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The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study.

About this Publication
Title
The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study.
Pubmed ID
26426971 (View this publication on the PubMed website)
Publication
PLoS Genet. 2015 Oct; Volume 11 (Issue 10): Pages e1005378
Authors
Winkler TW, Justice AE, Graff M, Barata L, Feitosa MF, Chu S, Czajkowski J, Esko T, Fall T, Kilpeläinen TO, Lu Y, Mägi R, Mihailov E, Pers TH, Rüeger S, Teumer A, Ehret GB, Ferreira T, Heard-Costa NL, Karjalainen J, ...show more Lagou V, Mahajan A, Neinast MD, Prokopenko I, Simino J, Teslovich TM, Jansen R, Westra HJ, White CC, Absher D, Ahluwalia TS, Ahmad S, Albrecht E, Alves AC, Bragg-Gresham JL, de Craen AJ, Bis JC, Bonnefond A, Boucher G, Cadby G, Cheng YC, Chiang CW, Delgado G, Demirkan A, Dueker N, Eklund N, Eiriksdottir G, Eriksson J, Feenstra B, Fischer K, Frau F, Galesloot TE, Geller F, Goel A, Gorski M, Grammer TB, Gustafsson S, Haitjema S, Hottenga JJ, Huffman JE, Jackson AU, Jacobs KB, Johansson Å, Kaakinen M, Kleber ME, Lahti J, Mateo Leach I, Lehne B, Liu Y, Lo KS, Lorentzon M, Luan J, Madden PA, Mangino M, McKnight B, Medina-Gomez C, Monda KL, Montasser ME, Müller G, Müller-Nurasyid M, Nolte IM, Panoutsopoulou K, Pascoe L, Paternoster L, Rayner NW, Renström F, Rizzi F, Rose LM, Ryan KA, Salo P, Sanna S, Scharnagl H, Shi J, Smith AV, Southam L, Stančáková A, Steinthorsdottir V, Strawbridge RJ, Sung YJ, Tachmazidou I, Tanaka T, Thorleifsson G, Trompet S, Pervjakova N, Tyrer JP, Vandenput L, van der Laan SW, van der Velde N, van Setten J, van Vliet-Ostaptchouk JV, Verweij N, Vlachopoulou E, Waite LL, Wang SR, Wang Z, Wild SH, Willenborg C, Wilson JF, Wong A, Yang J, Yengo L, Yerges-Armstrong LM, Yu L, Zhang W, Zhao JH, Andersson EA, Bakker SJ, Baldassarre D, Banasik K, Barcella M, Barlassina C, Bellis C, Benaglio P, Blangero J, Blüher M, Bonnet F, Bonnycastle LL, Boyd HA, Bruinenberg M, Buchman AS, Campbell H, Chen YD, Chines PS, Claudi-Boehm S, Cole J, Collins FS, de Geus EJ, de Groot LC, Dimitriou M, Duan J, Enroth S, Eury E, Farmaki AE, Forouhi NG, Friedrich N, Gejman PV, Gigante B, Glorioso N, Go AS, Gottesman O, Gräßler J, Grallert H, Grarup N, Gu YM, Broer L, Ham AC, Hansen T, Harris TB, Hartman CA, Hassinen M, Hastie N, Hattersley AT, Heath AC, Henders AK, Hernandez D, Hillege H, Holmen O, Hovingh KG, Hui J, Husemoen LL, Hutri-Kähönen N, Hysi PG, Illig T, De Jager PL, Jalilzadeh S, Jørgensen T, Jukema JW, Juonala M, Kanoni S, Karaleftheri M, Khaw KT, Kinnunen L, Kittner SJ, Koenig W, Kolcic I, Kovacs P, Krarup NT, Kratzer W, Krüger J, Kuh D, Kumari M, Kyriakou T, Langenberg C, Lannfelt L, Lanzani C, Lotay V, Launer LJ, Leander K, Lindström J, Linneberg A, Liu YP, Lobbens S, Luben R, Lyssenko V, Männistö S, Magnusson PK, McArdle WL, Menni C, Merger S, Milani L, Montgomery GW, Morris AP, Narisu N, Nelis M, Ong KK, Palotie A, Pérusse L, Pichler I, Pilia MG, Pouta A, Rheinberger M, Ribel-Madsen R, Richards M, Rice KM, Rice TK, Rivolta C, Salomaa V, Sanders AR, Sarzynski MA, Scholtens S, Scott RA, Scott WR, Sebert S, Sengupta S, Sennblad B, Seufferlein T, Silveira A, Slagboom PE, Smit JH, Sparsø TH, Stirrups K, Stolk RP, Stringham HM, Swertz MA, Swift AJ, Syvänen AC, Tan ST, Thorand B, Tönjes A, Tremblay A, Tsafantakis E, van der Most PJ, Völker U, Vohl MC, Vonk JM, Waldenberger M, Walker RW, Wennauer R, Widén E, Willemsen G, Wilsgaard T, Wright AF, Zillikens MC, van Dijk SC, van Schoor NM, Asselbergs FW, de Bakker PI, Beckmann JS, Beilby J, Bennett DA, Bergman RN, Bergmann S, Böger CA, Boehm