, J., Palmer, CN., Roberts, R., Watkins, H., Schunkert, H., Samani, NJ., Pattaro, C., Köttgen, A., Teumer, A., Garnaas, M., Böger, CA., Olden, M., Chen, MH., Tin, A., Taliun, D., Li, M., Gao, X., Gorski, M., Yang, Q., Hundertmark, C., Foster, MC., O'Seaghdha, CM., Glazer, N., Smith, AV., O'Connell, JR., Struchalin, M., Li, G., Johnson, AD., Gierman, HJ., Feitosa, M., Hwang, SJ., Atkinson, EJ., Cornelis, MC., Tönjes, A., Chouraki, V., Holliday, EG., Sorice, R., Kutalik, Z., Deshmukh, H., Ulivi, S., Chu, AY., Murgia, F., Trompet, S., Imboden, M., Kollerits, B., Pistis, G., Harris, TB., Launer, LJ., Aspelund, T., Eiriksdottir, G., Mitchell, BD., Schmidt, H., Cavalieri, M., Rao, M., Demirkan, A., de Andrade, M., Turner, ST., Ding, J., Andrews, JS., Freedman, BI., Döring, A., Wichmann, H-., Kolcic, I., Zemunik, T., Boban, M., Minelli, C., Wheeler, HE., Igl, W., Zaboli, G., Wild, SH., Wright, 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K.L.
Abstract: Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
Published: 2015

9. New genetic loci link adipose and insulin biology to body fat distribution

Author: Shungin, D, Winkler, T, Croteau Chonka, D, Ferreira, T, Locke, A, Mägi, R, Strawbridge, R, Pers, T, Fischer, K, Justice, A, Workalemahu, T, Wu, J, Buchkovich, M, Heard Costa, N, Roman, T, Drong, A, Song, C, Gustafsson, S, Day, F, Esko, T, Fall, T, Kutalik, Z, Luan, J, Randall, J, Scherag, A, Vedantam, S, Wood, A, Chen, J, Fehrmann, R, Karjalainen, J, Kahali, B, Liu, C, Schmidt, E, Absher, D, Amin, N, Anderson, D, Beekman, M, Bragg Gresham, J, Buyske, S, Demirkan, A, Ehret, G, Feitosa, M, Goel, A, Jackson, A, Johnson, T, Kleber, M, Kristiansson, K, Mangino, M, Leach, I, Medina Gomez, C, Palmer, C, Pasko, D, Pechlivanis, S, Peters, M, Prokopenko, I, Stanca'Kova', A, Sung, Y, Tanaka, T, Teumer, A, Van Vliet Ostaptchouk, J, Yengo, L, Zhang, W, Albrecht, E, Ärnlöv, J, Arscott, G, Bandinelli, S, Barrett, A, Bellis, C, Bennett, A, Berne, C, Blüher, M, Böhringer, S, Bonnet, F, Böttcher, Y, Bruinenberg, M, Carba, D, Caspersen, I, Clarke, R, Daw, E, Deelen, J, Deelman, E, Delgado, G, Doney, A, Eklund, N, Erdos, M, Estrada, K, Eury, E, Friedrich, N, Garcia, M, Giedraitis, V, Gigante, B, Go, A, Golay, A, Grallert, H, Grammer, T, Gräsler, J, Grewal, J, Groves, C, Haller, T, Hallmans, G, Hartman, C, Hassinen, M, Hayward, C, Heikkilä, K, Herzig, K, Helmer, Q, Hillege, H, Holmen, O, Hunt, S, Isaacs, A, Ittermann, T, James, A, Johansson, I, Juliusdottir, T, Kalafati, I, Kinnunen, L, Koenig, W, Kooner, I, Kratzer, W, Lamina, C, Leander, K, Lee, N, Lichtner, P, Lind, L, Lindström, J, Lobbens, S, Lorentzon, M, Mach, F, Magnusson, P, Mahajan, A, Mcardle, W, Menni, C, Merger, S, Mihailov, E, Milani, L, Mills, R, Moayyeri, A, Monda, K, Mooijaart, S, Mühleisen, T, Mulas, A, Müller, G, Müller Nurasyid, M, Nagaraja, R, Nalls, M, Narisu, N, Glorioso, N, Nolte, I, Olden, M, Rayner, N, Renstrom, F, Ried, J, Robertson, N, Rose, L, Sanna, S, Scharnagl, H, Scholtens, S, Sennblad, B, Seufferlein, T, Sitlani, C, Smith, A, Stirrups, K, Stringham, H, Sundström, J, Swertz, M, 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Jr, Mosley TH, Seshadri S, Shrine NR, Wain LV, Morken MA, Laitinen J, Zitting P, Cooper JA, van Gilst WH, Janipalli CS, Mani K, Yajnik CS, Mattace Raso FU, Lakatta EG, Orru M, Scuteri A, Ala Korpela M, Kangas AJ, Soininen P, Tukiainen T, Würtz P, Ong RT, Dörr M, Galan P, Hercberg S, Lathrop M, Zelenika D, Zhai G, Meschia JF, Nalls MA, Sharma P, Terzic J, Kumar M, Denniff M, Zukowska Szczechowska E, Wagenknecht LE, Fowkes F, Charchar FJ, Rotimi C, Bots ML, Brand E, Talmud PJ, Nyberg F, Laan M, Palmer LJ, van der Schouw YT, Casas JP, Vineis P, Ganesh SK, Wong TY, Tai ES, Rao DC, Morris RW, Dominiczak AF, Marmot MG, Miki T, Chandak GR, Zhu X, Gyllensten UB, Elosua R, Soranzo N, Sijbrands EJ, Uda M, Vasan RS, Larson MG, Caulfield MJ, Anderson CA, Gordon S, Guo Q, Henders A, Lambert A, Kraft P, Kennedy SH, Macgregor S, Missmer SA, Montgomery GW, Nyholt DR, Painter JN, Roseman F, Treloar SA, Visscher PM, Wallace L, Zondervan KT, Alizadeh B, de Boer RA, Boezen HM, Bruinenberg M, Franke L, Hillege HL, van der Klauw MM, Ormel J, Postma DS, Rosmalen JG, Slaets JP, Stolk RP, Lagou V, Welch RP, Wheeler E, Rehnberg E, Yengo L, Lecoeur C, Johnson PC, Mahajan A, Verweij N, Hottenga JJ, Sennblad B, Salo P, Timpson NJ, Hui J, Bielak LF, Zhao W, Horikoshi M, Navarro P, Fall T, Chen H, Robertson N, Rybin D, Chines PS, Song K, An P, Marullo L, Jansen H, Oldehinkel AJ, North KE, Forouhi NG, Edkins S, Varga TV, Oksa H, Antonella M, Kong A, Herder C, Antti J, Miljkovic I, Atalay M, Kiess W, James AL, Smit JH, Campbell S, Fowkes GR, Basart HV, Rathmann W, Maerz W, Province MA, Watanabe RM, de Geus EJ, Penninx BW, Oostra B, Toenjes A, Peyser PA, Körner A, Keinanen Kiukaanniemi SM, Saaristo TE, Boomsma D, Cucca F, Balkau B, Froguel P, Jarvelin MR, Bouatia Naji N, Ahmadi KR, Ainali C, Barrett A, Bataille V, Bell JT, Buil A, Dermitzakis ET, Dimas AS, Durbin R, Glass D, Hassanali N, Hedman ÅK, Ingle C, Keildson S, Knowles D, Krestyaninova M, Lowe CE, Meduri E, di Meglio P, Min JL, Montgomery SB, Nestle FO, Nica AC, Nisbet J, O'Rahilly S, Parts L, Potter S, Sekowska M, Shin SY, Small KS, Surdulescu G, Travers ME, Tsaprouni L, Tsoka S, Wilk A, Matise T, Buyske S, Higashio J, Williams R, Nato A, Ambite JL, Deelman E, Manolio T, Hindorff L, Heiss G, Taylor K, Avery C, Graff M, Lin D, Quibrera M, Cochran B, Kao L, Umans J, Cole S, MacCluer J, Person S, Pankow J, Gross M, Fornage M, Durda P, Jenny N, Patsy B, Arnold A, Buzkova P, Crawford D, Haines J, Murdock D, Glenn K, Brown Gentry K, Thornton Wells T, Dumitrescu L, Jeff J, Bush WS, Mitchell SL, Goodloe R, Wilson S, Boston J, Malinowski J, Restrepo N, Oetjens M, Fowke J, Zheng W, Spencer K, Ritchie M, Pendergrass S, Le Marchand L, Wilkens L, Park L, Tiirikainen M, Kolonel L, Lim U, Cheng I, Wang H, Shohet R, Haiman C, Stram D, Henderson B, Monroe K, Schumacher F, Peters U, Anderson G, Carlson C, Prentice R, LaCroix A, Wu C, Carty C, Gong J, Rosse S, Young A, Haessler J, Kocarnik J, Lin Y, Jackson R, Duggan D, Kuller L, Stolk L, He C, Sulem P, Barbalic M, Broer L, Byrne EM, Gudbjartsson DF, McArdle PF, Porcu E, van Wingerden S, Zhuang W, Albrecht E, Alizadeh BZ, Lauc LB, Broekmans FJ, Burri A, Chanock SJ, Chen C, Corre T, Coviello AD, d'Adamo P, Davies G, Deary IJ, Ebrahim S, Fauser BC, Ferreli L, Folsom AR, Garcia ME, Hall P, Haller T, Hankinson SE, Hass M, Heath AC, Janssens AC, Keyzer J, Lahti J, Lai S, Laisk T, Laven JS, Liu J, Lopez LM, Louwers YV, Marongiu M, Klaric IM, Masciullo C, McKnight B, Medland SE, Melzer D, Newman AB, Paré G, Peeters PH, Plump AS, Pop VJ, Räikkönen K, Salumets A, Smith JA, Stacey SN, Starr JM, Stathopoulou MG, Tenesa A, Thorand B, Tryggvadottir L, Tsui K, van Dam RM, van Gils CH, van Nierop P, Vink JM, Voorhuis M, Wallaschofski H, Widen E, Wijnands van Gent CJ, Zgaga L, Zygmunt M, Arnold AM, Buring JE, Crisponi L, Demerath EW, Hunter DJ, Schlessinger D, Murray A, Murabito JM, Visser JA, Lunetta KL, Elks CE, Cousminer DL, Feenstra B, Lin P, van Wingerden SW, Smith EN, Warrington NM, Alavere H, Berenson GS, Blackburn H, Busonero F, Chen W, Couper D, Easton DF, Foroud T, Geller F, Hernandez DG, Kilpeläinen TO, Li S, Melbye M, Murray JC, Murray SS, Nelis M, Ness AR, Northstone K, Pennell CE, Pharoah P, Rafnar T, Rice JP, Ring SM, Schork NJ, Segrè AV, Sovio U, Srinivasan SR, Tammesoo ML, Tyrer J, Weedon MN, Wichmann H, Young L, Zhuang WV, Bierut LJ, Boyd HA, and Murray A.
Abstract: Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, we conducted genome-wide association meta-analyses of waist and hip circumference-related traits in up to 224,459 individuals. We identified 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (WHRadjBMI) and an additional 19 loci newly associated with related waist and hip circumference measures (P<5×10-8). Twenty of the 49 WHRadjBMI loci showed significant sexual dimorphism, 19 of which displayed a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation, and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
Published: 2015

10. Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture

Author: Estrada, K, Styrkarsdottir, U, Evangelou, E, Hsu, YH, Duncan, EL, Ntzani, EE, Oei, L, Albagha, OME, Amin, N, Kemp, JP, Koller, DL, Li, G, Liu, CT, Minster, RL, Moayyeri, A, Vandenput, L, Willner, D, Xiao, SM, Yerges-Armstrong, LM, Zheng, HF, Alonso, N, Eriksson, J, Kammerer, CM, Kaptoge, SK, Leo, PJ, Thorleifsson, G, Wilson, SG, Wilson, JF, Aalto, V, Alen, M, Aragaki, AK, Aspelund, T, Center, JR, Dailiana, Z, Duggan, DJ, Garcia, M, Garcia-Giralt, N, Giroux, S, Hallmans, G, Hocking, LJ, Husted, LB, Jameson, KA, Khusainova, R, Kim, GS, Kooperberg, C, Koromila, T, Kruk, M, Laaksonen, M, Lacroix, AZ, Lee, SH, Leung, PC, Lewis, JR, Masi, L, Mencej-Bedrac, S, Nguyen, TV, Nogues, X, Patel, MS, Prezelj, J, Rose, LM, Scollen, S, Siggeirsdottir, K, Smith, AV, Svensson, O, Trompet, S, Trummer, O, Van Schoor, NM, Woo, J, Zhu, K, Balcells, S, Brandi, ML, Buckley, BM, Cheng, S, Christiansen, C, Cooper, C, Dedoussis, G, Ford, I, Frost, M, Goltzman, D, González-Macías, J, Kähönen, M, Karlsson, M, Khusnutdinova, E, Koh, JM, Kollia, P, Langdahl, BL, Leslie, WD, Lips, P, Ljunggren, Ø, Lorenc, RS, Marc, J, Mellström, D, Obermayer-Pietsch, B, Olmos, JM, Pettersson-Kymmer, U, Reid, DM, Riancho, JA, Ridker, PM, Rousseau, F, Lagboom, PES, and Tang, NLS
Subjects: musculoskeletal diseases, Male, Genotype, Quantitative Trait Loci, European Continental Ancestry Group, Mitochondrial Membrane Transport Proteins, Polymorphism, Single Nucleotide, Fractures, Bone, Risk Factors, Bone Density, Humans, Genetic Predisposition to Disease, Glycoproteins, Extracellular Matrix Proteins, Lumbar Vertebrae, Femur Neck, Gene Expression Profiling, Spectrin, Computational Biology, Phosphoproteins, Low Density Lipoprotein Receptor-Related Protein-5, Osteoporosis, Intercellular Signaling Peptides and Proteins, Female, Developmental Biology, Genome-Wide Association Study
Abstract: Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10 -8). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10 -4, Bonferroni corrected), of which six reached P < 5 × 10 -8, including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility. © 2012 Nature America, Inc. All rights reserved.
Published: 2012

11. A meta-analysis of genome-wide association studies identifies novel variants associated with osteoarthritis of the hip

