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PLoS Genet. 2015 Oct 1;11(10):e1005378. doi: 10.1371/journal.pgen.1005378. eCollection 2015 Oct.

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

Winkler TW1, Justice AE2, Graff M2, Barata L3, Feitosa MF3, Chu S4, Czajkowski J3, Esko T5, Fall T6, Kilpeläinen TO7, Lu Y8, Mägi R9, Mihailov E10, Pers TH11, Rüeger S12, Teumer A13, Ehret GB14, Ferreira T15, Heard-Costa NL16, Karjalainen J17, Lagou V18, Mahajan A15, Neinast MD19, Prokopenko I20, Simino J21, Teslovich TM4, Jansen R22, Westra HJ23, White CC24, Absher D25, Ahluwalia TS26, Ahmad S27, Albrecht E28, Alves AC29, Bragg-Gresham JL4, de Craen AJ30, Bis JC31, Bonnefond A32, Boucher G33, Cadby G34, Cheng YC35, Chiang CW36, Delgado G37, Demirkan A38, Dueker N39, Eklund N40, Eiriksdottir G41, Eriksson J42, Feenstra B43, Fischer K10, Frau F44, Galesloot TE45, Geller F43, Goel A46, Gorski M47, Grammer TB37, Gustafsson S6, Haitjema S48, Hottenga JJ49, Huffman JE50, Jackson AU4, Jacobs KB51, Johansson Å52, Kaakinen M53, Kleber ME37, Lahti J54, Mateo Leach I55, Lehne B56, Liu Y57, Lo KS33, Lorentzon M42, Luan J58, Madden PA59, Mangino M60, McKnight B61, Medina-Gomez C62, Monda KL63, Montasser ME64, Müller G65, Müller-Nurasyid M66, Nolte IM67, Panoutsopoulou K68, Pascoe L69, Paternoster L70, Rayner NW71, Renström F27, Rizzi F44, Rose LM72, Ryan KA64, Salo P73, Sanna S74, Scharnagl H75, Shi J76, Smith AV77, Southam L78, Stančáková A79, Steinthorsdottir V80, Strawbridge RJ81, Sung YJ21, Tachmazidou I68, Tanaka T82, Thorleifsson G80, Trompet S83, Pervjakova N84, Tyrer JP85, Vandenput L42, van der Laan SW48, van der Velde N86, van Setten J87, van Vliet-Ostaptchouk JV88, Verweij N55, Vlachopoulou E89, Waite LL25, Wang SR90, Wang Z51, Wild SH91, Willenborg C92, Wilson JF93, Wong A94, Yang J95, Yengo L32, Yerges-Armstrong LM64, Yu L96, Zhang W97, Zhao JH58, Andersson EA98, Bakker SJ99, Baldassarre D100, Banasik K98, Barcella M101, Barlassina C101, Bellis C102, Benaglio P103, Blangero J104, Blüher M105, Bonnet F106, Bonnycastle LL107, Boyd HA43, Bruinenberg M108, Buchman AS96, Campbell H93, Chen YD109, Chines PS107, Claudi-Boehm S110, Cole J111, Collins FS107, de Geus EJ112, de Groot LC113, Dimitriou M114, Duan J115, Enroth S52, Eury E32, Farmaki AE116, Forouhi NG58, Friedrich N117, Gejman PV115, Gigante B118, Glorioso N119, Go AS120, Gottesman O121, Gräßler J122, Grallert H123, Grarup N98, Gu YM124, Broer L125, Ham AC125, Hansen T126, Harris TB127, Hartman CA128, Hassinen M129, Hastie N130, Hattersley AT131, Heath AC59, Henders AK132, Hernandez D133, Hillege H55, Holmen O134, Hovingh KG135, Hui J136, Husemoen LL137, Hutri-Kähönen N138, Hysi PG60, Illig T139, De Jager PL140, Jalilzadeh S46, Jørgensen T141, Jukema JW142, Juonala M143, Kanoni S144, Karaleftheri M145, Khaw KT146, Kinnunen L147, Kittner SJ111, Koenig W148, Kolcic I149, Kovacs P150, Krarup NT98, Kratzer W110, Krüger J151, Kuh D94, Kumari M152, Kyriakou T46, Langenberg C153, Lannfelt L154, Lanzani C155, Lotay V156, Launer LJ157, Leander K118, Lindström J158, Linneberg A159, Liu YP124, Lobbens S32, Luben R160, Lyssenko V161, Männistö S162, Magnusson PK163, McArdle WL164, Menni C60, Merger S110, Milani L10, Montgomery GW132, Morris AP165, Narisu