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Nature. 2015 Feb 12;518(7538):197-206. doi: 10.1038/nature14177.

Genetic studies of body mass index yield new insights for obesity biology.

Locke AE#1, Kahali B#2, Berndt SI#3, Justice AE#4, Pers TH#5,6,7,8, Day FR9, Powell C2, Vedantam S5,6, Buchkovich ML10, Yang J11,12, Croteau-Chonka DC10,13, Esko T5,6,7,14, Fall T15,16,17, Ferreira T18, Gustafsson S16,17, Kutalik Z19,20,21, Luan J9, Mägi R14,18, Randall JC18,22, Winkler TW23, Wood AR24, Workalemahu T25, Faul JD26, Smith JA27, Zhao JH9, Zhao W27, Chen J28, Fehrmann R29, Hedman ÅK16,17,18, Karjalainen J29, Schmidt EM30, Absher D31, Amin N32, Anderson D33, Beekman M34,35, Bolton JL36, Bragg-Gresham JL1,37, Buyske S38,39, Demirkan A32,40, Deng G41,42,43, Ehret GB44,45, Feenstra B46, Feitosa MF47, Fischer K14, Goel A18,48, Gong J49, Jackson AU1, Kanoni S50, Kleber ME51,52, Kristiansson K53, Lim U54, Lotay V55, Mangino M56, Leach IM57, Medina-Gomez C58,59,60, Medland SE61, Nalls MA62, Palmer CD5,6, Pasko D24, Pechlivanis S63, Peters MJ58,60, Prokopenko I18,64,65, Shungin D66,67,68, Stančáková A69, Strawbridge RJ70, Sung YJ71, Tanaka T72, Teumer A73, Trompet S74,75, van der Laan SW76, van Setten J77, Van Vliet-Ostaptchouk JV78, Wang Z3,79, Yengo L80,81,82, Zhang W41,83, Isaacs A32,84, Albrecht E85, Ärnlöv J16,17,86, Arscott GM87, Attwood AP88,89, Bandinelli S90, Barrett A64, Bas IN91, Bellis C92,93, Bennett AJ64, Berne C94, Blagieva R95, Blüher M96,97, Böhringer S34,98, Bonnycastle LL99, Böttcher Y96, Boyd HA46, Bruinenberg M100, Caspersen IH101, Chen YI102,103, Clarke R104, Daw EW47, de Craen AJM75, Delgado G51, Dimitriou M105, Doney ASF106, Eklund N53,107, Estrada K6,60,108, Eury E80,81,82, Folkersen L70, Fraser RM36, Garcia ME109, Geller F46, Giedraitis V110, Gigante B111, Go AS112, Golay A113, Goodall AH114,115, Gordon SD61, Gorski M23,116, Grabe HJ117,118, Grallert H85,119,120, Grammer TB51, Gräßler J121, Grönberg H15, Groves CJ64, Gusto G122, Haessler J49, Hall P15, Haller T14, Hallmans G123, Hartman CA124, Hassinen M125, Hayward C126, Heard-Costa NL127,128, Helmer Q34,98,129, Hengstenberg C130,131, Holmen O132, Hottenga JJ133, James AL134,135, Jeff JM55, Johansson Å136, Jolley J88,89, Juliusdottir T18, Kinnunen L53, Koenig W52, Koskenvuo M137, Kratzer W138, Laitinen J139, Lamina C140, Leander K111, Lee NR91, Lichtner P141, Lind L142, Lindström J53, Lo KS143, Lobbens S80,81,82, Lorbeer R144, Lu Y55,145, Mach F45, Magnusson PKE15, Mahajan A18, McArdle WL146, McLachlan S36, Menni C56, Merger S95, Mihailov E14,147, Milani L14, Moayyeri A56,148, Monda KL4,149, Morken MA99, Mulas A150, Müller G151, Müller-Nurasyid M85,130,152,153, Musk AW154, Nagaraja R155, Nöthen MM156,157, Nolte IM158, Pilz S159,160, Rayner NW18,22,64, Renstrom F66, Rettig R161, Ried JS85, Ripke S108,162, Robertson NR18,64, Rose LM163, Sanna S150, Scharnagl H164, Scholtens S100, Schumacher FR165, Scott WR41,83, Seufferlein T138, Shi J166, Smith AV167,168, Smolonska J29,158, Stanton AV169, Steinthorsdottir V170, Stirrups K22,50, Stringham HM1, Sundström J142, Swertz MA29, Swift AJ99, Syvänen AC16,171, Tan ST41,172, Tayo BO173, Thorand B120,174, Thorleifsson G170, Tyrer JP175, Uh HW34,98, Vandenput L176, Verhulst FC177, Vermeulen SH178,179, Verweij N57, Vonk JM158, Waite LL31, Warren HR180, Waterworth D181, Weedon MN24, Wilkens LR54, Willenborg C182,183, Wilsgaard T184, Wojczynski MK47, Wong A185, Wright AF126, Zhang Q47; 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Author information

1
Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109, USA.