Author: Evangelou, E, Kerkhof, HJ, Styrkarsdottir, U, Ntzani, EE, Bos, SD (Steffan Daniel), Esko, T, Evans, DS, Metrustry, S, Panoutsopoulou, K, Ramos, YFM, Thorleifsson, G, Tsilidis, KK, Arden, N, Aslam, N, Bellamy, N, Birrell, F, Blanco, FJ, Carr, A, Chapman, K, Day-Williams, AG, Deloukas, P, Doherty, M, Engstrom, G, Helgadottir, HT, Hofman, Bert, Ingvarsson, T, Jonsson, H, Keis, A, Keurentjes, JC, Kloppenburg, M, Lind, PA, McCaskie, A, Martin, NG, Milani, L, Montgomery, GW, Nelissen, RGHH, Nevitt, MC, Nilsson, PM, Ollier, WER, Parimi, N, Rai, A, Ralston, SH, Reed, MR, Riancho, JA, Rivadeneira, Fernando, Rodriguez-Fontenla, C, Southam, L, Thorsteinsdottir, U, Tsezou, A, AWallis, G, Wilkinson, JM, Gonzalez, A, Lane, NE, Lohmander, LS, Loughlin, J, Metspalu, A, Uitterlinden, André, Jonsdottir, I, Stefansson, K, Slagboom, PE (Eline), Zeggini, E, Meulenbelt, I, Ioannidis, JPA, Spector, TD, van Meurs, Joyce, Valdes, AM, Evangelou, E, Kerkhof, HJ, Styrkarsdottir, U, Ntzani, EE, Bos, SD (Steffan Daniel), Esko, T, Evans, DS, Metrustry, S, Panoutsopoulou, K, Ramos, YFM, Thorleifsson, G, Tsilidis, KK, Arden, N, Aslam, N, Bellamy, N, Birrell, F, Blanco, FJ, Carr, A, Chapman, K, Day-Williams, AG, Deloukas, P, Doherty, M, Engstrom, G, Helgadottir, HT, Hofman, Bert, Ingvarsson, T, Jonsson, H, Keis, A, Keurentjes, JC, Kloppenburg, M, Lind, PA, McCaskie, A, Martin, NG, Milani, L, Montgomery, GW, Nelissen, RGHH, Nevitt, MC, Nilsson, PM, Ollier, WER, Parimi, N, Rai, A, Ralston, SH, Reed, MR, Riancho, JA, Rivadeneira, Fernando, Rodriguez-Fontenla, C, Southam, L, Thorsteinsdottir, U, Tsezou, A, AWallis, G, Wilkinson, JM, Gonzalez, A, Lane, NE, Lohmander, LS, Loughlin, J, Metspalu, A, Uitterlinden, André, Jonsdottir, I, Stefansson, K, Slagboom, PE (Eline), Zeggini, E, Meulenbelt, I, Ioannidis, JPA, Spector, TD, van Meurs, Joyce, and Valdes, AM
Abstract: Objectives Osteoarthritis (OA) is the most common form of arthritis with a clear genetic component. To identify novel loci associated with hip OA we performed a meta-analysis of genome-wide association studies (GWAS) on European subjects. Methods We performed a two-stage meta-analysis on more than 78 000 participants. In stage 1, we synthesised data from eight GWAS whereas data from 10 centres were used for 'in silico' or 'de novo' replication. Besides the main analysis, a stratified by sex analysis was performed to detect possible sex-specific signals. Meta-analysis was performed using inverse-variance fixed effects models. A random effects approach was also used. Results We accumulated 11 277 cases of radiographic and symptomatic hip OA. We prioritised eight single nucleotide polymorphism (SNPs) for follow-up in the discovery stage (4349 OA cases); five from the combined analysis, two male specific and one female specific. One locus, at 20q13, represented by rs6094710 (minor allele frequency (MAF) 4%) near the NCOA3 (nuclear receptor coactivator 3) gene, reached genome-wide significance level with p=7.9x10(-9) and OR=1.28 (95% CI 1.18 to 1.39) in the combined analysis of discovery (p= 5.6x10(-8)) and follow-up studies (p=7.3x10(-4)). We showed that this gene is expressed in articular cartilage and its expression was significantly reduced in OA-affected cartilage. Moreover, two loci remained suggestive associated; rs5009270 at 7q31 (MAF 30%, p=9.9x10(-7), OR=1.10) and rs3757837 at 7p13 (MAF 6%, p=2.2x10(-6), OR=1.27 in male specific analysis). Conclusions Novel genetic loci for hip OA were found in this meta-analysis of GWAS.
Published: 2014

12. Assessment of Osteoarthritis Candidate Genes in a Meta-Analysis of Nine Genome-Wide Association Studies

Author: Rodriguez-Fontenla, C, Calaza, M, Evangelou, E, Valdes, AM, Arden, N, Blanco, FJ, Carr, A, Chapman, K, Deloukas, P, Doherty, M, Esko, T, Aleta, CMG, Carnota, JJGR, Helgadottir, H, Hofman, Bert, Jonsdottir, I, Kerkhof, HJM, Kloppenburg, M, McCaskie, A, Ntzani, EE, Ollier, WER, Oreiro, N, Panoutsopoulou, K, Ralston, SH, Ramos, YF, Riancho, JA, Rivadeneira, Fernando, Slagboom, PE (Eline), Styrkarsdottir, U, Thorsteinsdottir, U, Thorleifsson, G, Tsezou, A, Uitterlinden, André, Wallis, GA, Wilkinson, JM, Zhai, GJ, Zhu, YY, Felson, DT, Ioannidis, JPA, Loughlin, J, Metspalu, A, Meulenbelt, I, Stefansson, K, van Meurs, Joyce, Zeggini, E, Spector, TD, Gonzalez, A, Rodriguez-Fontenla, C, Calaza, M, Evangelou, E, Valdes, AM, Arden, N, Blanco, FJ, Carr, A, Chapman, K, Deloukas, P, Doherty, M, Esko, T, Aleta, CMG, Carnota, JJGR, Helgadottir, H, Hofman, Bert, Jonsdottir, I, Kerkhof, HJM, Kloppenburg, M, McCaskie, A, Ntzani, EE, Ollier, WER, Oreiro, N, Panoutsopoulou, K, Ralston, SH, Ramos, YF, Riancho, JA, Rivadeneira, Fernando, Slagboom, PE (Eline), Styrkarsdottir, U, Thorsteinsdottir, U, Thorleifsson, G, Tsezou, A, Uitterlinden, André, Wallis, GA, Wilkinson, JM, Zhai, GJ, Zhu, YY, Felson, DT, Ioannidis, JPA, Loughlin, J, Metspalu, A, Meulenbelt, I, Stefansson, K, van Meurs, Joyce, Zeggini, E, Spector, TD, and Gonzalez, A
Abstract: Objective. To assess candidate genes for association with osteoarthritis (OA) and identify promising genetic factors and, secondarily, to assess the candidate gene approach in OA. Methods. A total of 199 candidate genes for association with OA were identified using Human Genome Epidemiology (HuGE) Navigator. All of their single-nucleotide polymorphisms (SNPs) with an allele frequency of > 5% were assessed by fixed-effects meta-analysis of 9 genome-wide association studies (GWAS) that included 5,636 patients with knee OA and 16,972 control subjects and 4,349 patients with hip OA and 17,836 control subjects of European ancestry. An additional 5,921 individuals were genotyped for significantly associated SNPs in the meta-analysis. After correction for the number of independent tests, P values less than 1.58 x 10(-5) were considered significant. Results. SNPs at only 2 of the 199 candidate genes (COL11A1 and VEGF) were associated with OA in the meta-analysis. Two SNPs in COL11A1 showed association with hip OA in the combined analysis: rs4907986 (P = 1.29 x 10(-5), odds ratio [OR] 1.12, 95% confidence interval [95% CI] 1.06 - 1.17) and rs1241164 (P = 1.47 x 10(-5), OR 0.82, 95% CI 0.74 - 0.89). The sex-stratified analysis also showed association of COL11A1 SNP rs4908291 in women (P = 1.29 x 10(-5), OR 0.87, 95% CI 0.82 - 0.92); this SNP showed linkage disequilibrium with rs4907986. A single SNP of VEGF, rs833058, showed association with hip OA in men (P = 1.35 x 10(-5), OR 0.85, 95% CI 0.79 - 0.91). After additional samples were genotyped, association at one of the COL11A1 signals was reinforced, whereas association at VEGF was slightly weakened. Conclusion. Two candidate genes, COL11A1 and VEGF, were significantly associated with OA in this focused meta-analysis. The remaining candidate genes were not associated.
Published: 2014

13. The DOT1L rs12982744 polymorphism is associated with osteoarthritis of the hip with genome- wide statistical significance in males

Author: Evangelou, E, Valdes, AM, Castano Betancourt, Martha, Doherty, M, Doherty, S, Esko, T, Ingvarsson, T, Ioannidis, JPA, Kloppenburg, M, Metspalu, A, Ntzani, EE, Panoutsopoulou, K, Slagboom, PE (Eline), Southam, L, Spector, TD, Styrkarsdottir, U, Stefanson, K, Uitterlinden, André, Wheeler, M, Zeggini, E, Meulenbelt, I, van Meurs, Joyce, Evangelou, E, Valdes, AM, Castano Betancourt, Martha, Doherty, M, Doherty, S, Esko, T, Ingvarsson, T, Ioannidis, JPA, Kloppenburg, M, Metspalu, A, Ntzani, EE, Panoutsopoulou, K, Slagboom, PE (Eline), Southam, L, Spector, TD, Styrkarsdottir, U, Stefanson, K, Uitterlinden, André, Wheeler, M, Zeggini, E, Meulenbelt, I, and van Meurs, Joyce
Published: 2013

14. Genetic effects versus bias for candidate polymorphisms in myocardial infarction: case study and overview of large-scale evidence.

Author: Ntzani EE, Rizos EC, and Ioannidis JP
Abstract: Several genetic polymorphisms have been proposed to be associated with myocardial infarction (MI). The authors examined the evidence and biases underlying such associations using a case-study meta-analysis and an overview of large-scale data. In a meta-analysis of 27 studies addressing the association of the angiotensin type 1 receptor (AT1R)+1166A/C polymorphism with MI (10,180 cases, 17,129 controls), the *C allele conferred an increase in MI risk (odds ratio = 1.13 per allele, p = 0.005). However, there was large between-study heterogeneity; the largest study showed no effect, contradicting smaller studies; and studies with blinded genotyping showed no effect. The authors conducted an overview of meta-analyses of genetic associations for MI or coronary artery disease, including at least three studies and 3,000 subjects. In their latest meta-analysis, another 14 polymorphisms were found to have formally significant associations. If true, these associations would already explain 42% of the MI risk for Caucasian populations. Significant between-study heterogeneity was common. Across the 32 largest studies, only two found formally significant results (nine would be expected if each meta-analysis showed a true association). Even with large-scale evidence from meta-analyses, significant associations for MI may be subject to bias. Large-scale single studies and prospective consortia should be used for detecting and validating the genetic determinants of MI. [ABSTRACT FROM AUTHOR]
Published: 2007
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15. New genetic loci link adipose and insulin biology to body fat distribution