N107, Nelis M10, Ong KK166, Palotie A167, Pérusse L168, Pichler I169, Pilia MG74, Pouta A170, Rheinberger M171, Ribel-Madsen R98, Richards M94, Rice KM172, Rice TK173, Rivolta C174, Salomaa V162, Sanders AR115, Sarzynski MA175, Scholtens S67, Scott RA58, Scott WR97, Sebert S176, Sengupta S4, Sennblad B177, Seufferlein T110, Silveira A81, Slagboom PE178, Smit JH22, Sparsø TH98, Stirrups K144, Stolk RP67, Stringham HM4, Swertz MA17, Swift AJ107, Syvänen AC179, Tan ST180, Thorand B181, Tönjes A182, Tremblay A183, Tsafantakis E184, van der Most PJ67, Völker U185, Vohl MC186, Vonk JM67, Waldenberger M187, Walker RW8, Wennauer R188, Widén E189, Willemsen G49, Wilsgaard T190, Wright AF130, Zillikens MC191, van Dijk SC125, van Schoor NM192, Asselbergs FW193, de Bakker PI194, Beckmann JS195, Beilby J196, Bennett DA96, Bergman RN197, Bergmann S198, Böger CA171, Boehm BO199, Boerwinkle E200, Boomsma DI49, Bornstein SR201, Bottinger EP121, Bouchard C175, Chambers JC202, Chanock SJ203, Chasman DI204, Cucca F205, Cusi D206, Dedoussis G116, Erdmann J92, Eriksson JG207, Evans DA208, de Faire U118, Farrall M209, Ferrucci L82, Ford I210, Franke L211, Franks PW212, Froguel P32, Gansevoort RT99, Gieger C213, Grönberg H163, Gudnason V77, Gyllensten U52, Hall P163, Hamsten A214, van der Harst P215, Hayward C130, Heliövaara M147, Hengstenberg C216, Hicks AA169, Hingorani A217, Hofman A218, Hu F219, Huikuri HV220, Hveem K134, James AL221, Jordan JM57, Jula A162, Kähönen M222, Kajantie E223, Kathiresan S224, Kiemeney LA225, Kivimaki M152, Knekt PB226, Koistinen HA227, Kooner JS228, Koskinen S147, Kuusisto J79, Maerz W229, Martin NG132, Laakso M79, Lakka TA230, Lehtimäki T231, Lettre G232, Levinson DF233, Lind L234, Lokki ML89, Mäntyselkä P235, Melbye M236, Metspalu A10, Mitchell BD237, Moll FL238, Murray JC239, Musk AW240, Nieminen MS241, Njølstad I190, Ohlsson C42, Oldehinkel AJ242, Oostra BA38, Palmer LJ243, Pankow JS244, Pasterkamp G48, Pedersen NL163, Pedersen O98, Penninx BW22, Perola M245, Peters A187, Polašek O246, Pramstaller PP247, Psaty BM248, Qi L219, Quertermous T249, Raitakari OT250, Rankinen T175, Rauramaa R251, Ridker PM204, Rioux JD232, Rivadeneira F62, Rotter JI109, Rudan I93, den Ruijter HM48, Saltevo J252, Sattar N253, Schunkert H216, Schwarz PE201, Shuldiner AR254, Sinisalo J241, Snieder H67, Sørensen TI255, Spector TD60, Staessen JA256, Stefania B257, Thorsteinsdottir U258, Stumvoll M105, Tardif JC232, Tremoli E100, Tuomilehto J259, Uitterlinden AG62, Uusitupa M260, Verbeek AL45, Vermeulen SH261, Viikari JS262, Vitart V130, Völzke H263, Vollenweider P264, Waeber G264, Walker M265, Wallaschofski H266, Wareham NJ58, Watkins H46, Zeggini E68; CHARGE Consortium; DIAGRAM Consortium; GLGC Consortium; Global-BPGen Consortium; ICBP Consortium; MAGIC Consortium, Chakravarti A267, Clegg DJ19, Cupples LA268, Gordon-Larsen P269, Jaquish CE270, Rao DC271, Abecasis GR4, Assimes TL249, Barroso I272, Berndt SI273, Boehnke M4, Deloukas P274, Fox CS275, Groop LC276, Hunter DJ277, Ingelsson E278, Kaplan RC279, McCarthy MI280, Mohlke KL281, O'Connell JR64, Schlessinger D157, Strachan DP282, Stefansson K258, van Duijn CM283, Hirschhorn JN284, Lindgren CM285, Heid IM286, North KE287, Borecki IB3, Kutalik Z288, Loos RJ289.