BO, Boerwinkle E, Boomsma DI, Bornstein SR, Bottinger EP, Bouchard C, Chambers JC, Chanock SJ, Chasman DI, Cucca F, Cusi D, Dedoussis G, Erdmann J, Eriksson JG, Evans DA, de Faire U, Farrall M, Ferrucci L, Ford I, Franke L, Franks PW, Froguel P, Gansevoort RT, Gieger C, Grönberg H, Gudnason V, Gyllensten U, Hall P, Hamsten A, van der Harst P, Hayward C, Heliövaara M, Hengstenberg C, Hicks AA, Hingorani A, Hofman A, Hu F, Huikuri HV, Hveem K, James AL, Jordan JM, Jula A, Kähönen M, Kajantie E, Kathiresan S, Kiemeney LA, Kivimaki M, Knekt PB, Koistinen HA, Kooner JS, Koskinen S, Kuusisto J, Maerz W, Martin NG, Laakso M, Lakka TA, Lehtimäki T, Lettre G, Levinson DF, Lind L, Lokki ML, Mäntyselkä P, Melbye M, Metspalu A, Mitchell BD, Moll FL, Murray JC, Musk AW, Nieminen MS, Njølstad I, Ohlsson C, Oldehinkel AJ, Oostra BA, Palmer LJ, Pankow JS, Pasterkamp G, Pedersen NL, Pedersen O, Penninx BW, Perola M, Peters A, Polašek O, Pramstaller PP, Psaty BM, Qi L, Quertermous T, Raitakari OT, Rankinen T, Rauramaa R, Ridker PM, Rioux JD, Rivadeneira F, Rotter JI, Rudan I, den Ruijter HM, Saltevo J, Sattar N, Schunkert H, Schwarz PE, Shuldiner AR, Sinisalo J, Snieder H, Sørensen TI, Spector TD, Staessen JA, Stefania B, Thorsteinsdottir U, Stumvoll M, Tardif JC, Tremoli E, Tuomilehto J, Uitterlinden AG, Uusitupa M, Verbeek AL, Vermeulen SH, Viikari JS, Vitart V, Völzke H, Vollenweider P, Waeber G, Walker M, Wallaschofski H, Wareham NJ, Watkins H, Zeggini E, CHARGE Consortium, DIAGRAM Consortium, GLGC Consortium, Global-BPGen Consortium, ICBP Consortium, MAGIC Consortium, Chakravarti A, Clegg DJ, Cupples LA, Gordon-Larsen P, Jaquish CE, Rao DC, Abecasis GR, Assimes TL, Barroso I, Berndt SI, Boehnke M, Deloukas P, Fox CS, Groop LC, Hunter DJ, Ingelsson E, Kaplan RC, McCarthy MI, Mohlke KL, O'Connell JR, Schlessinger D, Strachan DP, Stefansson K, van Duijn CM, Hirschhorn JN, Lindgren CM, Heid IM, North KE, Borecki IB, Kutalik Z, Loos RJ
Affiliations
  • Department of Genetic Epidemiology, Institute of Epidemiology and Preventive Medicine, University Regensburg, Regensburg, Germany.
  • Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
  • Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, United States of America.
  • Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, United States of America.
  • Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts, United States of America; Divisions of Endocrinology and Genetics and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts, United States of America; Estonian Genome Center, Univeristy of Tartu, Tartu, Estonia; Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America.
  • Science for Life Laboratory, Uppsala University, Uppsala, Sweden; Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala, Sweden.
  • Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom.
  • The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York, United States of America; The Department of Preventive Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
  • Estonian Genome Center, Univeristy of Tartu, Tartu, Estonia; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
  • Estonian Genome Center, Univeristy of Tartu, Tartu, Estonia.
...show more
  • Divisions of Endocrinology and Genetics and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts, United States of America; Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America; Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
  • Swiss Institute of Bioinformatics, Lausanne, Switzerland; Institute of Social and Preventive Medicine, University Hospital Lausanne (CHUV), Lausanne, Switzerland.
  • Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany; Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
  • Department of Specialties of Internal Medicine, Geneva University Hospital, Geneva, Switzerland; Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
  • Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
  • Department of Neurology, Boston University School of Medicine, Boston, Massachusetts, United States of America; National Heart, Lung, and Blood Institute, the Framingham Heart Study, Framingham, Massachusetts, United States of America.
  • University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands.
  • Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, United Kingdom.
  • Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
  • Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, United Kingdom; Hammersmith Hospital, London, United Kingdom; Department of Genomics of Common Diseases, School of Public Health, Imperial College London, London, United Kingdom.
  • Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri, United States of America.
  • Department of Psychiatry and EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, the Netherlands.
  • Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America; Divisions of Genetics and Rheumatology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America; Partners Center for Personalized Genetic Medicine, Boston, Massachusetts, United States of America.
  • Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, United States of America.
  • HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, United States of America.
  • Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Steno Diabetes Center A/S, Gentofte, Denmark; COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
  • Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Skåne University Hospital Malmö, Malmö, Sweden.
  • Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
  • Department of Epidemiology and Biostatistics, MRC Health Protection Agency (HPA) Centre for Environment and Health, School of Public Health, Imperial College, London, United Kingdom.
  • Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.
  • Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, United States of America; Department of Medicine, University of Washington, Seattle, Washington, United States of America.
  • CNRS UMR 8199, Lille, France; European Genomic Institute for Diabetes, Lille, France; Université de Lille 2, Lille, France.
  • Montreal Heart Institute, Montréal, Québec, Canada.
  • Centre for Genetic Origins of Health and Disease, University of Western Australia, Crawley, Western Australia, Australia.
  • VA Maryland Health Care System, Baltimore, Maryland, United States of America; University of Maryland School of Medicine, Department of Medicine, Baltimore, Maryland, United States of America.
  • Department of Ecology and Evolutionary Biology, University of California, Los Angeles, Los Angeles, California, United States of America.
  • Vth Department of Medicine, Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany.
  • Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
  • Universiy of Maryland School of Medicine, Department of Epidemiology & Public Health, Baltimore, Maryland, United States of America.
  • National Institute for Health and Welfare, Department of Chronic Disease Prevention, Helsinki, Finland; National Institute for Health and Welfare, Public Health Genomics Unit, Helsinki, Finland; Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
  • Icelandic Heart Association, Kopavogur, Iceland.
  • Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
  • Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
  • Department of Health Sciences, University of Milan, Milan, Italy; Filarete Foundation, Genomic and Bioinformatics Unit, Milano, Italy.
  • Radboud university medical center, Radboud Institute for Health Sciences, Department for Health Evidence, Nijmegen, The Netherlands.
  • Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Division of Cardiovacular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.
  • Department of Genetic Epidemiology, Institute of Epidemiology and Preventive Medicine, University Regensburg, Regensburg, Germany; Department of Nephrology, University Hospital Regensburg, Regensburg, Germany.
  • Experimental Cardiology and laboratory of clinical chemistry, UMCU, Utrecht, The Netherlands.
  • Department of Biological Psychology, VU University, Amsterdam, The Netherlands.
  • National Heart, Lung, and Blood Institute, the Framingham Heart Study, Framingham, Massachusetts, United States of America; MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, Scotland.
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America; Core Genotyping Facility, SAIC-Frederick, Inc., NCI-Frederick, Frederick, Maryland, United States of America.
  • Science for Life Laboratory, Uppsala University, Uppsala, Sweden; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
  • Department of Epidemiology and Biostatistics, MRC Health Protection Agency (HPA) Centre for Environment and Health, School of Public Health, Imperial College, London, United Kingdom; Institute of Health Sciences, University of Oulu, Oulu, Finland.
  • Folkhälsan Research Centre, Helsinki, Finland; Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.
  • University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, Netherlands.
  • Department of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom.
  • Thurston Arthritis Research Center, University of North Carolina at Chapel Hill, Chaper Hill, North Carolina, United States of America.
  • MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom.
  • Washington University Medical School, St. Louis, Missouri, United States of America.
  • Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom.
  • Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, United States of America; Program in Biostatistics and Biomathematics, Divison of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America; Department of Biostatistics, University of Washington, Seattle, Washington, United States of America.
  • Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), The Netherlands; Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
  • Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America; The Center for Observational Research, Amgen Inc., Thousand Oaks, California, United States of America.