Author: Shungin, Dmitry, Winkler, Thomas W, Workalemahu, Tsegaselassie, Hartman, Catharina A, Duncan, Emma L, Ntzani, Evangelia E, Oei, Ling, Albagha, Omar M E, Amin, Najaf, Kemp, John P, Koller, Daniel L, Li, Guo, Liu, Ching-Ti, Minster, Ryan L, Hassinen, Maija, Moayyeri, Alireza, Vandenput, Liesbeth, Willner, Dana, Xiao, Su-Mei, Yerges-Armstrong, Laura M, Zheng, Hou-Feng, Alonso, Nerea, Eriksson, Joel, Kammerer, Candace M, Kaptoge, Stephen K, Hayward, Caroline, Leo, Paul J, Thorleifsson, Gudmar, Wilson, Scott G, Wilson, James F, Aalto, Ville, Alen, Markku, Aragaki, Aaron K, Aspelund, Thor, Center, Jacqueline R, Dailiana, Zoe, Heikkilä, Kauko, Duggan, David J, Garcia, Melissa, Garcia-Giralt, Natàlia, Giroux, Sylvie, Hallmans, Göran, Hocking, Lynne J, Husted, Lise Bjerre, Jameson, Karen A, Khusainova, Rita, Kim, Ghi Su, Herzig, Karl-Heinz, Kooperberg, Charles, Koromila, Theodora, Kruk, Marcin, Laaksonen, Marika, Lacroix, Andrea Z, Lee, Seung Hun, Leung, Ping C, Lewis, Joshua R, Masi, Laura, Mencej-Bedrac, Simona, Helmer, Quinta, Nguyen, Tuan V, Nogues, Xavier, Patel, Millan S, Prezelj, Janez, Rose, Lynda M, Scollen, Serena, Siggeirsdottir, Kristin, Smith, Albert V, Svensson, Olle, Trompet, Stella, Hillege, Hans L, Trummer, Olivia, van Schoor, Natasja M, Woo, Jean, Zhu, Kun, Balcells, Susana, Brandi, Maria Luisa, Buckley, Brendan M, Cheng, Sulin, Christiansen, Claus, Cooper, Cyrus, Holmen, Oddgeir, Dedoussis, George, Ford, Ian, Frost, Morten, Goltzman, David, González-Macías, Jesús, Kähönen, Mika, Karlsson, Magnus, Khusnutdinova, Elza, Koh, Jung-Min, Kollia, Panagoula, Hunt, Steven C, Langdahl, Bente Lomholt, Leslie, William D, Lips, Paul, Ljunggren, Östen, Lorenc, Roman S, Marc, Janja, Mellström, Dan, Obermayer-Pietsch, Barbara, Olmos, José M, Pettersson-Kymmer, Ulrika, Isaacs, Aaron, Reid, David M, Riancho, José A, Ridker, Paul M, Rousseau, François, Slagboom, P Eline, Tang, Nelson L S, Urreizti, Roser, Van Hul, Wim, Viikari, Jorma, Zarrabeitia, María T, Wu, Joseph M W, Ittermann, Till, Aulchenko, Yurii S, Castano-Betancourt, Martha, Grundberg, Elin, Herrera, Lizbeth, Ingvarsson, Thorvaldur, Johannsdottir, Hrefna, Kwan, Tony, Li, Rui, Luben, Robert, Medina-Gómez, Carolina, James, Alan L, Palsson, Stefan Th, Reppe, Sjur, Rotter, Jerome I, Sigurdsson, Gunnar, van Meurs, Joyce B J, Verlaan, Dominique, Williams, Frances M K, Wood, Andrew R, Zhou, Yanhua, Gautvik, Kaare M, Johansson, Ingegerd, Pastinen, Tomi, Raychaudhuri, Soumya, Cauley, Jane A, Chasman, Daniel I, Clark, Graeme R, Cummings, Steven R, Danoy, Patrick, Dennison, Elaine M, Eastell, Richard, Eisman, John A, Juliusdottir, Thorhildur, Gudnason, Vilmundur, Hofman, Albert, Jackson, Rebecca D, Jones, Graeme, Jukema, J Wouter, Khaw, Kay-Tee, Lehtimäki, Terho, Liu, Yongmei, Lorentzon, Mattias, McCloskey, Eugene, Kalafati, Ioanna-Panagiota, Mitchell, Braxton D, Nandakumar, Kannabiran, Nicholson, Geoffrey C, Oostra, Ben A, Peacock, Munro, Pols, Huibert A P, Prince, Richard L, Raitakari, 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Surdulescu, G., Travers, ME., Tsaprouni, L., Tsoka, S., Wilk, A., Matise, T., Buyske, S., Higashio, J., Williams, R., Nato, A., Ambite, JL., Deelman, E., Manolio, T., Hindorff, L., Heiss, G., Taylor, K., Avery, C., Graff, M., Lin, D., Quibrera, M., Cochran, B., Kao, L., Umans, J., Cole, S., MacCluer, J., Person, S., Pankow, J., Gross, M., Fornage, M., Durda, P., Jenny, N., Patsy, B., Arnold, A., Buzkova, P., Crawford, D., Haines, J., Murdock, D., Glenn, K., Brown-Gentry, K., Thornton-Wells, T., Dumitrescu, L., Jeff, J., Bush, WS., Mitchell, SL., Goodloe, R., Wilson, S., Boston, J., Malinowski, J., Restrepo, N., Oetjens, M., Fowke, J., Zheng, W., Spencer, K., Ritchie, M., Pendergrass, S., Le Marchand£££Loïc£££ L., Wilkens, L., Park, L., Tiirikainen, M., Kolonel, L., Lim, U., Cheng, I., Wang, H., Shohet, R., Haiman, C., Stram, D., Henderson, B., Monroe, K., Schumacher, F., Peters, U., Anderson, G., Carlson, C., Prentice, R., LaCroix, A., Wu, C., Carty, C., Gong, J., Rosse, S., Young, A., Haessler, J., Kocarnik, J., Lin, Y., Jackson, R., Duggan, D., Kuller, L., Stolk, L., He, C., Sulem, P., Barbalic, M., Broer, L., Byrne, EM., Gudbjartsson, DF., McArdle, PF., Porcu, E., van Wingerden, S., Zhuang, W., Albrecht, E., Alizadeh, BZ., Lauc, LB., Broekmans, FJ., Burri, A., Chanock, SJ., Chen, C., Corre, T., Coviello, AD., d'Adamo, P., Davies, G., Deary, IJ., Ebrahim, S., Fauser, BC., Ferreli, L., Folsom, AR., Garcia, ME., Hall, P., Haller, T., Hankinson, SE., Hass, M., Heath, AC., Janssens, AC., Keyzer, J., Lahti, J., Lai, S., Laisk, T., Laven, JS., Liu, J., Lopez, LM., Louwers, YV., Marongiu, M., Klaric, IM., Masciullo, C., McKnight, B., Medland, SE., Melzer, D., Newman, AB., Paré, G., Peeters, PH., Plump, AS., Pop, VJ., Räikkönen, K., Salumets, A., Smith, JA., Stacey, SN., Starr, JM., Stathopoulou, MG., Tenesa, A., Thorand, B., Tryggvadottir, L., Tsui, K., van Dam RM., van Gils CH., van Nierop, P., Vink, JM., Voorhuis, M., Wallaschofski, H., Widen, E., Wijnands-van Gent CJ., Zgaga, L., Zygmunt, M., Arnold, AM., Buring, JE., Crisponi, L., Demerath, EW., Hunter, DJ., Schlessinger, D., Murray, A., Murabito, JM., Visser, JA., Lunetta, KL., Elks, CE., Cousminer, DL., Feenstra, B., Lin, P., van Wingerden SW., Smith, EN., Warrington, NM., Alavere, H., Barroso, I., Berenson, GS., Blackburn, H., Busonero, F., Chen, W., Couper, D., Easton, DF., Foroud, T., Geller, F., Hernandez, DG., Kilpeläinen, TO., Li, S., Melbye, M., Murray, JC., Murray, SS., Nelis, M., Ness, AR., Northstone, K., Pennell, CE., Pharoah, P., Rafnar, T., Rice, JP., Ring, SM., Schork, NJ., Segrè, AV., Sovio, U., Srinivasan, SR., Tammesoo, ML., Tyrer, J., Weedon, MN., Wichmann, H., Young, L., Zhuang, WV., Bierut, LJ., Boyd, HA., Department of Clinical Sciences, Lund University [Lund], Genetic Epidemiology and Clinical Research Group, Umea University Hospital, Department of Odontology, Umeå University, Signalisation et Transports Ioniques Membranaires (STIM), Université de Poitiers-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Department of Medical Sciences, Center for Biological Sequence Analysis [Lyngby], Danmarks Tekniske Universitet = Technical University of Denmark (DTU), Laboratory of Image Science and Technology [Nanjing] (LIST), Southeast University [Jiangsu]-School of Computer Science and Engineering, Limnology, Ecology, Estonian Genome and Medicine, University of Tartu, Institute of Molecular and Cell Biology, Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Department of Medical Genetics, Université de Lausanne = University of Lausanne (UNIL), Institute of Medical Informatics, Biometry and Epidemiology, Universität Duisburg-Essen = University of Duisburg-Essen [Essen], Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Genetic Epidemiology Unit, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Space Sciences Laboratory [Berkeley] (SSL), University of California [Berkeley] (UC Berkeley), University of California (UC)-University of California (UC), Department of Biostatistics and Center for Statistical Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Division of Statistical Genomics, Washington University School of Medicine, King‘s College London, Department of Medicine, University of Eastern Finland-Kuopio University Hospital, Molecular Genetics Section, University of Groningen [Groningen]-University Medical Centre Groningen, Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (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), Geriatric Rehabilitation Unit, Azienda Sanitaria Firenze, Department of Pharmacy Sciences, Creighton University Medical Center, Medical Department III, Universität Leipzig, Foie, métabolismes et cancer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Department of Epidemiology, Erasmus Medical Centre, Netherlands Genomics Initiative (NGI), Netherlands Genomics Initiative, Institute of Epidemiology [Neuherberg] (EPI), German Research Center for Environmental Health - Helmholtz Center München (GmbH), Department of Public Health and Clinical Medicine, Medstar Research Institute, Genetics and Pathology, Finnish Institute of Occupational Health, Epidemiology, University Medical Centre Groningen, Departments of Microbiology & Molecular Genetics and Molecular Biology & Biochemistry, University of California [Irvine] (UC Irvine), Department of Odontology, Cariology, Institute of Human Genetics, Helmholtz Zentrum München = German Research Center for Environmental Health, Génétique des maladies multifactorielles (GMM), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Division of Cardiology, Geneva University Hospital (HUG), Department of Psychiatry and Psychotherapy, Rheinische Friedrich-Wilhelms-Universität Bonn, Department of Physics, Indian Institute of Technology Kanpur (IIT Kanpur), University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), Department of Genomics, Life and Brain Center, Universität Bonn = University of Bonn, Anaesthesia and Intensive care, Royal Aberdeen Childrens Hospital, UCL Institute of neurology, UCL Institute of Neurology, Human Genetics, The Wellcome Trust Sanger Institute [Cambridge], Departments of Epidemiology and Nutrition, Harvard School of Public Health, Institute of Experimental Medicine, Czech Academy of Sciences [Prague] (CAS), Department of Medical Sciences and Uppsala Clinical Research Center, Uppsala University Hospital, Department of Genetics, University of Groningen [Groningen], deCODE Genetics, deCODE genetics [Reykjavik], Pediatric Pulmonology, Allergology & Epidemiology, University of Groningen [Groningen]-University Medical Center Groningen [Groningen] (UMCG)-Beatrix Children's Hospital-Groningen Research Institute for Asthma and COPD, Department of Nutrition-Dietetics, Harokopio University of Athens, Yale School of Medicine [New Haven, Connecticut] (YSM), National Heart and Lung Institute (NHLI), Imperial College London, Queensland Institute of Medical Research, Concord Hospital, Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, Réseau International des Instituts Pasteur (RIIP)-Réseau 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= University of Helsinki, Unit of Genetic Epidemiology and Bioinformatics, Department of Epidemiology, University Medical Center Groningen, Department of Pediatrics, Augusta University - Medical College of Georgia, University System of Georgia (USG)-University System of Georgia (USG), Department of Public Health, South Ostrobothnia Central Hospital, Department of Clinical and Preventive Medicine, Danube-University Krems, Netherlands Consortium for Healthy Aging [Leiden, Netherlands] (NCHA), Institute of Public Health and Clinical Nutrition, University of Eastern Finland, MRC epidemiology Unit, Institute of Epidemiology, Clinical Genetics Branch, Division of Cancer Epidemiology & Genetics, National Institutes of Health [Bethesda] (NIH)-National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Department of Oncology, Queensland Brain Institute, University of Queensland [Brisbane], Harvard Reproductive Sciences Center and Reproductive Endocrine Unit, 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(BU)-National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), Endocrinology and Metabolism, The Churchill Hospital-Oxford Centre for Diabetes, Landsteiner Laboratory, Clinical Haematology, Other departments, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Lund University Diabetes Centre-Lund University [Lund], Université de Tours-Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers, Technical University of Denmark [Lyngby] (DTU), Université de Lausanne (UNIL), Universität Duisburg-Essen [Essen], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), University of California [Berkeley], University of California-University of California, Génomique Intégrative et Modélisation des Maladies Métaboliques (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 Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Universität Leipzig [Leipzig], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), University of California [Irvine] (UCI), German Research Center for Environmental Health, University of Bonn, Czech Academy of Sciences [Prague] (ASCR), Yale University School of Medicine, University of Oxford [Oxford], German Research Center for Environmental Health-Helmholtz-Zentrum München (HZM), Laval University, Laval University [Québec], Turku University Hospital, Lausanne university hospital, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Institut de biologie de Lille - IBL (IBLI), Université de Lille, Sciences et Technologies-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), University of Helsinki-University of Helsinki, Helmholtz-Zentrum München (HZM), National Heart, Lung, and Blood Institute [Bethesda] (NHLBI)-Boston University [Boston] (BU), Internal Medicine, Child and Adolescent Psychiatry / Psychology, Clinical Genetics, Medical Informatics, Obstetrics & Gynecology, Lund University [Lund]-Lund University Diabetes Centre, Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), Institute of Medicine-University of Gothenburg (GU), Signalisation et Transports Ioniques Membranaires ( STIM ), Université de Poitiers-Centre National de la Recherche Scientifique ( CNRS ), Technical University of Denmark [Lyngby] ( DTU ), Laboratory of Image Science and Technology [Nanjing] ( LIST ), Department of Medical Epidemiology and Biostatistics ( MEB ), University of Lausanne, Centre d'Immunologie de Marseille - Luminy ( CIML ), Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Erasmus MC, Space Sciences Laboratory [Berkeley] ( SSL ), Génomique Intégrative et Modélisation des Maladies Métaboliques ( EGID ), Université de Lille-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Pasteur de Lille, Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), University of Leipzig, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institute of Epidemiology [Neuherberg] ( EPI ), University of California [Irvine] ( UCI ), Génétique des maladies multifactorielles ( GMM ), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique ( CNRS ), Geneva University Hospital ( HUG ), Bonn Universität [Bonn], Indian Institute of Technology Kanpur ( IIT Kanpur ), The University of North Carolina at Chapel Hill, Université de Bonn, Wellcome Trust Sanger Institute, Harvard University School of Public Health, Czech Academy of Sciences [Prague] ( ASCR ), deCODE genetics, University of Groningen [Groningen]-University Medical Center Groningen-Beatrix Children's Hospital-Groningen Research Institute for Asthma and COPD, Yale School of Medicine, National Heart and Lung Institute ( NHLI ), Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lille, Droit et Santé, University Medical Center Groningen, University of Cambridge [UK] ( CAM ), Wellcome Trust Centre for Human Genetics, University of Pisa [Pisa], University of Cambridge [UK] ( CAM ) -Institute of Metabolic Science, German Research Center for Environmental Health-Helmholtz-Zentrum München ( HZM ), University of Otago, University of Greifswald, University College of London [London] ( UCL ), National Institute for Health and Welfare, Queen's University [Belfast] ( QUB ), University of Hawaii at Manoa ( UHM ), University of Gothenburg ( GU ) -Institute of Medicine, Recherches en Psychopathologie, nouveaux symptômes et lien social ( EA 4050 ), Université de Poitiers-Université de Brest ( UBO ) -Université Catholique de l'Ouest-Université de Rennes 2 ( UR2 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ), Institut de biologie de Lille - IBL ( IBLI ), Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique ( CNRS ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), University Medicine Greifswald,-HELIOS Hospital Stralsund, Finland Institute for Molecular Medicine ( FIMM ), Georgia Prevention Institute, Netherlands Consortium for Healthy Aging, Helmholtz-Zentrum München ( HZM ), National Institutes of Health ( NIH ) -National Cancer Institute ( NIH ), Massachusetts General Hospital, Children's Hospital, Boston, Broad Institute, Cambridge, MA, The University of North Carolina at Chapel Hill-UNC Gillings School of Global Public Health-Carolina Center for Genome Sciences, Shungin D, Winkler TW, Adipogen, Consortium, Cardiogramplusc4d, Consortium, Ckdgen, Consortium, Gefos, Consortium, Genie, Consortium, Glgc, Icbp, International, Endogene Consortium, Lifelines, Cohort Study, Magic, Investigator, Muther, Consortium, Consortium, Page, ReproGen Consortium, Amouyel P, D'Adamo, ADAMO PIO, Gasparini, Paolo, Shungin, Dmitry, Winkler, Thomas W, Croteau-Chonka, Damien C, Ferreira, Teresa, Hypponen, Elina, Mohlke, Karen L, ADIPOGEN Consortium, Int Endogene Consortium, Lee Kong Chian School of Medicine (LKCMedicine), Epidemiologie, RS: CARIM - R3.02 - Hypertension and target organ damage, Université de Tours-Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biological Psychology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Lifestyle, Overweight and Diabetes, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life Course Epidemiology (LCE), Cardiovascular Centre (CVC), Groningen Kidney Center (GKC), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Groningen Research Institute for Asthma and COPD (GRIAC), Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Center for Liver, Digestive and Metabolic Diseases (CLDM), Stem Cell Aging Leukemia and Lymphoma (SALL), Shungin, D, Winkler, T, Croteau Chonka, D, Ferreira, T, Locke, A, Mägi, R, Strawbridge, R, Pers, T, Fischer, K, Justice, A, Workalemahu, T, Wu, J, Buchkovich, M, Heard Costa, N, Roman, T, Drong, A, Song, C, Gustafsson, S, Day, F, Esko, T, Fall, T, Kutalik, Z, Luan, J, Randall, J, Scherag, A, Vedantam, S, Wood, A, Chen, J, Fehrmann, R, Karjalainen, J, Kahali, B, Liu, C, Schmidt, E, Absher, D, Amin, N, Anderson, D, Beekman, M, Bragg Gresham, J, Buyske, S, Demirkan, A, Ehret, G, Feitosa, M, Goel, A, Jackson, A, Johnson, T, Kleber, M, Kristiansson, K, Mangino, M, Leach, I, Medina Gomez, C, Palmer, C, Pasko, D, Pechlivanis, S, Peters, M, Prokopenko, I, Stanca'Kova', A, Sung, Y, Tanaka, T, Teumer, A, Van Vliet Ostaptchouk, J, Yengo, L, Zhang, W, Albrecht, E, Ärnlöv, J, Arscott, G, Bandinelli, S, Barrett, A, Bellis, C, Bennett, A, Berne, C, Blüher, M, Böhringer, S, Bonnet, F, Böttcher, Y, Bruinenberg, M, Carba, D, Caspersen, I, Clarke, R, Daw, E, Deelen, J, Deelman, E, Delgado, G, Doney, A, Eklund, N, Erdos, M, Estrada, K, Eury, E, Friedrich, N, Garcia, M, Giedraitis, V, Gigante, B, Go, A, Golay, A, Grallert, H, Grammer, T, Gräsler, J, Grewal, J, Groves, C, Haller, T, Hallmans, G, Hartman, C, Hassinen, M, Hayward, C, Heikkilä, K, Herzig, K, Helmer, Q, Hillege, H, Holmen, O, Hunt, S, Isaacs, A, Ittermann, T, James, A, Johansson, I, Juliusdottir, T, Kalafati, I, Kinnunen, L, Koenig, W, Kooner, I, Kratzer, W, Lamina, C, Leander, K, Lee, N, Lichtner, P, Lind, L, Lindström, J, Lobbens, S, Lorentzon, M, Mach, F, Magnusson, P, Mahajan, A, Mcardle, W, Menni, C, Merger, S, Mihailov, E, Milani, L, Mills, R, Moayyeri, A, Monda, K, Mooijaart, S, Mühleisen, T, Mulas, A, Müller, G, Müller Nurasyid, M, Nagaraja, R, Nalls, M, Narisu, N, Glorioso, N, Nolte, I, Olden, M, Rayner, N, Renstrom, F, Ried, J, Robertson, N, Rose, L, Sanna, S, Scharnagl, H, Scholtens, S, Sennblad, B, Seufferlein, T, Sitlani, C, Smith, A, Stirrups, K, Stringham, H, Sundström, J, Swertz, M, Swift, A, Syvänen, A, Tayo, B, Thorand, B, Thorleifsson, G, Tomaschitz, A, Troffa, C, Van Oort, F, Verweij, N, Vonk, J, Waite, L, Wennauer, R, Wilsgaard, T, Wojczynski, M, Wong, A, Zhang, Q, Zhao, J, Brennan, E, Choi, M, Eriksson, P, Folkersen, L, Franco