Author information

1
Department of Genetic Epidemiology, Institute of Epidemiology and Preventive Medicine, University Regensburg, Regensburg, Germany.
2
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
3
Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, United States of America.
4
Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, United States of America.
5
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.
6
Science for Life Laboratory, Uppsala University, Uppsala, Sweden; Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala, Sweden.
7
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.
8
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.
9
Estonian Genome Center, Univeristy of Tartu, Tartu, Estonia; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
10
Estonian Genome Center, Univeristy of Tartu, Tartu, Estonia.
11
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.
12
Swiss Institute of Bioinformatics, Lausanne, Switzerland; Institute of Social and Preventive Medicine, University Hospital Lausanne (CHUV), Lausanne, Switzerland.
13
Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany; Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
14
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.
15
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
16
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.
17
University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands.
18
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.
19
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
20
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.
21
Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri, United States of America.
22
Department of Psychiatry and EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, the Netherlands.
23
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.
24
Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, United States of America.
25
HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, United States of America.
26
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.
27
Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Skåne University Hospital Malmö, Malmö, Sweden.
28
Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
29
Department of Epidemiology and Biostatistics, MRC Health Protection Agency (HPA) Centre for Environment and Health, School of Public Health, Imperial College, London, United Kingdom.
30
Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.
31
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.
32
CNRS UMR 8199, Lille, France; European Genomic Institute for Diabetes, Lille, France; Université de Lille 2, Lille, France.
33
Montreal Heart Institute, Montréal, Québec, Canada.
34
Centre for Genetic Origins of Health and Disease, University of Western Australia, Crawley, Western Australia, Australia.
35
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.
36
Department of Ecology and Evolutionary Biology, University of California, Los Angeles, Los Angeles, California, United States of America.
37
Vth Department of Medicine, Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany.
38
Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
39
Universiy of Maryland School of Medicine, Department of Epidemiology & Public Health, Baltimore, Maryland, United States of America.
40
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.
41
Icelandic Heart Association, Kopavogur, Iceland.
42
Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
43
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
44
Department of Health Sciences, University of Milan, Milan, Italy; Filarete Foundation, Genomic and Bioinformatics Unit, Milano, Italy.
45
Radboud university medical center, Radboud Institute for Health Sciences, Department for Health Evidence, Nijmegen, The Netherlands.
46
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.
47
Department of Genetic Epidemiology, Institute of Epidemiology and Preventive Medicine, University Regensburg, Regensburg, Germany; Department of Nephrology, University Hospital Regensburg, Regensburg, Germany.
48
Experimental Cardiology and laboratory of clinical chemistry, UMCU, Utrecht, The Netherlands.
49
Department of Biological Psychology, VU University, Amsterdam, The Netherlands.
50
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.
51
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.
52
Science for Life Laboratory, Uppsala University, Uppsala, Sweden; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
53
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.
54
Folkhälsan Research Centre, Helsinki, Finland; Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.
55
University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, Netherlands.
56
Department of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom.
57
Thurston Arthritis Research Center, University of North Carolina at Chapel Hill, Chaper Hill, North Carolina, United States of America.
58
MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom.
59
Washington University Medical School, St. Louis, Missouri, United States of America.
60
Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom.
61
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.
62
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.
63
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.
64
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.
65
Center for Evidence Based Healthcare, University of Dresden, Medical Faculty Carl Gustav Carus, Dresden, Germany.
66
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.
67
University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, The Netherlands.
68
Wellcome Trust Sanger Institute, Human Genetics, Hinxton, Cambridge, United Kingdom.