  • Program for Personalized and Genomic Medicine, Division of Endocrinology, Diabetes & Nutrition, Dept of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
  • Center for Evidence Based Healthcare, University of Dresden, Medical Faculty Carl Gustav Carus, Dresden, Germany.
  • Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians-Universität, Munich, Germany; Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany; DZHK (German Centre for Cardiovascular Research), partnersite Munich Heart Alliance, Munich, Germany.
  • University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, The Netherlands.
  • Wellcome Trust Sanger Institute, Human Genetics, Hinxton, Cambridge, United Kingdom.
  • Institute of Cell & Molecular Biosciences, Newcastle University, Newcastle, United Kingdom.
  • MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
  • Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, United Kingdom; Wellcome Trust Sanger Institute, Human Genetics, Hinxton, Cambridge, United Kingdom.
  • Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
  • National Institute for Health and Welfare, Department of Chronic Disease Prevention, Helsinki, Finland; National Institute for Health and Welfare, Public Health Genomics Unit, Helsinki, Finland.
  • Istituto di Ricerca Genetica e Biomedica, CNR, Monserrato, Italy.
  • Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
  • National Cancer Institute, Bethesda, Maryland, United States of America.
  • Icelandic Heart Association, Kopavogur, Iceland; Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
  • Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Wellcome Trust Sanger Institute, Human Genetics, Hinxton, Cambridge, United Kingdom.
  • Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
  • deCODE Genetics, Amgen inc., Reykjavik, Iceland.
  • Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
  • Translational Gerontology Branch, National Institute on Aging, Baltimore, Maryland, United States of America.
  • Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands; Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
  • Estonian Genome Center, Univeristy of Tartu, Tartu, Estonia; National Institute for Health and Welfare, Public Health Genomics Unit, Helsinki, Finland; Institute of Cell and Molecular Biology, Department of Biotechnology, University of Tartu, Tartu, Estonia; University of Helsinki, Helsinki, Finland.
  • Department of Oncology, University of Cambridge, Cambridge, United Kingdom.
  • Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Internal Medicine, Section of Geriatric Medicine, Academic Medical Center, Amsterdam, The Netherlands.
  • Department of Medical Genetics, University Medical Center Utrecht, Utrecht, Netherlands.
  • University of Groningen, University Medical Center Groningen, Department of Endocrinology, Groningen, The Netherlands.
  • Transplantation Laboratory, Haartman Institute, University of Helsinki, Helsinki, Finland.
  • Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America; Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America; Division of Endocrinology, Boston Children's Hospital, Boston, Massachusetts, United States of America; Divisions of Genetics and Endocrinology and Program in Genomics, Boston's Children's Hospital, Boston, Massachusetts, United States of America.
  • Centre for Population Health Sciences, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland.
  • DZHK (German Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Lübeck, Germany; Institut für Integrative und Experimentelle Genomik, Universität zu Lübeck, Lübeck, Germany.
  • Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland.
  • MRC Unit for Lifelong Health & Ageing at UCL, London, United Kingdom.
  • Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia.
  • Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, United States of America.
  • Department of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom; Ealing Hospital NHS Trust, Middlesex, United Kingdom.
  • Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • University of Groningen, University Medical Center Groningen, Department of Medicine, Groningen, Netherlands.
  • Centro Cardiologico Monzino, IRCCS, Milan, Italy; Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Milan, Italy.
  • Department of Health Sciences, University of Milan, Milan, Italy.
  • Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas, United States of America; Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.
  • Department of Pediatrics, University of California San Diego, La Jolla, California, United States of America; Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland.
  • Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas, United States of America.
  • University of Leipzig, IFB Adiposity Diseases, Leipzig, Germany; University of Leipzig, Department of Medicine, Leipzig, Germany.
  • University Rennes 1, Rennes, France.
  • Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, United States of America.
  • University of Groningen, University Medical Center Groningen, The LifeLines Cohort Study, Groningen, The Netherlands.
  • Los Angeles BioMedical Resesarch Institute at Harbor-UCLA Medical Center, Torrance, California, United States of America.
  • Department of Internal Medicine I, Ulm University Medical Centre, Ulm, Germany.
  • VA Maryland Health Care System, Baltimore, Maryland, United States of America; Universiy of Maryland School of Medicine, Department of Neurology, Baltimore, Maryland, United States of America.
  • Department of Biological Psychology, VU University, Amsterdam, The Netherlands; EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
  • Department of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
  • Wellcome Trust Sanger Institute, Human Genetics, Hinxton, Cambridge, United Kingdom; Department of Dietetics-Nutrition, Harokopio University, Athens, Greece.
  • NorthShore University HealthSystem, Evanston, Illinois, United States of America; University of Chicago, Chicago, Illinois, United States of America.
  • Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece.
  • Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
  • Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Hypertension and Related Disease Centre, AOU-University of Sassari, Sassari, Italy.
  • Kaiser Permanente, Division of Research, Oakland, California, United States of America.
  • The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York, United States of America; The Department of Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
  • Department of Medicine III, Pathobiochemistry, University of Dresden, Dresden, Germany.
  • Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany.
  • Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
  • Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
  • Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.
  • Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, Maryland, United States of America; National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America.
  • University of Groningen, University Medical Center Groningen, Department of Psychiatry, Groningen, The Netherlands.
  • Kuopio Research Institute of Exercise Medicine, Kuopio, Finland.
  • MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, Scotland.
  • Institue of Biomedical & Clinical Science, University of Exeter, Exeter, United Kingdom.
  • QIMR Bergofer Medical Research Institute, Brisbane, Queensland, Australia.
  • Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America.
  • Department of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim, Norway.
  • Department Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
  • Pathwest Laboratory Medicine of Western Australia, Nedlands, Western Australia,Australia; School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands, Western Australia, Australia; School of Population Health, University of Western Australia, Nedlands, Western Australia, Australia.
  • Research Centre for Prevention and Health, Glostrup Hospital, Glostrup, Denmark.
  • Department of Pediatrics, University of Tampere School of Medicine, Tampere, Finland; Department of Pediatrics,Tampere University Hospital, Tampere, Finland.
  • Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; Hannover Unified Biobank, Hannover Medical School, Hannover, Germany; Institute of Human Genetics, Hannover Medical School, Hanover, Germany.
  • Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America; Harvard Medical School, Boston, Massachusetts,United States of America; Program in Translational NeuroPsychiatric Genomics, Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts,United States of America.
  • Research Centre for Prevention and Health, Glostrup Hospital, Glostrup, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Faculty of Medicine, University of Aalborg, Aalborg, Denmark.
  • Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands.
  • Division of Medicine, Turku University Hospital, Turku, Finland; Murdoch Children's Research Institute, Parkville, Victoria, Australia; Department of Medicine, University of Turku, Turku, Finland.
  • Wellcome Trust Sanger Institute, Human Genetics, Hinxton, Cambridge, United Kingdom; William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
  • Echinos Medical Centre, Echinos, Greece.
  • Clinical Gerontology Unit, Addenbrooke's Hospital, Cambridge, United Kingdom.
  • Department of Health, National Institute for Health and Welfare, Helsinki, Finland.
  • Department of Internal Medicine II-Cardiology, University of Ulm Medical Center, Ulm, Germany.
  • Department of Public Health, Faculty of Medicine, University of Split, Split, Croatia.
  • University of Leipzig, IFB Adiposity Diseases, Leipzig, Germany.
  • Department of Medicine A, University Medicine Greifswald, Greifswald, Germany.
  • Department of Epidemiology and Public Health, UCL, London, United Kingdom.
  • MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom; Department of Epidemiology and Public Health, UCL, London, United Kingdom.
  • Department of Public Health and Caring Sciences, Geriatrics, Uppsala University, Uppsala, Sweden.
  • Chair of Nephrology, Università Vita Salute San Raffaele, Segrate (Milan), Italy; Genomics of Renal Disease and Hypertension Unit, IRCCS San Raffaele Scientific Institute, Segrate (Milan), Italy.
  • Department of Biological Sciences, University of Calgary, Calgary, Alberta, Canada.
  • National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America.
  • Diabetes Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland.
  • Research Centre for Prevention and Health, Glostrup Hospital, Glostrup, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Experimental Research, Rigshospitalet, Glostrup, Denmark.
  • Strangeways Research Laboratory Wort's Causeway, Cambridge, United Kingdom.
  • Steno Diabetes Center A/S, Gentofte, Denmark; Lund University Diabetes Centre and Department of Clinical Science, Diabetes & Endocrinology Unit, Lund University, Malmö, Sweden.
  • National Institute for Health and Welfare, Department of Chronic Disease Prevention, Helsinki, Finland.
  • Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
  • Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Department of Biostatistics, University of Liverpool, Liverpool, United Kingdom.
  • MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom; MRC Unit for Lifelong Health & Ageing at UCL, London, United Kingdom; Department of Paediatrics, University of Cambridge, Cambridge, United Kingdom.
  • Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland; Wellcome Trust Sanger Institute, Human Genetics, Hinxton, Cambridge, United Kingdom; Massachusetts General Hospital, Center for Human Genetic Research, Psychiatric and Neurodevelopmental Genetics Unit, Boston, Massachusetts, United States of America.