Cereceda, A, Gharavi, A, Hedman, A, Hivert, M, Huang, J, Kanoni, S, Karpe, F, Keildson, S, Kiryluk, K, Liang, L, Lifton, R, Ma, B, Mcknight, A, Mcpherson, R, Metspalu, A, Min, J, Moffatt, M, Montgomery, G, Murabito, J, Nicholson, G, Nyholt, D, Olsson, C, Perry, J, Reinmaa, E, Salem, R, Sandholm, N, Schadt, E, Scott, R, Stolk, L, Vallejo, E, Westra, H, Zondervan, K, Amouyel, P, Arveiler, D, Bakker, S, Beilby, J, Bergman, R, Blangero, J, Brown, M, Burnier, M, Campbell, H, Chakravarti, A, Chines, P, Claudi Boehm, S, Collins, F, Crawford, D, Danesh, J, De Faire, U, De Geus, E, Dörr, M, Erbel, R, Eriksson, J, Farrall, M, Ferrannini, E, Ferrières, J, Forouhi, N, Forrester, T, Franco, O, Gansevoort, R, Gieger, C, Gudnason, V, Haiman, C, Harris, T, Hattersley, A, Heliövaara, M, Hicks, A, Hingorani, A, Hoffmann, W, Hofman, A, Homuth, G, Humphries, S, Hyppönen, E, Illig, T, Jarvelin, M, Johansen, B, Jousilahti, P, Jula, A, Kaprio, J, Kee, F, Keinanen Kiukaanniemi, S, Kooner, J, Kooperberg, C, Kovacs, P, Kraja, A, Kumari, M, Kuulasmaa, K, Kuusisto, J, Lakka, T, Langenberg, C, Le Marchand, L, Lehtimäki, T, Lyssenko, V, Männistö, S, Marette, A, Matise, T, Mckenzie, C, Mcknight, B, Musk, A, Möhlenkamp, S, Morris, A, Nelis, M, Ohlsson, C, Oldehinkel, A, Ong, K, Palmer, L, Penninx, B, Peters, A, Pramstaller, P, Raitakari, O, Rankinen, T, Rao, D, Rice, T, Ridker, P, Ritchie, M, Rudan, I, Salomaa, V, Samani, N, Saramies, J, Sarzynski, M, Schwarz, P, Shuldiner, A, Staessen, J, Steinthorsdottir, V, Stolk, R, Strauch, K, Tönjes, A, Tremblay, A, Tremoli, E, Vohl, M, Völker, U, Vollenweider, P, Wilson, J, Witteman, J, Adair, L, Bochud, M, Boehm, B, Bornstein, S, Bouchard, C, Cauchi, S, Caulfield, M, Chambers, J, Chasman, D, Cooper, R, Dedoussis, G, Ferrucci, L, Froguel, P, Grabe, H, Hamsten, A, Hui, J, Hveem, K, Jöckel, K, Kivimaki, M, Kuh, D, Laakso, M, Liu, Y, März, W, Munroe, P, Njolstad, I, Oostra, B, Pedersen, N, Perola, M, Pe'Russe, L, Peters, U, Power, C, Quertermous, T, Rauramaa, R, Rivadeneira, F, Saaristo, T, Saleheen, D, Sinisalo, J, Slagboom, P, Snieder, H, Spector, T, Thorsteinsdottir, U, Stumvoll, M, Tuomilehto, J, Uitterlinden, A, Uusitupa, M, Van Der Harst, P, Veronesi, G, Walker, M, Wareham, N, Watkins, H, Wichmann, H, Abecasis, G, Assimes, T, Berndt, S, Boehnke, M, Borecki, I, Deloukas, P, Franke, L, Frayling, T, Groop, L, Hunter, D, Kaplan, R, O'Connell, J, Qi, L, Schlessinger, D, Strachan, D, Stefansson, K, Van Duijn, C, Willer, C, Visscher, P, Yang, J, Hirschhorn, J, Zillikens, M, Mccarthy, M, Speliotes, E, North, K, Fox, C, Barroso, I, Franks, P, Ingelsson, E, Heid, I, Loos, R, Cupples, L, Lindgren, C, Mohlke, K, Dastani, Z, Timpson, N, Yuan, X, Henneman, P, Kizer, J, Lyytikainen, L, Fuchsberger, C, Small, K, Coassin, S, Lohman, K, Pankow, J, Uh, H, Wu, Y, Bidulescu, A, Rasmussen Torvik, L, Greenwood, C, Ladouceur, M, Grimsby, J, Manning, A, Mooser, V, Kapur, K, Frants, R, Willemsvan vanDijk, K, Willems, S, Psaty, B, Tracy, R, Brody, J, Chen, I, Viikari, J, Kähönen, M, Evans, D, St Pourcain, B, Sattar, N, Carlson, O, Egan, J, van Heemst, D, Kedenko, L, Nuotio, M, Loo, B, Kanaya, A, Haun, M, Klopp, N, Katsareli, E, Couper, D, Duncan, B, Kloppenburg, M, Borja, J, Musani, S, Guo, X, Semple, R, Teslovich, T, Allison, M, Redline, S, Buxbaum, S, Meulenbelt, I, Ballantyne, C, Hu, F, Paulweber, B, Florez, J, Smith, G, Siscovick, D, Kronenberg, F, van Duijn, C, Waterworth, D, Meigs, J, Dupuis, J, Richards, J, Willenborg, C, Thompson, J, Erdmann, J, Goldstein, B, König, I, Cazier, J, Johansson, Å, Hall, A, Lee, J, Grundberg, E, Havulinna, A, Ho, W, Hopewell, J, Eriksson, N, Lundmark, P, Lyytikäinen, L, Rafelt, S, Tikkanen, E, Van Zuydam, N, Voight, B, Ziegler, A, Altshuler, D, Balmforth, A, Braund, P, Burgdorf, C, Cox, D, Dimitriou, M, Do, R, El Mokhtari, N, Fontanillas, P, Hager, J, Han, B, Kang, H, Kessler, T, Knowles, J, Kolovou, G, Langford, C, Lokki, M, Lundmark, A, Meisinger, C, Melander, O, Maouche, S, Nikus, K, Peden, J, Rasheed, A, Rosinger, S, Rubin, D, Rumpf, M, Schäfer, A, Sivananthan, M, Stewart, A, Tan, S, Thorgeirsson, G, van der Schoot, C, Wagner, P, Wells, G, Wild, P, Yang, T, Basart, H, Boerwinkle, E, Brambilla, P, Cambien, F, Cupples, A, de Faire, U, Dehghan, A, Diemert, P, Epstein, S, Evans, A, Ferrario, M, Gauguier, D, Goodall, A, Hazen, S, Holm, H, Iribarren, C, Jang, Y, Kim, H, Laaksonen, R, Ouwehand, W, Parish, S, Park, J, Rader, D, Shah, S, Stark, K, Trégouët, D, Virtamo, J, Wallentin, L, Zimmermann, M, Nieminen, M, Hengstenberg, C, Sandhu, M, Pastinen, T, Hovingh, G, Zalloua, P, Siegbahn, A, Schreiber, S, Ripatti, S, Blankenberg, S, O'Donnell, C, Reilly, M, Collins, R, Kathiresan, S, Roberts, R, Schunkert, H, Pattaro, C, Köttgen, A, Garnaas, M, Böger, C, Chen, M, Tin, A, Taliun, D, Li, M, Gao, X, Gorski, M, Yang, Q, Hundertmark, C, Foster, M, O'Seaghdha, C, Glazer, N, Struchalin, M, Li, G, Johnson, A, Gierman, H, Hwang, S, Atkinson, E, Cornelis, M, Chouraki, V, Holliday, E, Sorice, R, Deshmukh, H, Ulivi, S, Chu, A, Murgia, F, Trompet, S, Imboden, M, Kollerits, B, Pistis, G, Launer, L, Aspelund, T, Eiriksdottir, G, Mitchell, B, Schmidt, H, Cavalieri, M, Rao, M, de Andrade, M, Turner, S, Ding, J, Andrews, J, Freedman, B, Döring, A, Kolcic, I, Zemunik, T, Boban, M, Minelli, C, Wheeler, H, Igl, W, Zaboli, G, Wild, S, Wright, A, Ellinghaus, D, Nöthlings, U, Jacobs, G, Biffar, R, Endlich, K, Ernst, F, Kroemer, H, Nauck, M, Stracke, S, Völzke, H, Aulchenko, Y, Polasek, O, Hastie, N, Vitart, V, Helmer, C, Wang, J, Ruggiero, D, Bergmann, S, Nikopensius, T, Province, M, Ketkar, S, Colhoun, H, Robino, A, Giulianini, F, Krämer, B, Portas, L, Ford, I, Buckley, B, Adam, M, Thun, G, Sala, C, Metzger, M, Mitchell, P, Ciullo, M, Kim, S, Gasparini, P, Pirastu, M, Jukema, J, Probst Hensch, N, Toniolo, D, Coresh, J, Schmidt, R, Kardia, S, Curhan, G, Gyllensten, U, Franke, A, Rettig, R, Parsa, A, Goessling, W, Kao, W, de Boer, I, Peralta, C, Akylbekova, E, Kramer, H, van der Harst, P, Arking, D, Franceschini, N, Hernandez, D, Townsend, R, Lumley, T, Kestenbaum, B, Haritunians, T, Waeber, G, Lu, X, Leak, T, Aasarød, K, Skorpen, F, Baumert, J, Devuyst, O, Mychaleckyj, J, Hallan, S, Navis, G, Shlipak, M, Bull, S, Paterson, A, Rotter, J, Beckmann, J, Dreisbach, A, Styrkarsdottir, U, Evangelou, E, Hsu, Y, Duncan, E, Ntzani, E, Oei, L, Albagha, O, Kemp, J, Koller, D, Minster, R, Vandenput, L, Willner, D, Xiao, S, Yerges Armstrong, L, Zheng, H, Alonso, N, Kammerer, C, Kaptoge, S, Leo, P, Wilson, S, Aalto, V, Alen, M, Aragaki, A, Center, J, Dailiana, Z, Duggan, D, Garcia Giralt, N, Giroux, S, Hocking, L, Husted, L, Jameson, K, Khusainova, R, Kim, G, Koromila, T, Kruk, M, Laaksonen, M, Lacroix, A, Lee, S, Leung, P, Lewis, J, Masi, L, Mencej Bedrac, S, Nguyen, T, Nogues, X, Patel, M, Prezelj, J, Scollen, S, Siggeirsdottir, K, Svensson, O, Trummer, O, van Schoor, N, Woo, J, Zhu, K, Balcells, S, Brandi, M, Cheng, S, Christiansen, C, Cooper, C, Frost, M, Goltzman, D, González Macías, J, Karlsson, M, Khusnutdinova, E, Koh, J, Kollia, P, Langdahl, B, Leslie, W, Lips, P, Ljunggren, Ö, Lorenc, R, Marc, J, Mellström, D, Obermayer Pietsch, B, Olmos, J, Pettersson Kymmer, U, Reid, D, Riancho, J, Rousseau, F, Tang, N, Urreizti, R, Van Hul, W, Zarrabeitia, M, Castano Betancourt, M, Herrera, L, Ingvarsson, T, Johannsdottir, H, Kwan, T, Li, R, Luben, R, Medina Gómez, C, Palsson, S, Reppe, S, Sigurdsson, G, van Meurs, J, Verlaan, D, Williams, F, Zhou, Y, Gautvik, K, Raychaudhuri, S, Cauley, J, Clark, G, Cummings, S, Danoy, P, Dennison, E, Eastell, R, Eisman, J, Jackson, R, Jones, G, Khaw, K, Mccloskey, E, Nandakumar, K, Peacock, M, Pols, H, Prince, R, Reid, I, Robbins, J, Sambrook, P, Sham, P, Tylavsky, F, Econs, M, Kung, A, Reeve, J, Streeten, E, Karasik, D, Ralston, S, Ioannidis, J, Kiel, D, Forsblom, C, Isakova, T, Mckay, G, Williams, W, Sadlier, D, Mäkinen, V, Swan, E, Boright, A, Ahlqvist, E, Keller, B, Huang, H, Ahola, A, Fagerholm, E, Gordin, D, Harjutsalo, V, He, B, Heikkilä, O, Hietala, K, Kytö, J, Lahermo, P, Lehto, M, Österholm, A, Parkkonen, M, Pitkäniemi, J, Rosengård Bärlund, M, Saraheimo, M, Sarti, C, Söderlund, J, Soro Paavonen, A, Syreeni, A, Thorn, L, Tikkanen, H, Tolonen, N, Tryggvason, K, Wadén, J, Gill, G, Prior, S, Guiducci, C, Mirel, D, Taylor, A, Hosseini, M, Parving, H, Rossing, P, Tarnow, L, Ladenvall, C, Alhenc Gelas, F, Lefebvre, P, Rigalleau, V, Roussel, R, Tregouet, D, Maestroni, A, Maestroni, S, Falhammar, H, Gu, T, Möllsten, A, Cimponeriu, D, Mihai, I, Mota, M, Mota, E, Serafinceanu, C, Stavarachi, M, Hanson, R, Nelson, R, Kretzler, M, Panduru, N, Gu, H, Brismar, K, Zerbini, G, Hadjadj, S, Marre, M, Lajer, M, Waggott, D, Savage, D, Bain, S, Martin, F, Godson, C, Groop, P, Maxwell, A, Sengupta, S, Peloso, G, Ganna, A, Mora, S, Chang, H, Den Hertog, H, Donnelly, L, Fraser, R, Freitag, D, Gurdasani, D, Kaakinen, M, Kettunen, J, Li, X, Montasser, M, Petersen, A, Saxena, R, Service, S, Sidore, C, Surakka, I, Van den Herik, E, Volcik, K, Asiki, G, Been, L, Bolton, J, Bonnycastle, L, Burnett, M, Cesana, G, Elliott, P, Eyjolfsson, G, Goodarzi, M, Gravito, M, Hartikainen, A, Hung, Y, Jones, M, Kaleebu, P, Kastelein, J, Kim, E, Komulainen, P, Lin, S, Nieminen, T, Nsubuga, R, Olafsson, I, Palotie, A, Papamarkou, T, Pomilla, C, Pouta, A, Ruokonen, A, Seeley, J, Silander, K, Stančáková, A, Tiret, L, van Pelt, L, Wainwright, N, Wijmenga, C, Willemsen, G, Young, E, Bennett, F, Boomsma, D, Bovet, P, Chen, Y, Feranil, A, Freimer, N, Hsiung, C, Järvelin, M, Kesäniemi, A, Koudstaal, P, Krauss, R, Kyvik, K, Martin, N, Meneton, P, Moilanen, L, Njølstad, I, Price, J, Sanghera, D, Sheu, W, Whitfield, J, Wolffenbuttel, B, Ordovas, J, Rich, S, Johnson, L, Larson, M, Levy, D, Newton Cheh, C, O'Reilly, P, Palmas, W, Rice, K, Snider, H, Tobin, M, Verwoert, G, Pihur, V, Heath, S, Sõber, S, Arora, P, Zhang, F, Lucas, G, Milaneschi, Y, Parker, A, Fava, C, Fox, E, Go, M, Sjögren, M, Vinay, D, Alexander, M, Tabara, Y, Shaw Hawkins, S, Whincup, P, Shi, G, Seielstad, M, Sim, X, Nguyen, K, Matullo, G, Gaunt, T, Onland Moret, N, Cooper, M, Platou, C, Org, E, Hardy, R, Dahgam, S, Palmen, J, Kuznetsova, T, Uiterwaal, C, Adeyemo, A, Ludwig, B, Tomaszewski, M, Tzoulaki, I, Palmer, N, Chang, Y, Steinle, N, Grobbee, D, Morrison, A, Najjar, S, Hadley, D, Connell, J, Day, I, Lawlor, D, Lawrence, R, Ongen, H, Li, Y, Young, J, Bis, J, Chaturvedi, N, Islam, M, Jafar, T, Kulkarni, S, Grässler, J, Howard, P, Guarrera, S, Ricceri, F, Emilsson, V, Plump, A, Weder, A, Sun, Y, Scott, L, Peltonen, L, Vartiainen, E, Brand, S, Wang, T, Burton, P, Artigas, M, Dong, Y, Wang, X, Zhu, H, Rudock, M, Heckbert, S, Smith, N, Wiggins, K, Doumatey, A, Shriner, D, Veldre, G, Viigimaa, M, Kinra, S, Prabhakaran, D, Tripathy, V, Langefeld, C, Rosengren, A, Thelle, D, Corsi, A, Singleton, A, Hilton, G, Salako, T, Iwai, N, Kita, Y, Ogihara, T, Ohkubo, T, Okamura, T, Ueshima, H, Umemura, S, Eyheramendy, S, Meitinger, T, Cho, Y, Scott, J, Sehmi, J, Hedblad, B, Nilsson, P, Stanèáková, A, Raffel, L, Yao, J, Schwartz, S, Ikram, M, Longstreth W., J, Mosley, T, Seshadri, S, Shrine, N, Wain, L, Morken, M, Laitinen, J, Zitting, P, Cooper, J, van Gilst, W, Janipalli, C, Mani, K, Yajnik, C, Mattace Raso, F, Lakatta, E, Orru, M, Scuteri, A, Ala Korpela, M, Kangas, A, Soininen, P, Tukiainen, T, Würtz, P, Ong, R, Galan, P, Hercberg, S, Lathrop, M, Zelenika, D, Zhai, G, Meschia, J, Sharma, P, Terzic, J, Kumar, M, Denniff, M, Zukowska Szczechowska, E, Wagenknecht, L, Fowkes, F, Charchar, F, Rotimi, C, Bots, M, Brand, E, Talmud, P, Nyberg, F, Laan, M, van der Schouw, Y, Casas, J, Vineis, P, Ganesh, S, Wong, T, Tai, E, Morris, R, Dominiczak, A, Marmot, M, Miki, T, Chandak, G, Zhu, X, Elosua, R, Soranzo, N, Sijbrands, E, Uda, M, Vasan, R, Anderson, C, Gordon, S, Guo, Q, Henders, A, Lambert, A, Kraft, P, Kennedy, S, Macgregor, S, Missmer, S, Painter, J, Roseman, F, Treloar, S, Wallace, L, Alizadeh, B, de Boer, R, Boezen, H, van der Klauw, M, Ormel, J, Postma, D, Rosmalen, J, Slaets, J, Lagou, V, Welch, R, Wheeler, E, Rehnberg, E, Lecoeur, C, Johnson, P, Hottenga, J, Salo, P, Bielak, L, Zhao, W, Horikoshi, M, Navarro, P, Chen, H, Rybin, D, Song, K, An, P, Marullo, L, Jansen, H, Edkins, S, Varga, T, Oksa, H, Antonella, M, Kong, A, Herder, C, Antti, J, Miljkovic, I, Atalay, M, Kiess, W, Smit, J, Campbell, S, Fowkes, G, Rathmann, W, Maerz, W, Watanabe, R, de Geus, E, Toenjes, A, Peyser, P, Körner, A, Cucca, F, Balkau, B, Bouatia Naji, N, Ahmadi, K, Ainali, C, Bataille, V, Bell, J, Buil, A, Dermitzakis, E, Dimas, A, Durbin, R, Glass, D, Hassanali, N, Hedman, Å, Ingle, C, Knowles, D, Krestyaninova, M, Lowe, C, Meduri, E, di Meglio, P, Montgomery, S, Nestle, F, Nica, A, Nisbet, J, O'Rahilly, S, Parts, L, Potter, S, Sekowska, M, Shin, S, Surdulescu, G, Travers, M, Tsaprouni, L, Tsoka, S, Wilk, A, Higashio, J, Williams, R, Nato, A, Ambite, J, Manolio, T, Hindorff, L, Heiss, G, Taylor, K, Avery, C, Graff, M, Lin, D, Quibrera, M, Cochran, B, Kao, L, Umans, J, Cole, S, Maccluer, J, Person, S, Gross, M, Fornage, M, Durda, P, Jenny, N, Patsy, B, Arnold, A, Buzkova, P, Haines, J, Murdock, D, Glenn, K, Brown Gentry, K, Thornton Wells, T, Dumitrescu, L, Jeff, J, Bush, W, Mitchell, S, Goodloe, R, Boston, J, Malinowski, J, Restrepo, N, Oetjens, M, Fowke, J, Zheng, W, Spencer, K, Pendergrass, S, Wilkens, L, Park, L, Tiirikainen, M, Kolonel, L, Lim, U, Cheng, I, Wang, H, Shohet, R, Stram, D, Henderson, B, Monroe, K, Schumacher, F, Anderson, G, Carlson, C, Prentice, R, Wu, C, Carty, C, Gong, J, Rosse, S, Young, A, Haessler, J, Kocarnik, J, Lin, Y, Kuller, L, He, C, Sulem, P, Barbalic, M, Broer, L, Byrne, E, Gudbjartsson, D, Mcardle, P, Porcu, E, van Wingerden, S, Zhuang, W, Lauc, L, Broekmans, F, Burri, A, Chanock, S, Chen, C, Corre, T, Coviello, A, D'Adamo, P, Davies, G, Deary, I, Ebrahim, S, Fauser, B, Ferreli, L, Folsom, A, Hall, P, Hankinson, S, Hass, M, Heath, A, Janssens, A, Keyzer, J, Lahti, J, Lai, S, Laisk, T, Laven, J, Liu, J, Lopez, L, Louwers, Y, Marongiu, M, Klaric, I, Masciullo, C, Medland, S, Melzer, D, Newman, A, Paré, G, Peeters, P, Pop, V, Räikkönen, K, Salumets, A, Smith, J, Stacey, S, Starr, J, Stathopoulou, M, Tenesa, A, Tryggvadottir, L, Tsui, K, van Dam, R, van Gils, C, van Nierop, P, Vink, J, Voorhuis, M, Wallaschofski, H, Widen, E, Wijnands van Gent, C, Zgaga, L, Zygmunt, M, Buring, J, Crisponi, L, Demerath, E, Murray, A, Visser, J, Lunetta, K, Elks, C, Cousminer, D, Feenstra, B, Lin, P, Smith, E, Warrington, N, Alavere, H, Berenson, G, Blackburn, H, Busonero, F, Chen, W, Easton, D, Foroud, T, Geller, F, Kilpeläinen, T, Li, S, Melbye, M, Murray, J, Murray, S, Ness, A, Northstone, K, Pennell, C, Pharoah, P, Rafnar, T, Rice, J, Ring, S, Schork, N, Segrè, A, Sovio, U, Srinivasan, S, Tammesoo, M, Tyrer, J, Weedon, M, Young, L, Bierut, L, Boyd, H, Psychiatry, NCA - Neurobiology of mental health, and EMGO - Lifestyle, overweight and diabetes
Subjects: Adipose Tissue/metabolism, Male, genetic association, subcutaneous fat, Transcription, Genetic, Adipocytes, Adipogenesis, Adipose Tissue, Age Factors, Body Mass Index, Continental Population Groups, Epigenesis, Genetic, Europe, Female, Genome, Human, Humans, Insulin, Insulin Resistance, Models, Biological, Neovascularization, Physiologic, Obesity, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Sex Characteristics, Waist-Hip Ratio, Body Fat Distribution, Genome-Wide Association Study, Multidisciplinary, Insulin Resistance/genetics, Genome-wide association study, Continental Population Groups/genetics, genetic analysis, heritability, gene cluster, Science::Biological sciences::Human anatomy and physiology [DRNTU], 0302 clinical medicine, high density lipoprotein cholesterol, Models, genetics [Insulin Resistance], histone modification, Age Factor, insulin receptor, 0303 health sciences, Adipocyte, Human/genetics, CARDIOGRAMplusC4D Consortium, ADIPOGENIC DIFFERENTIATION, genetic correlation, body fat, Continental Population Group, priority journal, 5 trisphosphate 3 phosphatase, GEFOS Consortium, meta analysis (topic), Science & Technology - Other Topics, ddc:500, transcription regulation, Adipogenesis/genetics, Single Nucleotide/genetics, Human, medicine.medical_specialty, Waist, phosphatidylinositol 3, European, ta3111, genetic regulation, Article, developmental biology, 03 medical and health sciences, MAGIC Investigators, transcription initiation site, SDG 3 - Good Health and Well-being, Genetic, genomics, GLYCEMIC TRAITS, genetics [Continental Population Groups], Polymorphism, GENOME-WIDE ASSOCIATION, Physiologic, genetics [Adipogenesis], Adipocytes/metabolism, Europe/ethnology, Genome, Human/genetics, Insulin/metabolism, Neovascularization, Physiologic/genetics, Obesity/genetics, Polymorphism, Single Nucleotide/genetics, Quantitative Trait Loci/genetics, Transcription, Genetic/genetics, Genetic/genetics, Adipogenesi, Science & Technology, adiponectin, [ SDV ] Life Sciences [q-bio], vasculotropin, genetics [Quantitative Trait Loci], ta1184, Racial Groups, ta1182, gene mapping, ta3121, triacylglycerol blood level, medicine.disease, Biological, major clinical study, amino acid sequence, metabolism [Insulin], Endocrinology, metabolism [Adipocytes], genetic loci, insulin, body fat, GLGC, International Endogene Consortium, metabolism [Adipose Tissue], Body mass index, HUMAN HEIGHT, Epigenesis, LifeLines Cohort Study, ReproGen Consortium, BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, tissue level, Physiologic/genetics, [SDV]Life Sciences [q-bio], Medizin, Adipose tissue, low density lipoprotein cholesterol, PAGE Consortium, COMMON SNPS, angiogenesis, Waist–hip ratio, genetics [Obesity], MESH: Adipocytes/metabolism Adipogenesis/genetics Adipose Tissue/metabolism* Age Factors Body Fat Distribution* Body Mass Index Continental Population Groups/genetics Epigenesis, Genetic Europe/ethnology Female Genome, Human/genetics Genome-Wide Association Study* Humans Insulin/metabolism* Insulin Resistance/genetics Male Models, Biological Neovascularization, Physiologic/genetics Obesity/genetics Polymorphism, Single Nucleotide/genetics Quantitative Trait Loci/genetics* Sex Characteristics Transcription, Genetic/genetics Waist-Hip Ratio, single nucleotide polymorphism, fat, genetic variability, molecular biology, body mass index (BMI), ethnology [Europe], peroxisome proliferator activated receptor, 2. Zero hunger, Genetics, Genome, Single Nucleotide, waist circumference, insulin, phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase, triacylglycerol, vasculotropin, developmental biology, gene expression, genome, numerical model, adipocyte, adipose tissue, body fat distribution, body mass, female, gene locus, gene structure, hip circumference, human, insulin resistance, lipoprotein blood level, male, obesity, protein protein interaction, sex difference, waist hip ratio, Multidisciplinary Sciences, genetics [Transcription, Genetic], genetics [Polymorphism, Single Nucleotide], ADIPOGen Consortium, genetics [Neovascularization, Physiologic], Transcription, SUSCEPTIBILITY LOCI, General Science & Technology, ICBP, 030209 endocrinology & metabolism, Biology, adipocyte, MESH : Adipocytes/metabolism Adipogenesis/genetics Adipose Tissue/metabolism* Age Factors Body Fat Distribution* Body Mass Index Continental Population Groups/genetics Epigenesis, Genetic Europe/ethnology Female Genome, Human/genetics Genome-Wide Association Study* Humans Insulin/metabolism* Insulin Resistance/genetics Male Models, Biological Neovascularization, Physiologic/genetics Obesity/genetics Polymorphism, Single Nucleotide/genetics Quantitative Trait Loci/genetics* Sex Characteristics Transcription, Genetic/genetics Waist-Hip Ratio, MESENCHYMAL STEM-CELLS, GENIE Consortium, SEXUAL-DIMORPHISM, Insulin resistance, Internal medicine, medicine, genetics [Genome, Human], ABDOMINAL ADIPOSITY, Neovascularization, 030304 developmental biology, FALSE DISCOVERY, CKDGen Consortium, Sex Characteristic, MuTHER Consortium, numerical model
Abstract: Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P
Published: 2015