69
Institute of Cell & Molecular Biosciences, Newcastle University, Newcastle, United Kingdom.
70
MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
71
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.
72
Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
73
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.
74
Istituto di Ricerca Genetica e Biomedica, CNR, Monserrato, Italy.
75
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
76
National Cancer Institute, Bethesda, Maryland, United States of America.
77
Icelandic Heart Association, Kopavogur, Iceland; Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
78
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Wellcome Trust Sanger Institute, Human Genetics, Hinxton, Cambridge, United Kingdom.
79
Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
80
deCODE Genetics, Amgen inc., Reykjavik, Iceland.
81
Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
82
Translational Gerontology Branch, National Institute on Aging, Baltimore, Maryland, United States of America.
83
Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands; Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
84
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.
85
Department of Oncology, University of Cambridge, Cambridge, United Kingdom.
86
Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Internal Medicine, Section of Geriatric Medicine, Academic Medical Center, Amsterdam, The Netherlands.
87
Department of Medical Genetics, University Medical Center Utrecht, Utrecht, Netherlands.
88
University of Groningen, University Medical Center Groningen, Department of Endocrinology, Groningen, The Netherlands.
89
Transplantation Laboratory, Haartman Institute, University of Helsinki, Helsinki, Finland.
90
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.
91
Centre for Population Health Sciences, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland.
92
DZHK (German Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Lübeck, Germany; Institut für Integrative und Experimentelle Genomik, Universität zu Lübeck, Lübeck, Germany.
93
Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland.
94
MRC Unit for Lifelong Health & Ageing at UCL, London, United Kingdom.
95
Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia.
96
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, United States of America.
97
Department of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom; Ealing Hospital NHS Trust, Middlesex, United Kingdom.
98
Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
99
University of Groningen, University Medical Center Groningen, Department of Medicine, Groningen, Netherlands.
100
Centro Cardiologico Monzino, IRCCS, Milan, Italy; Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Milan, Italy.
101
Department of Health Sciences, University of Milan, Milan, Italy.
102
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.
103
Department of Pediatrics, University of California San Diego, La Jolla, California, United States of America; Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland.
104
Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas, United States of America.
105
University of Leipzig, IFB Adiposity Diseases, Leipzig, Germany; University of Leipzig, Department of Medicine, Leipzig, Germany.
106
University Rennes 1, Rennes, France.
107
Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, United States of America.
108
University of Groningen, University Medical Center Groningen, The LifeLines Cohort Study, Groningen, The Netherlands.
109
Los Angeles BioMedical Resesarch Institute at Harbor-UCLA Medical Center, Torrance, California, United States of America.
110
Department of Internal Medicine I, Ulm University Medical Centre, Ulm, Germany.
111
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.
112
Department of Biological Psychology, VU University, Amsterdam, The Netherlands; EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
113
Department of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
114
Wellcome Trust Sanger Institute, Human Genetics, Hinxton, Cambridge, United Kingdom; Department of Dietetics-Nutrition, Harokopio University, Athens, Greece.
115
NorthShore University HealthSystem, Evanston, Illinois, United States of America; University of Chicago, Chicago, Illinois, United States of America.
116
Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece.
117
Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
118
Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
119
Hypertension and Related Disease Centre, AOU-University of Sassari, Sassari, Italy.
120
Kaiser Permanente, Division of Research, Oakland, California, United States of America.
121
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.
122
Department of Medicine III, Pathobiochemistry, University of Dresden, Dresden, Germany.
123
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.
124
Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
125
Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
126
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.
127
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.
128
University of Groningen, University Medical Center Groningen, Department of Psychiatry, Groningen, The Netherlands.
129
Kuopio Research Institute of Exercise Medicine, Kuopio, Finland.
130
MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, Scotland.
131
Institue of Biomedical & Clinical Science, University of Exeter, Exeter, United Kingdom.
132
QIMR Bergofer Medical Research Institute, Brisbane, Queensland, Australia.
133
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America.
134
Department of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim, Norway.
135
Department Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
136
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.
137
Research Centre for Prevention and Health, Glostrup Hospital, Glostrup, Denmark.
138
Department of Pediatrics, University of Tampere School of Medicine, Tampere, Finland; Department of Pediatrics,Tampere University Hospital, Tampere, Finland.
139
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.
140
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.
141
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.
142
Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands.