  • Department of Kinesiology, Laval University, Québec City, Québec, Canada; Institute of Nutrition and Functional Foods, Laval University, Québec City, Québec, Canada.
  • Center for Biomedicine, European Academy Bozen/Bolzano (EURAC), Bolzano, Italy, Affiliated Institute of the University of Lübeck, Lübeck, Germany.
  • Department of Children, Young People and Families, National Institute for Health and Welfare, Helsinki, Finland; Department of Obstetrics and Gynecology, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.
  • Department of Nephrology, University Hospital Regensburg, Regensburg, Germany.
  • Department of Biostatistics, University of Washington, Seattle, Washington, United States of America.
  • Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri, United States of America; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, United States of America.
  • Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland.
  • Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana, United States of America.
  • Institute of Health Sciences, University of Oulu, Oulu, Finland.
  • Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden; Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden.
  • Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
  • Science for Life Laboratory, Uppsala University, Uppsala, Sweden; Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
  • Ealing Hospital NHS Trust, Middlesex, United Kingdom; National Heart and Lung Institute, Imperial College London, London, United Kingdom.
  • Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany.
  • University of Leipzig, Department of Medicine, Leipzig, Germany.
  • Department of Kinesiology, Laval University, Québec City, Québec, Canada.
  • Anogia Medical Centre, Anogia, Greece.
  • Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany; DZHK (German Centre for Cardiovascular Research), partner site Greifswald, Greifswald, Germany.
  • Institute of Nutrition and Functional Foods, Laval University, Québec City, Québec, Canada; School of Nutrition, Laval University, Québec City, Québec,Canada.
  • DZHK (German Centre for Cardiovascular Research), partnersite Munich Heart Alliance, Munich, Germany; Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
  • Department of Clinical Chemistry, Ulm University Medical Centre, Ulm, Germany.
  • Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
  • Department of Clinical Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway; Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway.
  • Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), The Netherlands; Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
  • EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands; VUMC, Department of Epidemiology and Biostatistics, Amsterdam, The Netherlands.
  • Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht, Netherlands; Durrer Center for Cardiogenetic Research, Interuniversity Cardiology Institute Netherlands-Netherlands Heart Institute, Utrecht, The Netherlands; Institute of Cardiovascular Science, University College London, London, United Kingdom.
  • Department of Medical Genetics, University Medical Center Utrecht, Utrecht, Netherlands; Department of Epidemiology, University Medical Center, Utrecht, The Netherlands.
  • Swiss Institute of Bioinformatics, Lausanne, Switzerland.
  • Pathwest Laboratory Medicine of Western Australia, Nedlands, Western Australia,Australia; School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands, Western Australia, Australia.
  • Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
  • Swiss Institute of Bioinformatics, Lausanne, Switzerland; Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland.
  • Department of Internal Medicine I, Ulm University Medical Centre, Ulm, Germany; Imperial College London, London, United Kingdom; Lee Kong Chian School of Medicine, Singapore, Singapore; Nanyang Technological University, Singapore, Singapore.
  • Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Science Center, Houston, Texas, United States of America.
  • Department of Medicine III, University of Dresden, Medical Faculty Carl Gustav Carus, Dresden, Germany.
  • Department of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom; Ealing Hospital NHS Trust, Middlesex, United Kingdom; Imperial College Healthcare NHS Trust, London, United Kingdom.
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America; Program in Biostatistics and Biomathematics, Divison of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
  • Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States of America; Harvard Medical School, Boston, Massachusetts,United States of America.
  • Istituto di Ricerca Genetica e Biomedica, CNR, Monserrato, Italy; University of Sassari, Sassari, Italy.
  • Department of Health Sciences, University of Milan, Milan, Italy; Institute of Biomedical Technologies, National Institute of Research, Segrate-Milano, Italy.
  • National Institute for Health and Welfare, Department of Chronic Disease Prevention, Helsinki, Finland; Folkhälsan Research Centre, Helsinki, Finland; Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland.
  • Rush Institute for Healthy Aging and Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois, United States of America.
  • Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Division of Cardiovacular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom; Durrer Center for Cardiogenetic Research, Amsterdam, The Netherlands.
  • Robertson Center for Biostatistics, University of Glasgow, Glasgow, United Kingdom.
  • University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, Netherlands.
  • Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Skåne University Hospital Malmö, Malmö, Sweden; Department of Public Health & Clinical Medicine, Umeå University Hospital, Umeå, Sweden, Umeå, Sweden; Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, United States of America.
  • Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
  • Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
  • University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, Netherlands; Durrer Center for Cardiogenetic Research, Interuniversity Cardiology Institute Netherlands-Netherlands Heart Institute, Utrecht, The Netherlands.
  • DZHK (German Centre for Cardiovascular Research), partnersite Munich Heart Alliance, Munich, Germany; Deutsches Herzzentrum München, Technische Universität München, München, Germany.
  • Institute of Cardiovascular Science, University College London, London, United Kingdom.
  • Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), The Netherlands; Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
  • Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, United States of America; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
  • Medical Research Center Oulu, Oulu University Hospital, and University of Oulu, Oulu, Finland.
  • Department of Pulmonary Physiology and Sleep Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
  • Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland; Department of Clinical Physiology, University of Tampere School of Medicine, Tampere, Finland.
  • Diabetes Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland; Children's Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
  • Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America; Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts, United States of America; Center for Human Genetics Research, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
  • Radboud university medical center, Radboud Institute for Health Sciences, Department for Health Evidence, Nijmegen, The Netherlands; Radboud university medical center, Radboud Institute for Health Sciences, Department of Urology, Nijmegen, The Netherlands.
  • National Institute for Health and Welfare, Helsinki, Finland.
  • National Institute for Health and Welfare, Helsinki, Finland; University of Helsinki and Helsinki University Central Hospital, Department of Medicine and Abdominal Center: Endocrinology, Helsinki, Finland; Minerva Foundation Institute for Medical Research, Helsinki, Finland.
  • Ealing Hospital NHS Trust, Middlesex, United Kingdom; National Heart and Lung Institute, Imperial College London, London, United Kingdom; Imperial College Healthcare NHS Trust, London, United Kingdom.
  • Vth Department of Medicine, Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
  • Kuopio Research Institute of Exercise Medicine, Kuopio, Finland; Department of Physiology, Institute of Biomedicine, University of Eastern Finland, Kuopio Campus, Kuopio, Finland.
  • Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere, Finland; Department of Clinical Chemistry, Fimlab Laboratories and School of Medicine, University of Tampere, Tampere, Finland.
  • Montreal Heart Institute, Montréal, Québec, Canada; Department of Medicine, Université de Montréal, Montréal, Québec, Canada.
  • Stanford University, Stanford, California, United States of America.
  • Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
  • Primary Health Care Unit, Institute of Public Health and Clinical Nutrition, School of Medicine, University of Eastern Finland, Kuopio, Finland; Primary Health Care Unit, Kuopio University Hospital, Kuopio, Finland.
  • Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Medicine, Stanford University School of Medicine, Stanford, California, United States of America.
  • University of Maryland School of Medicine, Department of Medicine, Baltimore, Maryland, United States of America; Geriatrics Research and Education Clinical Center, Baltimore Veterans Administration Medical Center, Baltimore, Maryland, United States of America.
  • Department of Surgery, University Medical Center Utrecht, Utrecht, Netherlands.
  • Department of Pediatrics, University of Iowa, Iowa City, Iowa, United States of America.
  • Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
  • HUCH Heart and Lung Center, Division of Cardiology, Helsinki University Central Hospital, Helsinki, Finland.
  • University of Groningen, University Medical Center, Interdisciplinary Center Psychopathology and Emotion Regulation, Groningen, The Netherlands.
  • School of Public Health, University of Adelaide, Adelaide, South Australia, Australia; Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia.
  • Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, United States of America.
  • Estonian Genome Center, Univeristy of Tartu, Tartu, Estonia; National Institute for Health and Welfare, Department of Chronic Disease Prevention, Helsinki, Finland; Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
  • Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland; Department of Public Health, Faculty of Medicine, University of Split, Split, Croatia.
  • Center for Biomedicine, European Academy Bozen/Bolzano (EURAC), Bolzano, Italy, Affiliated Institute of the University of Lübeck, Lübeck, Germany; Department of Neurology, General Central Hospital, Bolzano, Italy.
  • Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, United States of America; Department of Medicine, University of Washington, Seattle, Washington, United States of America; Departments of Epidemiology and Health Services, University of Washington, Seattle, Washington, United States of America; Group Health Research Institute, Group Health Cooperative, Seatte, Washington, United States of America.
  • Department of Medicine, Stanford University School of Medicine, Stanford, California, United States of America.
  • Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland; Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
  • Kuopio Research Institute of Exercise Medicine, Kuopio, Finland; Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland.
  • Department of Medicine, Central Finland Central Hospital, Jyväskylä, Finland.
  • BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom.
  • Program for Personalized and Genomic Medicine, Division of Endocrinology, Diabetes & Nutrition, Dept of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, United States of America; Geriatric Research and Education Clinical Center, Vetrans Administration Medical Center, Baltimore, Maryland, United States of America.
  • Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom; Institute of Preventive Medicine, Bispebjerg and Frederiksberg Hospital, The Capital Region, Frederiksberg, Denmark.
  • Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium; R & D VitaK Group, Maastricht University, Maastricht, The Netherlands.
  • Geriatric Unit, Azienda Sanitaria Firenze (ASF), Florence, Italy.
  • deCODE Genetics, Amgen inc., Reykjavik, Iceland; Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
  • Diabetes Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland; Centre for Vascular Prevention, Danube-University Krems, Krems, Austria; Instituto de Investigacion Sanitaria del Hospital Universitario La Paz (IdiPAZ), Madrid, Spain; Diabetes Research Group, King Abdulaziz University, Jeddah, Saudi Arabia.
  • Department of Public Health and Clinical Nutrition, University of Eastern Finland, Finland; Research Unit, Kuopio University Hospital, Kuopio, Finland.
  • Radboud university medical center, Radboud Institute for Health Sciences, Department for Health Evidence, Nijmegen, The Netherlands; Department of Human Genetics, Radboud university medical center, Nijmegen, The Netherlands.
  • Department of Medicine, University of Turku, Turku, Finland.
  • Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany; DZHK (German Centre for Cardiovascular Research), partner site Greifswald, Greifswald, Germany.
  • Department of Internal Medicine, University Hospital Lausanne (CHUV) and University of Lausanne, Lausanne, Switzerland.
  • Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America; Institute of Cellular Medicine, Newcastle University, Newcastle, United Kingdom.
  • Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany; DZHK (German Centre for Cardiovascular Research), partner site Greifswald, Greifswald, Germany.
  • Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
  • National Heart, Lung, and Blood Institute, the Framingham Heart Study, Framingham, Massachusetts, United States of America; Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, United States of America.
  • Department of Nutrition, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, United States of America; Carolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
  • National Heart, Lung, and Blood Institute, National Institute of Health, Bethesda, Maryland, United States of America.
  • Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, United States of America; Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri, United States of America; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, United States of America.
  • Wellcome Trust Sanger Institute, Human Genetics, Hinxton, Cambridge, United Kingdom; NIHR Cambridge Biomedical Research Centre, Institute of Metabolic Science Addenbrooke's Hospital, Cambridge, United Kingdom; University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science Addenbrooke's Hospital, Cambridge, United Kingdom.
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
  • Wellcome Trust Sanger Institute, Human Genetics, Hinxton, Cambridge, United Kingdom; William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom; Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia.
  • National Heart, Lung, and Blood Institute, the Framingham Heart Study, Framingham, Massachusetts, United States of America; Harvard Medical School, Boston, Massachusetts,United States of America.
  • Lund University Diabetes Centre and Department of Clinical Science, Diabetes & Endocrinology Unit, Lund University, Malmö, Sweden; Finnish Institute for Molecular Medicine (FIMM), Helsinki University, Helsinki, Finland.
  • Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts, United States of America; Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, United States of America; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America; Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America.
  • Science for Life Laboratory, Uppsala University, Uppsala, Sweden; Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala, Sweden; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, United States of America.
  • Department of Epidemiology and Popualtion Health, Albert Einstein College of Medicine, Bronx, New York, United States of America.
  • Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, United Kingdom; Oxford NIHR Biomedical Research Centre, Oxford, United Kingdom.
  • Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, United States of America.
  • Population Health Research Institute, St George's, University of London, London, United Kingdom.
  • Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands; Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), The Netherlands; Center for Medical Systems Biology, Leiden, The Netherlands.
  • Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts, United States of America; Divisions of Endocrinology and Genetics and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts, United States of America; Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America.
  • Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts, United States of America; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
  • Department of Genetic Epidemiology, Institute of Epidemiology and Preventive Medicine, University Regensburg, Regensburg, Germany; Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
  • Carolina Center for Genome Sciences and Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
  • Swiss Institute of Bioinformatics, Lausanne, Switzerland; Institute of Social and Preventive Medicine, University Hospital Lausanne (CHUV), Lausanne, Switzerland; Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland.
  • MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom; The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York, United States of America; The Department of Preventive Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York, United States of America; The Genetics of Obesity and Related Metabolic Traits Program, The Icahn School of Medicine at Mount Sinai, New York, New York, United States of America; The Mindich Child Health and Development Institute, The Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
Abstract

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR<5%) age-specific effects, of which 11 had larger effects in younger (<50y) than in older adults (≥50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may provide further insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.

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