16. Safety of intravitreal chemotherapy in the management of retinoblastoma: A systematic review of the literature.

Author: Lavasidis G, Strongylis M, Tzamalis A, Tsinopoulos I, and Ntzani EE
Subjects: Humans, Antineoplastic Agents adverse effects, Antineoplastic Agents administration & dosage, Antineoplastic Agents therapeutic use, Intravitreal Injections, Retinal Neoplasms drug therapy, Retinal Neoplasms pathology, Retinoblastoma drug therapy, Retinoblastoma pathology
Abstract: Intravitreal chemotherapy is used as a salvage therapy for retinoblastoma with persistent or recurrent vitreous seeding after primary treatment. To assess the safety of this technique, we conducted a systematic review of all studies reporting ocular toxicity data. Forty-eight trials involving 2751 eyes were included. The most common complications were cataract, retinal toxicity, and vitreous hemorrhage. However, severe and permanent adverse events were limited, while the risk of extraocular dissemination, a significant concern, was practically eliminated through preventive techniques. Globe salvage rates ranged from 29 % to 100 %. In conclusion, intravitreal chemotherapy seems to improve prognosis of eyes with advanced disease, with an acceptable safety profile. Nevertheless, most relevant studies are retrospective, and no randomized trials have been performed. Recognizing the challenges regarding the conduct of randomized studies for such a rare pediatric cancer, we believe that multicenter trials through international collaborations can significantly enhance the available information., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)
Published: 2024
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17. Unravelling Beau's Lines as a Potential Indicator of Severe Immune Response in Covid-19 and Reinfection.

Author: Agouridis AP, Ntzani EE, Anastasiou G, Barkas F, and Rizos EC
Abstract: Background: Beau's lines are transverse grooves in the nail plate that result from transient interruption of the growth of the proximal nail matrix. These rare nail disorders can be triggered mostly by infections or systemic diseases., Case Description: We describe a 65-year-old man who presented with nail changes on all fingernails. The patient, a non-smoker with no medication history, had severe immune responses during two hospitalisations, 9 and 4 months ago, for COVID-19. Both hospitalisations were accompanied by markedly elevated interleukin-6 levels, and treatment with tocilizumab on top of dexamethasone was required. The present examination revealed Beau's lines which were associated with both prior COVID-19 infections., Conclusions: Although nail changes look harmless, seeking Beau's lines during the physical examination might indicate past severe COVID-19 infection and a higher probability for reinfection and rehospitalisation., Learning Points: Beau's lines are grooves that traverse the nail plate horizontally.The appearance of Beau's lines may indicate past severe COVID-19 infection.Beau's lines can potentially indicate a higher probability of COVID-19 reinfection and rehospitalisation., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests., (© EFIM 2024.)
Published: 2024
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18. Supportive interventions for childhood cancer: An umbrella review of randomized evidence.

Author: Lavasidis G, Markozannes G, Voorhies K, Trikalinos NA, Petridou ET, Panagiotou OA, and Ntzani EE
Subjects: Child, Humans, Nausea, Quality of Life, Survivors, Vomiting, Randomized Controlled Trials as Topic, Neoplasms drug therapy
Abstract: Therapeutic advancements have improved pediatric cancer prognosis, shifting the interest towards the management of psychosocial burden and treatment-related morbidity. To critically appraise the available evidence, we conducted an umbrella review of meta-analyses of randomized controlled trials on supportive interventions for childhood cancer. Thirty-four publications (92 meta-analyses, 1 network, 14,521 participants) were included. The most concrete data showed a reduction in procedure-related pain and distress through hypnosis. Moreover, exercise improved the functional mobility of the patients. Regarding pharmacological interventions, most of the meta-analyses pertained to the treatment of nausea/vomiting (ondansetron was effective) and infections/febrile neutropenia [granulocyte-(macrophage) colony-stimulating factors showed benefits]. Substantial heterogeneity was detected in 31 associations. Conclusively, supportive interventions for pediatric cancer are being thoroughly evaluated. However, most of the studies are small and of moderate quality, highlighting the need for more randomized evidence in order to increase precision in improving the quality of life of patients, survivors and their families., Competing Interests: Conflict of interest Dr. Panagiotou reports personal fees from International Consulting Associates, Inc. outside the scope of the submitted work. Dr. Trikalinos is the PI for pharmaceutical sponsored trials at his institution. None includes the interventions or population addressed in our paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)
Published: 2022
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19. Nutritional Status at Diagnosis as Predictor of Survival from Childhood Cancer: A Review of the Literature.

Author: Karalexi MA, Markozannes G, Tagkas CF, Katsimpris A, Tseretopoulou X, Tsilidis KK, Spector LG, Schüz J, Siahanidou T, Petridou ET, and Ntzani EE
Abstract: Few studies so far have examined the impact of nutritional status on the survival of children with cancer, with the majority of them focusing on hematological malignancies. We summarized published evidence reporting the association of nutritional status at diagnosis with overall survival (OS), event-free survival (EFS), relapse, and treatment-related toxicity (TRT) in children with cancer. Published studies on children with leukemia, lymphoma, and other solid tumors have shown that both under-nourished and over-nourished children at cancer diagnosis had worse OS and EFS. Particularly, the risk of death and relapse increased by 30-50% among children with leukemia with increased body mass index at diagnosis. Likewise, the risk of TRT was higher among malnourished children with osteosarcoma and Ewing sarcoma. Nutritional status seems to play a crucial role in clinical outcomes of children with cancer, thus providing a significant modifiable prognostic tool in childhood cancer management. Future studies with adequate power and longitudinal design are needed to further evaluate the association of nutritional status with childhood cancer outcomes using a more standardized definition to measure nutritional status in this population. The use of new technologies is expected to shed further light on this understudied area and give room to person-targeted intervention strategies.
Published: 2022
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20. SARS-CoV-2 Sero-Surveillance in Greece: Evolution over Time and Epidemiological Attributes during the Pre-Vaccination Pandemic Era.