143
Division of Medicine, Turku University Hospital, Turku, Finland; Murdoch Children's Research Institute, Parkville, Victoria, Australia; Department of Medicine, University of Turku, Turku, Finland.
144
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.
145
Echinos Medical Centre, Echinos, Greece.
146
Clinical Gerontology Unit, Addenbrooke's Hospital, Cambridge, United Kingdom.
147
Department of Health, National Institute for Health and Welfare, Helsinki, Finland.
148
Department of Internal Medicine II-Cardiology, University of Ulm Medical Center, Ulm, Germany.
149
Department of Public Health, Faculty of Medicine, University of Split, Split, Croatia.
150
University of Leipzig, IFB Adiposity Diseases, Leipzig, Germany.
151
Department of Medicine A, University Medicine Greifswald, Greifswald, Germany.
152
Department of Epidemiology and Public Health, UCL, London, United Kingdom.
153
MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom; Department of Epidemiology and Public Health, UCL, London, United Kingdom.
154
Department of Public Health and Caring Sciences, Geriatrics, Uppsala University, Uppsala, Sweden.
155
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.
156
Department of Biological Sciences, University of Calgary, Calgary, Alberta, Canada.
157
National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America.
158
Diabetes Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland.
159
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.
160
Strangeways Research Laboratory Wort's Causeway, Cambridge, United Kingdom.
161
Steno Diabetes Center A/S, Gentofte, Denmark; Lund University Diabetes Centre and Department of Clinical Science, Diabetes & Endocrinology Unit, Lund University, Malmö, Sweden.
162
National Institute for Health and Welfare, Department of Chronic Disease Prevention, Helsinki, Finland.
163
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
164
School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
165
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Department of Biostatistics, University of Liverpool, Liverpool, United Kingdom.
166
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.
167
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.
168
Department of Kinesiology, Laval University, Québec City, Québec, Canada; Institute of Nutrition and Functional Foods, Laval University, Québec City, Québec, Canada.
169
Center for Biomedicine, European Academy Bozen/Bolzano (EURAC), Bolzano, Italy, Affiliated Institute of the University of Lübeck, Lübeck, Germany.
170
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.
171
Department of Nephrology, University Hospital Regensburg, Regensburg, Germany.
172
Department of Biostatistics, University of Washington, Seattle, Washington, United States of America.
173
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.
174
Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland.
175
Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana, United States of America.
176
Institute of Health Sciences, University of Oulu, Oulu, Finland.
177
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.
178
Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
179
Science for Life Laboratory, Uppsala University, Uppsala, Sweden; Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
180
Ealing Hospital NHS Trust, Middlesex, United Kingdom; National Heart and Lung Institute, Imperial College London, London, United Kingdom.
181
Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany.
182
University of Leipzig, Department of Medicine, Leipzig, Germany.
183
Department of Kinesiology, Laval University, Québec City, Québec, Canada.
184
Anogia Medical Centre, Anogia, Greece.
185
Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany; DZHK (German Centre for Cardiovascular Research), partner site Greifswald, Greifswald, Germany.
186
Institute of Nutrition and Functional Foods, Laval University, Québec City, Québec, Canada; School of Nutrition, Laval University, Québec City, Québec,Canada.
187
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.
188
Department of Clinical Chemistry, Ulm University Medical Centre, Ulm, Germany.
189
Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
190
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.
191
Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), The Netherlands; Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
192
EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands; VUMC, Department of Epidemiology and Biostatistics, Amsterdam, The Netherlands.
193
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.
194
Department of Medical Genetics, University Medical Center Utrecht, Utrecht, Netherlands; Department of Epidemiology, University Medical Center, Utrecht, The Netherlands.
195
Swiss Institute of Bioinformatics, Lausanne, Switzerland.
196
Pathwest Laboratory Medicine of Western Australia, Nedlands, Western Australia,Australia; School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands, Western Australia, Australia.
197
Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
198
Swiss Institute of Bioinformatics, Lausanne, Switzerland; Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland.
199
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.
200
Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Science Center, Houston, Texas, United States of America.
201
Department of Medicine III, University of Dresden, Medical Faculty Carl Gustav Carus, Dresden, Germany.
202
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.
203
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.
204
Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States of America; Harvard Medical School, Boston, Massachusetts,United States of America.