2
Department of Internal Medicine, Division of Gastroenterology, and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109, USA.
3
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
4
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
5
Divisions of Endocrinology and Genetics and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts 02115, USA.
6
Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA.
7
Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
8
Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby 2800, Denmark.
9
MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
10
Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
11
Queensland Brain Institute, The University of Queensland, Brisbane 4072, Australia.
12
The University of Queensland Diamantina Institute, The Translation Research Institute, Brisbane 4012, Australia.
13
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
14
Estonian Genome Center, University of Tartu, Tartu 51010, Estonia.
15
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 17177, Sweden.
16
Science for Life Laboratory, Uppsala University, Uppsala 75185, Sweden.
17
Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala 75185, Sweden.
18
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
19
Institute of Social and Preventive Medicine (IUMSP), Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne 1010, Switzerland.
20
Swiss Institute of Bioinformatics, Lausanne 1015, Switzerland.
21
Department of Medical Genetics, University of Lausanne, Lausanne 1005, Switzerland.
22
Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
23
Department of Genetic Epidemiology, Institute of Epidemiology and Preventive Medicine, University of Regensburg, D-93053 Regensburg, Germany.
24
Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter EX1 2LU, UK.
25
Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
26
Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, Michigan 48104, USA.
27
Department of Epidemiology, University of Michigan, Ann Arbor, Michigan 48109, USA.
28
Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
29
Department of Genetics, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
30
Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109, USA.
31
HudsonAlpha Institute for Biotechnology, Huntsville, Alabama 35806, USA.
32
Genetic Epidemiology Unit, Department of Epidemiology, Erasmus MC University Medical Center, 3015 GE Rotterdam, The Netherlands.
33
Telethon Institute for Child Health Research, Centre for Child Health Research, The University of Western Australia, Perth, Western Australia 6008, Australia.
34
Netherlands Consortium for Healthy Aging (NCHA), Leiden University Medical Center, Leiden 2300 RC, The Netherlands.
35
Department of Molecular Epidemiology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
36
Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, UK.
37
Kidney Epidemiology and Cost Center, University of Michigan, Ann Arbor, Michigan 48109, USA.
38
Department of Statistics & Biostatistics, Rutgers University, Piscataway, New Jersey 08854, USA.
39
Department of Genetics, Rutgers University, Piscataway, New Jersey 08854, USA.
40
Department of Human Genetics, Leiden University Medical Center, 2333 ZC Leiden, The Netherlands.
41
Ealing Hospital NHS Trust, Middlesex UB1 3HW, UK.
42
Department of Gastroenterology and Hepatology, Imperial College London, London W2 1PG, UK.
43
Institute of infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing, China.
44
Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
45
Cardiology, Department of Specialties of Internal Medicine, Geneva University Hospital, Geneva 1211, Switzerland.
46
Department of Epidemiology Research, Statens Serum Institut, Copenhagen DK-2300, Denmark.
47
Department of Genetics, Washington University School of Medicine, St Louis, Missouri 63110, USA.
48
Division of Cardiovacular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, UK.
49
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
50
William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.
51
Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty of Mannheim, University of Heidelberg, D-68187 Mannheim, Germany.
52
Department of Internal Medicine II, Ulm University Medical Centre, D-89081 Ulm, Germany.
53
National Institute for Health and Welfare, FI-00271 Helsinki, Finland.
54
Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii 96813, USA.
55
The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
56
Department of Twin Research and Genetic Epidemiology, King's College London, London SE1 7EH, UK.
57
Department of Cardiology, University Medical Center Groningen, University of Groningen, 9700RB Groningen, The Netherlands.
58
Netherlands Consortium for Healthy Aging (NCHA), 3015GE Rotterdam, The Netherlands.
59
Department of Epidemiology, Erasmus MC University Medical Center, 3015GE Rotterdam, The Netherlands.
60
Department of Internal Medicine, Erasmus MC University Medical Center, 3015GE Rotterdam, The Netherlands.