Author: Koureas M, Bogogiannidou Z, Vontas A, Kyritsi MA, Mouchtouri VA, Dadouli K, Anagnostopoulos L, Mina P, Matziri A, Ntouska M, Tsigaridaki M, Gkiata V, Tsilidis KK, Ntzani EE, Prezerakos P, Tsiodras S, Speletas M, and Hadjichristodoulou C
Abstract: Background: Nation-wide SARS-CoV-2 seroprevalence surveys provide valuable insights into the course of the pandemic, including information often not captured by routine surveillance of reported cases., Methods: A serosurvey of IgG antibodies against SARS-CoV-2 was conducted in Greece between March and December 2020. It was designed as a cross-sectional survey repeated at monthly intervals. The leftover sampling methodology was used and a geographically stratified sampling plan was applied., Results: Of 55,947 serum samples collected, 705 (1.26%) were found positive for anti-SARS-CoV-2 antibodies, with higher seroprevalence (9.09%) observed in December 2020. Highest seropositivity levels were observed in the "0-29" and "30-49" year age groups. Seroprevalence increased with age in the "0-29" age group. Highly populated metropolitan areas were characterized with elevated seroprevalence levels (11.92% in Attica, 12.76% in Thessaloniki) compared to the rest of the country (5.90%). The infection fatality rate (IFR) was estimated at 0.451% (95% CI: 0.382-0.549%) using aggregate data until December 2020, and the ratio of actual to reported cases was 9.59 (7.88-11.33)., Conclusions: The evolution of seroprevalence estimates aligned with the course of the pandemic and varied widely by region and age group. Young and middle-aged adults appeared to be drivers of the pandemic during a severe epidemic wave under strict policy measures.
Published: 2022
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21. Factors Associated with Healthcare Workers' (HCWs) Acceptance of COVID-19 Vaccinations and Indications of a Role Model towards Population Vaccinations from a Cross-Sectional Survey in Greece, May 2021.

Author: Fotiadis K, Dadouli K, Avakian I, Bogogiannidou Z, Mouchtouri VA, Gogosis K, Speletas M, Koureas M, Lagoudaki E, Kokkini S, Bolikas E, Diamantopoulos V, Tzimitreas A, Papadopoulos C, Farmaki E, Sofos A, Chini M, Tsolia M, Papaevangelou V, Ntzani EE, Gikas A, Prezerakos P, and Hadjichristodoulou C
Subjects: Cross-Sectional Studies, Greece, Health Knowledge, Attitudes, Practice, Health Personnel, Humans, SARS-CoV-2, Surveys and Questionnaires, Vaccination, COVID-19, COVID-19 Vaccines
Abstract: A Knowledge, Attitudes and Practices (KAP) study was conducted at the end of May 2021 engaging 1456 healthcare workers (HCWs) from 20 hospitals throughout Greece. Acceptance of vaccination against coronavirus disease 2019 (COVID-19) was estimated at 77.7%, with lower vaccine acceptance identified in nurses compared to physicians. Fears related to vaccine safety, lack of information and general knowledge about vaccinations, influenza vaccine acceptance, education level and years of practice were among the factors independently associated with vaccine acceptance. A strong association was identified between vaccination of HCWs in each health region and the population coverage, indicating that HCWs may be role models for the general population. Information campaigns should continue despite decisions taken regarding mandatory vaccinations.
Published: 2021
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22. High-density lipoprotein cholesterol: A marker of COVID-19 infection severity?

Author: Agouridis AP, Pagkali A, Zintzaras E, Rizos EC, and Ntzani EE
Abstract: Background and Aims: To systematically address all the relevant evidence of the association between high-density lipoprotein cholesterol (HDL-C) and COVID-19 infection., Methods: We searched PubMed, PubMed Central and medRxiv databases (up to May 2021) for studies related to HDL-C and COVID-19 infection. A qualitative synthesis of published prospective and retrospective studies for the role of low HDL-C levels on COVID-19 infection severity was performed., Results: Thirty-three studies (6 prospective, 27 retrospective) including 11,918 COVID-19 patients were eligible for the systematic review. Twelve studies compared HDL-C levels on admission in COVID-19 patients with healthy controls. In these 12 studies, COVID-19 patients had significantly lower HDL-C levels on admission compared with that of healthy controls. Twenty-eight studies observed the HDL-C levels among COVID-19 diagnosed patients, to establish the role of low HDL-C values in the prognosis of the infection. Twenty-four studies showed a correlation between low HDL-C levels with disease severity, while only 4 studies showed no association., Conclusions: Low HDL-C levels should be added in the list of the others well-known risk factors for COVID-19 severity., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors.)
Published: 2021
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23. Exposure to pesticides and childhood leukemia risk: A systematic review and meta-analysis.

Author: Karalexi MA, Tagkas CF, Markozannes G, Tseretopoulou X, Hernández AF, Schüz J, Halldorsson TI, Psaltopoulou T, Petridou ET, Tzoulaki I, and Ntzani EE
Subjects: Case-Control Studies, Environmental Exposure, Female, Humans, Infant, Male, Maternal Exposure, Paternal Exposure, Pregnancy, Risk Factors, Occupational Exposure, Pesticides, Precursor Cell Lymphoblastic Leukemia-Lymphoma chemically induced, Precursor Cell Lymphoblastic Leukemia-Lymphoma epidemiology, Prenatal Exposure Delayed Effects epidemiology
Abstract: Despite the abundance of epidemiological evidence concerning the association between pesticide exposure and adverse health outcomes including acute childhood leukemia (AL), evidence remains inconclusive, and is inherently limited by heterogeneous exposure assessment and multiple statistical testing. We performed a literature search of peer-reviewed studies, published until January 2021, without language restrictions. Summary odds ratios (OR) and 95% confidence intervals (CI) were derived from stratified random-effects meta-analyses by type of exposure and outcome, exposed populations and window of exposure to address the large heterogeneity of existing literature. Heterogeneity and small-study effects were also assessed. We identified 55 eligible studies (n = 48 case-control and n = 7 cohorts) from over 30 countries assessing >200 different exposures of pesticides (n = 160,924 participants). The summary OR for maternal environmental exposure to pesticides (broad term) during pregnancy and AL was 1.88 (95%CI: 1.15-3.08), reaching 2.51 for acute lymphoblastic leukemia (ALL; 95%CI: 1.39-4.55). Analysis by pesticide subtype yielded an increased risk for maternal herbicide (OR: 1.41, 95%CI: 1.00-1.99) and insecticide (OR: 1.60, 95%CI: 1.11-2.29) exposure during pregnancy and AL without heterogeneity (p = 0.12-0.34). Meta-analyses of infant leukemia were only feasible for maternal exposure to pesticides during pregnancy. Higher magnitude risks were observed for maternal pesticide exposure and infant ALL (OR: 2.18, 95%CI: 1.44-3.29), and the highest for infant acute myeloid leukemia (OR: 3.42, 95%CI: 1.98-5.91). Overall, the associations were stronger for maternal exposure during pregnancy compared to childhood exposure. For occupational or mixed exposures, parental, and specifically paternal, pesticide exposure was significantly associated with increased risk of AL (OR parental : 1.75, 95%CI: 1.08-2.85; OR paternal : 1.20, 95%CI: 1.07-1.35). The epidemiological evidence, supported by mechanistic studies, suggests that pesticide exposure, mainly during pregnancy, increases the risk of childhood leukemia, particularly among infants. Sufficiently powered studies using repeated biomarker analyses are needed to confirm whether there is public health merit in reducing prenatal pesticide exposure., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
Published: 2021
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24. Therapeutic interventions for childhood cancer: An umbrella review of randomized evidence.

Author: Lavasidis G, Markozannes G, Panagiotou OA, Trikalinos NA, Petridou ET, Voorhies K, and Ntzani EE
Subjects: Adult, Child, Humans, Randomized Controlled Trials as Topic, Neoplasms drug therapy
Abstract: Treatment advancements in pediatric cancer have improved prognosis, but the strength of supporting evidence has not been thoroughly evaluated. To critically appraise it, we performed an umbrella review of meta-analyses of randomized controlled trials examining the efficacy and safety of therapeutic interventions for pediatric malignancies. Fourteen publications (68 meta-analyses, 31,496 participants) were eligible. Acute lymphoblastic leukemia (ALL) was investigated at most. Substantial heterogeneity was detected in 10 associations, with limited indications for small-study effects and excess-significance bias. The most concrete evidence pertained to the use of methotrexate and vincristine-prednisone pulses for ALL, improving event-free survival. Evidence regarding other cancers was relatively weak. Conclusively, we found few small meta-analyses focusing mainly on ALL. Randomized evidence stemming from adult populations still seems to serve as valuable indirect evidence backup. More randomized evidence and individual patient data meta-analyses are needed to increase certainty and precision in the care of pediatric cancer patients., (Copyright © 2021 Elsevier B.V. All rights reserved.)
Published: 2021
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25. Repeated Leftover Serosurvey of SARS-CoV-2 IgG Antibodies in Greece, May to August 2020.

Author: Bogogiannidou Z, Speletas M, Vontas A, Nikoulis DJ, Dadouli K, Kyritsi MA, Mouchtouri VA, Mina P, Anagnostopoulos L, Koureas M, Karavasilis V, Nikou O, Pinaka O, Thomaidis PC, Kadoglou K, Bedevis K, Spyrou N, Eleftheriou AA, Papaevangelou V, Gikas A, Vatopoulos A, Ntzani EE, Prezerakos P, Tsiodras S, and Hadjichristodoulou C
Abstract: A serosurvey of IgG antibodies against SARS-CoV-2 was conducted in Greece between May and August 2020. It was designed as a cross-sectional survey and was repeated at monthly intervals. The leftover sampling methodology was used and a geographically stratified sampling plan was applied. Of 20,110 serum samples collected, 89 (0.44%) were found to be positive for anti-SARS-CoV-2 antibodies, with higher seroprevalence (0.35%) observed in May 2020. The highest seroprevalence was primarily observed in the "30-49" year age group. Females presented higher seroprevalence compared to males in May 2020 (females: 0.58% VS males: 0.10%). This difference reversed during the study period and males presented a higher proportion in August 2020 (females: 0.12% VS males: 0.58%). Differences in the rate of seropositivity between urban areas and the rest of the country were also observed during the study period. The four-month infection fatality rate (IFR) was estimated to be 0.47%, while the respective case fatality rate (CFR) was at 1.89%. Our findings confirm low seroprevalence of COVID-19 in Greece during the study period. The young adults are presented as the most affected age group. The loss of the cumulative effect of seropositivity in a proportion of previous SARS-CoV-2 infections was indicated.
Published: 2021
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26. Social support, adherence to Mediterranean diet and physical activity in adults: results from a community-based cross-sectional study.

Author: Laiou E, Rapti I, Markozannes G, Cianferotti L, Fleig L, Warner LM, Ribas L, Ngo J, Salvatore S, Trichopoulou A, Vigilanza A, Tsiara S, Martimianaki G, Pampaloni B, Majem LS, Schwarzer R, Brandi ML, and Ntzani EE
Subjects: Adolescent, Adult, Aged, Cross-Sectional Studies, Feeding Behavior, Female, Greece, Humans, Italy, Male, Middle Aged, Spain, Surveys and Questionnaires, Young Adult, Diet, Mediterranean, Exercise, Obesity prevention & control, Social Support
Abstract: There is a growing recognition that social support can potentially exert consistent or opposing effects in influencing health behaviours. The present paper presents a cross-sectional study, including 2,064 adults from Italy, Spain and Greece, who were participants in a multi-centre randomised controlled trial (C4H study), aiming to examine whether social support is correlated with adherence to a healthy Mediterranean diet and physical activity. Social support data were available for 1,572 participants. The majority of the sample reported emotional support availability (84·5 %), financial support availability (72·6 %) and having one or more close friends (78·2 %). Mediterranean diet adherence was significantly associated with emotional support ( P = 0·009) and social network support ( P = 0·021). No statistically significant associations were found between participant physical activity and the social support aspects studied. In conclusion, emotional and social network support may be associated with increased adherence to the Mediterranean diet. However, further research is needed to evaluate the role of social support in adherence to healthy Mediterranean diet., (© The Author(s) 2020.)
Published: 2020
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27. Repeated leftover serosurvey of SARS-CoV-2 IgG antibodies, Greece, March and April 2020.

Author: Bogogiannidou Z, Vontas A, Dadouli K, Kyritsi MA, Soteriades S, Nikoulis DJ, Mouchtouri VΑ, Koureas M, Kazakos EI, Spanos EG, Gioula G, Ntzani EE, Eleftheriou AA, Vatopoulos A, Petinaki E, Papaevangelou V, Speletas M, Tsiodras S, and Hadjichristodoulou C
Subjects: Adolescent, Adult, Age Distribution, Aged, Antibodies, Viral blood, Betacoronavirus, COVID-19, Child, Child, Preschool, Coronavirus isolation & purification, Coronavirus Infections virology, Female, Greece epidemiology, Humans, Infant, Infant, Newborn, Male, Middle Aged, Pandemics, Pneumonia, Viral virology, Prevalence, SARS-CoV-2, Seroepidemiologic Studies, Sex Distribution, Young Adult, Coronavirus immunology, Coronavirus Infections epidemiology, Immunoglobulin G blood, Pneumonia, Viral epidemiology
Abstract: A serosurvey of IgG antibodies against severe acute respiratory coronavirus 2 (SARS-CoV-2) was performed during March and April 2020. Among 6,586 leftover sera, 24 (0.36%) were positive, with higher prevalence in females, older individuals and residents of large urban areas. Seroprevalence was estimated at 0.02% and 0.25%, respectively, in March and April, infection fatality rate at 2.66% and 0.54%. Our findings confirm low COVID-19 incidence in Greece and possibly the effectiveness of early measures.
Published: 2020
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28. A genome-wide scan for pleiotropy between bone mineral density and nonbone phenotypes.

Author: Christou MA, Ntritsos G, Markozannes G, Koskeridis F, Nikas SN, Karasik D, Kiel DP, Evangelou E, and Ntzani EE
Abstract: Osteoporosis is the most common metabolic bone disorder globally and is characterized by skeletal fragility and microarchitectural deterioration. Genetic pleiotropy occurs when a single genetic element is associated with more than one phenotype. We aimed to identify pleiotropic loci associated with bone mineral density (BMD) and nonbone phenotypes in genome-wide association studies. In the discovery stage, the NHGRI-EBI Catalog was searched for genome-wide significant associations ( P value < 5 × 10 -8 ), excluding bone-related phenotypes. SNiPA was used to identify proxies of the significantly associated single nucleotide polymorphisms (SNPs) ( r 2 = 1). We then assessed putative genetic associations of this set of SNPs with femoral neck (FN) and lumbar spine (LS) BMD data from the GEFOS Consortium. Pleiotropic variants were claimed at a false discovery rate < 1.4 × 10 -3 for FN-BMD and < 1.5 × 10 -3 for LS-BMD. Replication of these genetic markers was performed among more than 400 000 UK Biobank participants of European ancestry with available genetic and heel bone ultrasound data. In the discovery stage, 72 BMD-related pleiotropic SNPs were identified, and 12 SNPs located in 11 loci on 8 chromosomes were replicated in the UK Biobank. These SNPs were associated, in addition to BMD, with 14 different phenotypes. Most pleiotropic associations were exhibited by rs479844 ( AP5B1, OVOL1 genes), which was associated with dermatological and allergic diseases, and rs4072037 ( MUC1 gene), which was associated with magnesium levels and gastroenterological cancer. In conclusion, 12 BMD-related genome-wide significant SNPs showed pleiotropy with nonbone phenotypes. Pleiotropic associations can deepen the genetic understanding of bone-related diseases by identifying shared biological mechanisms with other diseases or traits., Competing Interests: Competing interestsDr. Kiel’s time was supported by a grant from NIAMS R01 AR041398. All remaining authors declare no competing interests., (© The Author(s) 2020.)
Published: 2020
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29. Atherogenic dyslipidemia increases the risk of incident diabetes in statin-treated patients with impaired fasting glucose or obesity.