205
Istituto di Ricerca Genetica e Biomedica, CNR, Monserrato, Italy; University of Sassari, Sassari, Italy.
206
Department of Health Sciences, University of Milan, Milan, Italy; Institute of Biomedical Technologies, National Institute of Research, Segrate-Milano, Italy.
207
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.
208
Rush Institute for Healthy Aging and Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois, United States of America.
209
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.
210
Robertson Center for Biostatistics, University of Glasgow, Glasgow, United Kingdom.
211
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.
212
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.
213
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.
214
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.
215
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.
216
DZHK (German Centre for Cardiovascular Research), partnersite Munich Heart Alliance, Munich, Germany; Deutsches Herzzentrum München, Technische Universität München, München, Germany.
217
Institute of Cardiovascular Science, University College London, London, United Kingdom.
218
Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), The Netherlands; Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
219
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.
220
Medical Research Center Oulu, Oulu University Hospital, and University of Oulu, Oulu, Finland.
221
Department of Pulmonary Physiology and Sleep Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
222
Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland; Department of Clinical Physiology, University of Tampere School of Medicine, Tampere, Finland.
223
Diabetes Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland; Children's Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
224
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.
225
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.
226
National Institute for Health and Welfare, Helsinki, Finland.
227
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.
228
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.
229
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.
230
Kuopio Research Institute of Exercise Medicine, Kuopio, Finland; Department of Physiology, Institute of Biomedicine, University of Eastern Finland, Kuopio Campus, Kuopio, Finland.
231
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.
232
Montreal Heart Institute, Montréal, Québec, Canada; Department of Medicine, Université de Montréal, Montréal, Québec, Canada.
233
Stanford University, Stanford, California, United States of America.
234
Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
235
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.
236
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.
237
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.
238
Department of Surgery, University Medical Center Utrecht, Utrecht, Netherlands.
239
Department of Pediatrics, University of Iowa, Iowa City, Iowa, United States of America.
240
Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
241
HUCH Heart and Lung Center, Division of Cardiology, Helsinki University Central Hospital, Helsinki, Finland.
242
University of Groningen, University Medical Center, Interdisciplinary Center Psychopathology and Emotion Regulation, Groningen, The Netherlands.
243
School of Public Health, University of Adelaide, Adelaide, South Australia, Australia; Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia.
244
Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, United States of America.
245
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.
246
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.
247
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.
248
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.
249
Department of Medicine, Stanford University School of Medicine, Stanford, California, United States of America.
250
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.
251
Kuopio Research Institute of Exercise Medicine, Kuopio, Finland; Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland.
252
Department of Medicine, Central Finland Central Hospital, Jyväskylä, Finland.
253
BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom.
254
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.
255
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.
256
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.
257
Geriatric Unit, Azienda Sanitaria Firenze (ASF), Florence, Italy.
258
deCODE Genetics, Amgen inc., Reykjavik, Iceland; Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
259
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.
260
Department of Public Health and Clinical Nutrition, University of Eastern Finland, Finland; Research Unit, Kuopio University Hospital, Kuopio, Finland.
261
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.
262
Department of Medicine, University of Turku, Turku, Finland.
263
Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany; DZHK (German Centre for Cardiovascular Research), partner site Greifswald, Greifswald, Germany.
264
Department of Internal Medicine, University Hospital Lausanne (CHUV) and University of Lausanne, Lausanne, Switzerland.
265
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.
266
Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany; DZHK (German Centre for Cardiovascular Research), partner site Greifswald, Greifswald, Germany.
267
Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
268
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.
269
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.
270
National Heart, Lung, and Blood Institute, National Institute of Health, Bethesda, Maryland, United States of America.
271
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.
272
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.
273
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
274
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.
275
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.
276
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.
277
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.
278
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.
279
Department of Epidemiology and Popualtion Health, Albert Einstein College of Medicine, Bronx, New York, United States of America.
280
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.
281
Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, United States of America.
282
Population Health Research Institute, St George's, University of London, London, United Kingdom.
283
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.
284
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.
285
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.
286
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.
287
Carolina Center for Genome Sciences and Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
288
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.
289
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.

PMID:
26426971
PMCID:
PMC4591371
DOI:
10.1371/journal.pgen.1005378
[Indexed for MEDLINE]
Free PMC Article

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