Author: Barkas F, Elisaf M, Liberopoulos E, Liamis G, Ntzani EE, and Rizos EC
Subjects: Adult, Atherosclerosis complications, Atherosclerosis drug therapy, Dyslipidemias complications, Dyslipidemias drug therapy, Fasting blood, Female, Greece, Humans, Lipids, Male, Middle Aged, Obesity complications, Obesity drug therapy, Prediabetic State blood, Prediabetic State drug therapy, Retrospective Studies, Risk Factors, Atherosclerosis blood, Blood Glucose analysis, Diabetes Mellitus, Type 2 chemically induced, Dyslipidemias blood, Hydroxymethylglutaryl-CoA Reductase Inhibitors adverse effects, Obesity blood
Abstract: Aim: To investigate which metabolic factors increase the risk of incident diabetes (T2D) in statin-treated patients., Methods: A retrospective study conducted in Greece including 1241 consecutive individuals with dyslipidemia attending a lipid clinic for ≥3 years. After defining associations with incident T2D, we assessed the risk of new-onset T2D based on the presence of impaired fasting glucose (IFG), atherogenic dyslipidemia, and overweight/obesity., Results: After excluding 166 patients with baseline T2D and 193 subjects taking lipid-lowering therapy at the baseline visit, 882 participants were included in the study. Eleven percent (n=94) developed T2D during their follow-up (median 6 years; IQR: 4-10). Baseline patients' age (OR: 1.05; 95% CI: 1.02-1.08, p<0.01), family history of diabetes (OR: 3.58; 95% CI: 1.86-6.91, p<0.01), IFG (OR: 6.56; 95% CI: 3.53-12.12, p<0.01), overweight/obesity (OR: 2.65; 95% CI: 1.39-5.05, p<0.01), atherogenic dyslipidemia (OR: 3.27; 95% CI: 1.50-7.15, p<0.01), and treatment with high-intensity statins (OR: 3.51; 95% CI: 1.89-6.51, p<0.01) were independently associated with increased risk of T2D in statin-treated patients. Among the IFG subjects, atherogenic dyslipidemia (OR: 3.44; 95% CI: 1.31-9.04, p=0.01) and overweight/obesity (OR: 2.54; 95% CI: 1.14-5.66, p<0.05) independently increased the risk of T2D. Among the overweight/obese ones, atherogenic dyslipidemia independently increased the risk of T2D (adjusted OR: 5.60; 95% CI: 2.19-14.30, p<0.01)., Conclusion: Atherogenic dyslipidemia appears to be an independent risk factor for new-onset T2D in statin-treated patients, while IFG, overweight/obesity and family history of diabetes remain risk factors for new-onset T2D in this group., (Copyright © 2019 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)
Published: 2019
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30. Association between blood pressure and risk of cancer development: a systematic review and meta-analysis of observational studies.

Author: Seretis A, Cividini S, Markozannes G, Tseretopoulou X, Lopez DS, Ntzani EE, and Tsilidis KK
Subjects: Female, Humans, Male, Risk Factors, Blood Pressure, Hypertension complications, Hypertension epidemiology, Hypertension physiopathology, Neoplasms epidemiology, Neoplasms etiology, Neoplasms physiopathology
Abstract: With the exception of renal cell carcinoma, studies assessing the association between hypertension and other cancers are inconsistent. We conducted a meta-analysis to assess this evidence. We included observational studies investigating the association between any definition of hypertension or systolic and diastolic blood pressure and risk of any cancer, after searching PubMed until November 2017. We calculated summary relative risks (RR) and 95% confidence intervals (CI) using inverse-variance weighted random effects methods. A total of 148 eligible publications were identified out of 39,891 initially screened citations. Considering only evidence from 85 prospective studies, positive associations were observed between hypertension and kidney, colorectal and breast cancer. Positive associations between hypertension and risk of oesophageal adenocarcinoma and squamous cell carcinoma, liver and endometrial cancer were also observed, but the majority of studies did not perform comprehensive multivariable adjustments. Systolic and diastolic blood pressure were positively associated with risk of kidney cancer but not with other cancers. In addition to the previously well-described association between hypertension and risk of kidney cancer, the current meta-analysis suggested that hypertensive individuals may also be at higher risk of colorectal and breast cancer. However, careful interpretation is required as most meta-analyses included relatively small number of studies, several relative risks had weak or moderate magnitude and maybe affected by residual confounding.
Published: 2019
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31. Burden of hip fracture using disability-adjusted life-years: a pooled analysis of prospective cohorts in the CHANCES consortium.

Author: Papadimitriou N, Tsilidis KK, Orfanos P, Benetou V, Ntzani EE, Soerjomataram I, Künn-Nelen A, Pettersson-Kymmer U, Eriksson S, Brenner H, Schöttker B, Saum KU, Holleczek B, Grodstein FD, Feskanich D, Orsini N, Wolk A, Bellavia A, Wilsgaard T, Jørgensen L, Boffetta P, Trichopoulos D, and Trichopoulou A
Subjects: Aged, Europe epidemiology, Female, Humans, Male, Middle Aged, Prospective Studies, Risk Factors, United States epidemiology, Cost of Illness, Disabled Persons statistics & numerical data, Hip Fractures epidemiology, Quality-Adjusted Life Years
Abstract: Background: No studies have estimated disability-adjusted life-years (DALYs) lost due to hip fractures using real-life follow-up cohort data. We aimed to quantify the burden of disease due to incident hip fracture using DALYs in prospective cohorts in the CHANCES consortium, and to calculate population attributable fractions based on DALYs for specific risk factors., Methods: We used data from six cohorts of participants aged 50 years or older at recruitment to calculate DALYs. We applied disability weights proposed by the National Osteoporosis Foundation and did a series of sensitivity analyses to examine the robustness of DALY estimates. We calculated population attributable fractions for smoking, body-mass index (BMI), physical activity, alcohol intake, type 2 diabetes and parity, use of hormone replacement therapy, and oral contraceptives in women. We calculated summary risk estimates across cohorts with pooled analysis and random-effects meta-analysis methods., Findings: 223 880 men and women were followed up for a mean of 13 years (SD 6). 7724 (3·5%) participants developed an incident hip fracture, of whom 413 (5·3%) died as a result. 5964 DALYs (27 per 1000 individuals) were lost due to hip fractures, 1230 (20·6%) of which were in the group aged 75-79 years. 4150 (69·6%) DALYs were attributed to disability. Current smoking was the risk factor responsible for the greatest hip fracture burden (7·5%, 95% CI 5·2-9·7) followed by physical inactivity (5·5%, 2·1-8·5), history of diabetes (2·8%, 2·1-4·0), and low to average BMI (2·0%, 1·4-2·7), whereas low alcohol consumption (0·01-2·5 g per day) and high BMI had a protective effect., Interpretation: Hip fracture can lead to a substantial loss of healthy life-years in elderly people. National public health policies should be strengthened to reduce hip fracture incidence and mortality. Primary prevention measures should be strengthened to prevent falls, and reduce smoking and a sedentary lifestyle., Funding: European Community's Seventh Framework Programme., (Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND license. Published by Elsevier Ltd.. All rights reserved.)
Published: 2017
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32. Exposure to pesticides and diabetes: A systematic review and meta-analysis.

Author: Evangelou E, Ntritsos G, Chondrogiorgi M, Kavvoura FK, Hernández AF, Ntzani EE, and Tzoulaki I
Subjects: Case-Control Studies, Cohort Studies, Cross-Sectional Studies, Humans, Diabetes Mellitus, Type 2 epidemiology, Environmental Exposure analysis, Environmental Pollutants analysis, Hydrocarbons, Chlorinated analysis, Pesticides analysis
Abstract: Background: Diabetes mellitus has a multifactorial pathogenesis with a strong genetic component as well as many environmental and lifestyle influences. Emerging evidence suggests that environmental contaminants, including pesticides, might play an important role in the pathogenesis of diabetes., Objectives: We performed a systematic review and meta-analysis of observational studies that assessed the association between exposure to pesticides and diabetes and we examined the presence of heterogeneity and biases across available studies., Methods: A comprehensive literature search of peer-reviewed original research pertaining to pesticide exposure and diabetes, published until 30st May 2015, with no language restriction, was conducted. Eligible studies were those that investigated potential associations between pesticides and diabetes without restrictions on diabetes type. We included cohort studies, case-control studies and cross-sectional studies. We extracted information on study characteristics, type of pesticide assessed, exposure assessment, outcome definition, effect estimate and sample size., Results: We identified 22 studies assessing the association between pesticides and diabetes. The summary OR for the association of top vs. bottom tertile of exposure to any type of pesticide and diabetes was 1.58 (95% CI: 1.32-1.90, p=1.21×10(-6)), with large heterogeneity (I(2)=66.8%). Studies evaluating Type 2 diabetes in particular (n=13 studies), showed a similar summary effect comparing top vs. bottom tertiles of exposure: 1.61 (95% CI 1.37-1.88, p=3.51×10(-9)) with no heterogeneity (I(2)=0%). Analysis by type of pesticide yielded an increased risk of diabetes for DDE, heptachlor, HCB, DDT, and trans-nonachlor or chlordane., Conclusions: The epidemiological evidence, supported by mechanistic studies, suggests an association between exposure to organochlorine pesticides and Type 2 diabetes., (Copyright © 2016 Elsevier Ltd. All rights reserved.)
Published: 2016
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33. Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture.

Author: Zheng HF, Forgetta V, Hsu YH, Estrada K, Rosello-Diez A, Leo PJ, Dahia CL, Park-Min KH, Tobias JH, Kooperberg C, Kleinman A, Styrkarsdottir U, Liu CT, Uggla C, Evans DS, Nielson CM, Walter K, Pettersson-Kymmer U, McCarthy S, Eriksson J, Kwan T, Jhamai M, Trajanoska K, Memari Y, Min J, Huang J, Danecek P, Wilmot B, Li R, Chou WC, Mokry LE, Moayyeri A, Claussnitzer M, Cheng CH, Cheung W, Medina-Gómez C, Ge B, Chen SH, Choi K, Oei L, Fraser J, Kraaij R, Hibbs MA, Gregson CL, Paquette D, Hofman A, Wibom C, Tranah GJ, Marshall M, Gardiner BB, Cremin K, Auer P, Hsu L, Ring S, Tung JY, Thorleifsson G, Enneman AW, van Schoor NM, de Groot LC, van der Velde N, Melin B, Kemp JP, Christiansen C, Sayers A, Zhou Y, Calderari S, van Rooij J, Carlson C, Peters U, Berlivet S, Dostie J, Uitterlinden AG, Williams SR, Farber C, Grinberg D, LaCroix AZ, Haessler J, Chasman DI, Giulianini F, Rose LM, Ridker PM, Eisman JA, Nguyen TV, Center JR, Nogues X, Garcia-Giralt N, Launer LL, Gudnason V, Mellström D, Vandenput L, Amin N, van Duijn CM, Karlsson MK, Ljunggren Ö, Svensson O, Hallmans G, Rousseau F, Giroux S, Bussière J, Arp PP, Koromani F, Prince RL, Lewis JR, Langdahl BL, Hermann AP, Jensen JE, Kaptoge S, Khaw KT, Reeve J, Formosa MM, Xuereb-Anastasi A, Åkesson K, McGuigan FE, Garg G, Olmos JM, Zarrabeitia MT, Riancho JA, Ralston SH, Alonso N, Jiang X, Goltzman D, Pastinen T, Grundberg E, Gauguier D, Orwoll ES, Karasik D, Davey-Smith G, Smith AV, Siggeirsdottir K, Harris TB, Zillikens MC, van Meurs JB, Thorsteinsdottir U, Maurano MT, Timpson NJ, Soranzo N, Durbin R, Wilson SG, Ntzani EE, Brown MA, Stefansson K, Hinds DA, Spector T, Cupples LA, Ohlsson C, Greenwood CM, Jackson RD, Rowe DW, Loomis CA, Evans DM, Ackert-Bicknell CL, Joyner AL, Duncan EL, Kiel DP, Rivadeneira F, and Richards JB
Subjects: Animals, Bone and Bones metabolism, Disease Models, Animal, Europe ethnology, Exome genetics, Female, Gene Frequency genetics, Genetic Predisposition to Disease genetics, Genetic Variation genetics, Genomics, Genotype, Humans, Mice, Sequence Analysis, DNA, White People genetics, Wnt Proteins genetics, Bone Density genetics, Fractures, Bone genetics, Genome, Human genetics, Homeodomain Proteins genetics
Abstract: The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF ≤ 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants, as well as rare, population-specific, coding variants. Here we identify novel non-coding genetic variants with large effects on BMD (ntotal = 53,236) and fracture (ntotal = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD (rs11692564(T), MAF = 1.6%, replication effect size = +0.20 s.d., Pmeta = 2 × 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 × 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1(cre/flox) mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low-frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size = +0.41 s.d., Pmeta = 1 × 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.
Published: 2015
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34. Assessment of osteoarthritis candidate genes in a meta-analysis of nine genome-wide association studies.

Author: Rodriguez-Fontenla C, Calaza M, Evangelou E, Valdes AM, Arden N, Blanco FJ, Carr A, Chapman K, Deloukas P, Doherty M, Esko T, Garcés Aletá CM, Gomez-Reino Carnota JJ, Helgadottir H, Hofman A, Jonsdottir I, Kerkhof HJ, Kloppenburg M, McCaskie A, Ntzani EE, Ollier WE, Oreiro N, Panoutsopoulou K, Ralston SH, Ramos YF, Riancho JA, Rivadeneira F, Slagboom PE, Styrkarsdottir U, Thorsteinsdottir U, Thorleifsson G, Tsezou A, Uitterlinden AG, Wallis GA, Wilkinson JM, Zhai G, Zhu Y, Felson DT, Ioannidis JP, Loughlin J, Metspalu A, Meulenbelt I, Stefansson K, van Meurs JB, Zeggini E, Spector TD, and Gonzalez A
Subjects: Collagen Type XI genetics, Gene Frequency, Genome-Wide Association Study, Genotype, Humans, Vascular Endothelial Growth Factor A genetics, Genetic Predisposition to Disease, Osteoarthritis, Hip genetics, Osteoarthritis, Knee genetics, Polymorphism, Single Nucleotide
Abstract: Objective: To assess candidate genes for association with osteoarthritis (OA) and identify promising genetic factors and, secondarily, to assess the candidate gene approach in OA., Methods: A total of 199 candidate genes for association with OA were identified using Human Genome Epidemiology (HuGE) Navigator. All of their single-nucleotide polymorphisms (SNPs) with an allele frequency of >5% were assessed by fixed-effects meta-analysis of 9 genome-wide association studies (GWAS) that included 5,636 patients with knee OA and 16,972 control subjects and 4,349 patients with hip OA and 17,836 control subjects of European ancestry. An additional 5,921 individuals were genotyped for significantly associated SNPs in the meta-analysis. After correction for the number of independent tests, P values less than 1.58 × 10(-5) were considered significant., Results: SNPs at only 2 of the 199 candidate genes (COL11A1 and VEGF) were associated with OA in the meta-analysis. Two SNPs in COL11A1 showed association with hip OA in the combined analysis: rs4907986 (P = 1.29 × 10(-5) , odds ratio [OR] 1.12, 95% confidence interval [95% CI] 1.06-1.17) and rs1241164 (P = 1.47 × 10(-5) , OR 0.82, 95% CI 0.74-0.89). The sex-stratified analysis also showed association of COL11A1 SNP rs4908291 in women (P = 1.29 × 10(-5) , OR 0.87, 95% CI 0.82-0.92); this SNP showed linkage disequilibrium with rs4907986. A single SNP of VEGF, rs833058, showed association with hip OA in men (P = 1.35 × 10(-5) , OR 0.85, 95% CI 0.79-0.91). After additional samples were genotyped, association at one of the COL11A1 signals was reinforced, whereas association at VEGF was slightly weakened., Conclusion: Two candidate genes, COL11A1 and VEGF, were significantly associated with OA in this focused meta-analysis. The remaining candidate genes were not associated., (Copyright © 2014 by the American College of Rheumatology.)
Published: 2014
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35. CER1 gene variations associated with bone mineral density, bone markers, and early menopause in postmenopausal women.

Author: Koromila T, Georgoulias P, Dailiana Z, Ntzani EE, Samara S, Chassanidis C, Aleporou-Marinou V, and Kollia P
Subjects: Aged, Aged, 80 and over, Calcitonin blood, Case-Control Studies, Female, Gene Expression Regulation, Humans, Insulin-Like Growth Factor I metabolism, Logistic Models, Middle Aged, Osteocalcin blood, Parathyroid Hormone blood, Polymorphism, Genetic, Bone Density genetics, Cytokines genetics, Genetic Variation, Intercellular Signaling Peptides and Proteins genetics, Osteoporosis genetics, Postmenopause
Abstract: Background: Osteoporosis has a multifactorial pathogenesis characterized by a combination of low bone mass and increased fragility. In our study, we focused on the effects of polymorphisms in CER1 and DKK1 genes, recently reported as important susceptibility genes for osteoporosis, on bone mineral density (BMD) and bone markers in osteoporotic women. Our objective was to evaluate the effect of CER1 and DKK1 variations in 607 postmenopausal women. The entire DKK1 gene sequence and five selected CER1 SNPs were amplified and resequenced to assess whether there is a correlation between these genes and BMD, early menopause, and bone turnover markers in osteoporotic patients., Results: Osteoporotic women seem to suffer menopause 2 years earlier than the control group. The entire DKK1 gene sequence analysis revealed six variations. There was no correlation between the six DKK1 variations and osteoporosis, in contrast to the five common CER1 variations that were significantly associated with BMD. Additionally, osteoporotic patients with rs3747532 and rs7022304 CER1 variations had significantly higher serum levels of parathyroid hormone and calcitonin and lower serum levels of osteocalcin and IGF-1., Conclusions: No significant association between the studied DKK1 variations and osteoporosis was found, while CER1 variations seem to play a significant role in the determination of osteoporosis and a potential predictive role, combined with bone markers, in postmenopausal osteoporotic women.
Published: 2013
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36. A novel oral nutraceutical formula of omega-3 and omega-6 fatty acids with vitamins (PLP10) in relapsing remitting multiple sclerosis: a randomised, double-blind, placebo-controlled proof-of-concept clinical trial.

Author: Pantzaris MC, Loukaides GN, Ntzani EE, and Patrikios IS
Abstract: Objective: To assess whether three novel interventions, formulated based on a systems medicine therapeutic concept, reduced disease activity in patients with relapsing-remitting multiple sclerosis (MS) who were either treated or not with disease-modifying treatment., Design: A 30-month randomised, double-blind, placebo-controlled, parallel design, phase II proof-of-concept clinical study., Settings: Cyprus Institute of Neurology and Genetics., Participants: 80 participants were randomised into four groups of 20 each. A total of 41 (51%) patients completed the 30-month trial. The eligibility criteria were an age of 18-65; a diagnosis of relapsing-remitting MS according to the McDonald criteria; a score of 0.0-5.5 on the Expanded Disability Status Scale (EDSS); MRI showing lesions consistent with MS; at least one documented clinical relapse and either receiving or not a disease-modifying treatment within the 24-month period before enrolment in the study. Patients were excluded because of a recent (<30 days) relapse, prior immunosuppressant or monoclonal antibody therapy, pregnancy or nursing, other severe disease compromising organ function, progressive MS, history of recent drug or alcohol abuse, use of any additional food supplements, vitamins or any form of polyunsaturated fatty acids, and a history of severe allergic or anaphylactic reactions or known specific nutritional hypersensitivity., Interventions: The first intervention (A) was composed of Ω-3 and Ω-6 polyunsaturated fatty acids at 1:1 wt/wt. Specifically, the Ω-3 fatty acids were docosahexaenoic acid and eicosapentaenoic acid at 3:1 wt/wt, and the Ω-6 fatty acids were linoleic acid and γ-linolenic acid at 2:1 wt/wt. This intervention also included minor quantities of other specific polyunsaturated, monounsaturated and saturated fatty acids as well as vitamin A and vitamin E (α-tocopherol). The second intervention (B, PLP10) was a combination of A and γ-tocopherol. The third intervention (C) was γ-tocopherol alone. The fourth group of 20 participants received placebo. The interventions were administered per os (by mouth) once daily, 30 min before dinner for 30 months., Main Outcome Measures: The primary end point was the annualised relapse rate (ARR) of the three interventions versus the placebo at 2 years. The secondary end point was the time to confirmed disability progression at 2 years., Results: A total of 41 (51%) patients completed the 30-month trial. Overall, for the per-protocol analysis of the 2-year primary end point, eight relapses were recorded in the PLP10 group (n=10; 0.40 ARR) versus 25 relapses in the placebo group (n=12; 1.04 ARR), representing a 64% adjusted relative rate reduction for the PLP10 group (RRR 0.36, 95% CI 0.15 to 0.87, p=0.024). In a subgroup analysis that excluded patients on monoclonal antibody (natalizumab) treatment, the observed adjusted RRR became stronger (72%) over the 2 years (RRR 0.28, 95% CI 0.10 to 0.79, p=0.016). The per-protocol analysis for the secondary outcome at 2 years, the time to disability progression, was significantly longer only for PLP10. The cumulative probability of disability progression at 2 years was 10% in the PLP10 group and 58% in the placebo group (unadjusted log-rank p=0.019). In a subgroup analysis that excluded patients on natalizumab, the cumulative probability of progression was 10% for the 10 patients in the PLP10 group and 70% for the 12 patients in the placebo group, representing a relative 86% decrease in the risk of the sustained progression of disability in the PLP10 group (unadjusted log-rank p=0.006; adjusted HR, 0.11; 95% CI 0.01 to 0.97, p=0.047). No adverse events were reported. Interventions A (10 patients) and C (9 patients) showed no significant efficacy., Conclusions: In this small proof-of-concept, randomised, double-blind clinical trial; the PLP10 treatment significantly reduced the ARR and the risk of sustained disability progression without any reported serious adverse events. Larger studies are needed to further assess the safety and efficacy of PLP10., Trial Registration: International Standard Randomised Controlled Trial, number ISRCTN87818535.
Published: 2013
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37. Consistency of genome-wide associations across major ancestral groups.

Author: Ntzani EE, Liberopoulos G, Manolio TA, and Ioannidis JP
Subjects: Gene Frequency, Genetic Markers, Genome-Wide Association Study, Genotype, Humans, Polymorphism, Single Nucleotide, Risk Factors, Asian People genetics, Black People genetics, Genetic Predisposition to Disease, Genome, Human, White People genetics
Abstract: It is not well known whether genetic markers identified through genome-wide association studies (GWAS) confer similar or different risks across people of different ancestry. We screened a regularly updated catalog of all published GWAS curated at the NHGRI website for GWAS-identified associations that had reached genome-wide significance (p ≤ 5 × 10(-8)) in at least one major ancestry group (European, Asian, African) and for which replication data were available for comparison in at least two different major ancestry groups. These groups were compared for the correlation between and differences in risk allele frequencies and genetic effects' estimates. Data on 108 eligible GWAS-identified associations with a total of 900 datasets (European, n = 624; Asian, n = 217; African, n = 60) were analyzed. Risk-allele frequencies were modestly correlated between ancestry groups, with >10% absolute differences in 75-89% of the three pairwise comparisons of ancestry groups. Genetic effect (odds ratio) point estimates between ancestry groups correlated modestly (pairwise comparisons' correlation coefficients: 0.20-0.33) and point estimates of risks were opposite in direction or differed more than twofold in 57%, 79%, and 89% of the European versus Asian, European versus African, and Asian versus African comparisons, respectively. The modest correlations, differing risk estimates, and considerable between-association heterogeneity suggest that differential ancestral effects can be anticipated and genomic risk markers may need separate further evaluation in different ancestry groups.
Published: 2012
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38. Malignant mesothelioma in Metsovo, Greece, from domestic use of asbestos: 30 years later.

Author: Gogali A, Manda-Stachouli C, Ntzani EE, Matthaiou M, Konstantinidis AK, Zampira I, Koubaniou C, Dalavanga Y, Stefanou D, Constantopoulos SH, and Daskalopoulos G
Subjects: Aged, Aged, 80 and over, Environmental Exposure, Female, Follow-Up Studies, Greece, Humans, Incidence, Male, Middle Aged, Risk, Time Factors, Asbestos adverse effects, Mesothelioma epidemiology, Mesothelioma etiology, Pleural Neoplasms epidemiology, Pleural Neoplasms etiology
Published: 2012
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39. Different black box warning labeling for same-class drugs.

Author: Panagiotou OA, Contopoulos-Ioannidis DG, Papanikolaou PN, Ntzani EE, and Ioannidis JP
Subjects: Databases, Factual, Drug Labeling methods, Humans, Safety-Based Drug Withdrawals methods, United States, United States Food and Drug Administration standards, Drug Labeling standards, Drug-Related Side Effects and Adverse Reactions, Pharmaceutical Preparations classification
Abstract: Introduction: Black box warnings (BBWs) are the strongest medication-related safety warnings in a drug's labeling information and highlight major risks. Absence of a BBW or asynchronous addition of a BBW among same-class drugs could have major implications., Methods: We identified the 20 top-selling drugs in 2008 (10 with BBWs and 10 without BBWs on their label) that belonged to different drug classes. We collected labeling information on all drugs belonging in these 20 classes, and recorded differences in the presence and timing of acquisition of BBWs for same-class drugs., Results: Across the 20 evaluated drug classes, we identified 176 different agents, of which 7 had been withdrawn for safety reasons. The reasons for the withdrawals became BBWs in other same-class agents only in two of the seven cases. Differences were identified in 9 of the 20 classes corresponding to 15 BBWs that were not present in all drugs of the same class. The information for 10 of the 15 different BBWs were included in the labels of same-class drugs as simple warnings or text, while it was absent entirely in 5 BBWs. The median interval from the time the BBW had appeared in another drug of the same class was 66 months., Discussion: Differences in BBW labeling in same-class drugs are common and shape impressions about the safety of similar agents. BBW labeling needs to become more systematic.
Published: 2011
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40. Association of RGS4 variants with schizotypy and cognitive endophenotypes at the population level.

Author: Stefanis NC, Trikalinos TA, Avramopoulos D, Smyrnis N, Evdokimidis I, Ntzani EE, Hatzimanolis A, Ioannidis JP, and Stefanis CN
Abstract: Background: While association studies on schizophrenia show conflicting results regarding the importance of the regulator of the G-protein signaling 4 (RGS4) gene, recent work suggests that RGS4 may impact on the structural and functional integrity of the prefrontal cortex. We aimed to study associations of common RGS4 variants with prefrontal dependent cognitive performance and schizotypy endophenotypes at the population level., Methods: Four RGS4 single nucleotide polymorphisms (SNP1 [rs10917670], SNP4 [rs951436], SNP7 [rs951439], and SNP18 [rs2661319]) and their haplotypes were selected. Their associations with self-rated schizotypy (SPQ), vigilance, verbal, spatial working memory and antisaccade eye performance were tested with regressions in a representative population of 2,243 young male military conscripts., Results: SNP4 was associated with negative schizotypy (higher SPQ negative factor for common T allele, p = 0.009; p = 0.031 for differences across genotypes) and a similar trend was seen also for common A allele of SNP18 (p = 0.039 for allele-load model; but p = 0.12 for genotype differences). Haplotype analyses showed a similar pattern with a dose-response for the most common haplotype (GGGG) on the negative schizotypy score with or without adjustment for age, IQ and their interaction (p = 0.011 and p = 0.024, respectively). There was no clear evidence for any association of the RGS4 variants with cognitive endophenotypes, except for an isolated effect of SNP18 on antisaccade error rate (p = 0.028 for allele-load model)., Conclusion: Common RGS4 variants were associated with negative schizotypal personality traits amongst a large cohort of young healthy individuals. In accordance with recent findings, this may suggest that RGS4 variants impact on the functional integrity of the prefrontal cortex, thus increasing susceptibility for psychotic spectrum disorders.
Published: 2008
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41. Hardy-Weinberg equilibrium in genetic association studies: an empirical evaluation of reporting, deviations, and power.

Author: Salanti G, Amountza G, Ntzani EE, and Ioannidis JP
Subjects: Databases as Topic, Gene Frequency, Humans, Periodicals as Topic, Sample Size, Linkage Disequilibrium, Models, Genetic, Models, Statistical
Abstract: We evaluated the testing and reporting of Hardy-Weinberg equilibrium (HWE) in recent genetic association studies, detected how frequently HWE was violated and estimated the power for HWE testing in this literature. Genetic association studies published in 2002 in Nature Genetics, American Journal of Human Genetics, and American Journal of Medical Genetics were assessed. Data were analyzed on 239 biallelic associations using 154 distinct genotype distribution data sets where HWE could be tested. Any information on HWE was given only for 150 (62.8%) associations (92 (59.7%) data sets). Reanalysis of the data showed significant deviation from HWE in the disease-free controls of 20 associations (13 data sets), but only four of them (two data sets) were admitted in the published articles. Another four deviations (in two data sets) were observed in the combined sample of cases and controls of studies where both cases and controls were diseased, and none were reported in the papers. In all six tested multiallelic associations (six data sets), there was violation of HWE, but this was not admitted in the published articles. Power calculations showed that most studies conforming to HWE simply were largely underpowered to detect HWE deviation; for example, power to detect an inbreeding of magnitude F=0.10 exceeded 80% in only 11 (7%) of the data sets being tested. This empirical evidence suggests that, even in high profile genetics journals, testing and reporting for HWE is often neglected and deviations are rarely admitted in the published reports. Moreover, power is limited for HWE testing in most current genetic association studies.
Published: 2005
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42. Establishment of genetic associations for complex diseases is independent of early study findings.

Author: Trikalinos TA, Ntzani EE, Contopoulos-Ioannidis DG, and Ioannidis JP
Subjects: Databases, Factual, Humans, Odds Ratio, Sensitivity and Specificity, Causality, Genetic Predisposition to Disease, Meta-Analysis as Topic, Publication Bias
Abstract: Numerous genetic association studies for complex diseases are performed. Investigators place emphasis on formal statistical significance (P-values < 0.05), but the predictive ability of early statistically significant ('positive') findings is unclear. We scrutinized 55 cumulative meta-analyses of genetic associations (579 studies), in order to assess whether having statistical significance in the earliest (first) published study or in at least half among several (> or =3) early-published studies, or high statistical significance in early studies had any predictive ability for establishing or refuting the presence of the genetic association in subsequent research. In 35 associations, a first study was 'positive' and in 15 associations more than half of the early-published reports were 'positive'. The average publication rate of subsequent studies increased 1.71-fold with a 'positive' first report. When compared against the summary results of subsequent research, sensitivity and specificity were 0.65 and 0.38 for the first reports, and 0.40 and 0.73, respectively, when at least three early studies were considered. First studies also had poor predictive ability, when we considered the estimated attributable fraction and coverage of the 95% confidence interval thereof or higher levels of statistical significance. We conclude that although 'positive' findings in the very first reports provide strong incentive for conducting more studies on a putative genetic epidemiological association, the statistical significance or even the magnitude of the effect of early studies cannot adequately predict eventual establishment of an association. Conversely, many genuine epidemiological associations would be missed, if research were abandoned after early underpowered 'negative' studies.
Published: 2004
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