61
QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia.
62
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA.
63
Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University Hospital Essen, 45147 Essen, Germany.
64
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX3 7LJ, UK.
65
Department of Genomics of Common Disease, School of Public Health, Imperial College London, Hammersmith Hospital, London W12 0NN, UK.
66
Department of Clinical Sciences, Genetic & Molecular Epidemiology Unit, Lund University Diabetes Center, Skåne University Hosptial, Malmö 205 02, Sweden.
67
Department of Public Health and Clinical Medicine, Unit of Medicine, Umeå University, Umeå 901 87, Sweden.
68
Department of Odontology, Umeå University, Umeå 901 85, Sweden.
69
University of Eastern Finland, FI-70210 Kuopio, Finland.
70
Atherosclerosis Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm 17176, Sweden.
71
Division of Biostatistics, Washington University School of Medicine, St Louis, Missouri 63110, USA.
72
Translational Gerontology Branch, National Institute on Aging, Baltimore, Maryland 21225, USA.
73
Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, D-17475 Greifswald, Germany.
74
Department of Cardiology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
75
Department of Gerontology and Geriatrics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
76
Experimental Cardiology Laboratory, Division Heart and Lungs, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
77
Department of Medical Genetics, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
78
Department of Endocrinology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands.
79
Core Genotyping Facility, SAIC-Frederick, Inc., NCI-Frederick, Frederick, Maryland 21702, USA.
80
CNRS UMR 8199, F-59019 Lille, France.
81
European Genomic Institute for Diabetes, F-59000 Lille, France.
82
Université de Lille 2, F-59000 Lille, France.
83
Department of Epidemiology and Biostatistics, Imperial College London, London W2 1PG, UK.
84
Center for Medical Sytems Biology, 2300 RC Leiden, The Netherlands.
85
Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, D-85764 Neuherberg, Germany.
86
School of Health and Social Studies, Dalarna University, SE-791 88 Falun, Sweden.
87
PathWest Laboratory Medicine of Western Australia, Nedlands, Western Australia 6009, Australia.
88
Department of Haematology, University of Cambridge, Cambridge CB2 0PT, UK.
89
NHS Blood and Transplant, Cambridge CB2 0PT, UK.
90
Geriatric Unit, Azienda Sanitaria Firenze (ASF), 50125 Florence, Italy.
91
USC-Office of Population Studies Foundation, Inc., University of San Carlos, Cebu City 6000, Philippines.
92
Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas 78227, USA.
93
Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland 4001, Australia.
94
Department of Medical Sciences, Endocrinology, Diabetes and Metabolism, Uppsala University, Uppsala 75185, Sweden.
95
Division of Endocrinology, Diabetes and Metabolism, Ulm University Medical Centre, D-89081 Ulm, Germany.
96
Integrated Research and Treatment Center (IFB) Adiposity Diseases, University of Leipzig, D-04103 Leipzig, Germany.
97
Department of Medicine, University of Leipzig, D-04103 Leipzig, Germany.
98
Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
99
Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland 20892, USA.
100
LifeLines Cohort Study, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
101
Department of Biology, Norwegian University of Science and Technology, 7491 Trondheim, Norway.
102
Department of Pediatrics, University of California Los Angeles, Torrance, California 90502, USA.
103
Transgenomics Institute, Los Angeles Biomedical Research Institute, Torrance, California 90502, USA.
104
Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, UK.
105
Department of Dietetics-Nutrition, Harokopio University, 17671 Athens, Greece.
106
Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK.
107
Institute for Molecular Medicine, University of Helsinki, FI-00014 Helsinki, Finland.
108
Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
109
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIH, Bethesda, Maryland 20892, USA.
110
Department of Public Health and Caring Sciences, Geriatrics, Uppsala University, Uppsala 75185, Sweden.
111
Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, Stockholm 17177, Sweden.
112
Kaiser Permanente, Division of Research, Oakland, California 94612, USA.
113
Service of Therapeutic Education for Diabetes, Obesity and Chronic Diseases, Geneva University Hospital, Geneva CH-1211, Switzerland.
114
Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester LE3 9QP, UK.
115
National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester LE3 9QP, UK.
116
Department of Nephrology, University Hospital Regensburg, D-93053 Regensburg, Germany.
117
Department of Psychiatry and Psychotherapy, University Medicine Greifswald, HELIOS-Hospital Stralsund, D-17475 Greifswald, Germany.
118
German Center for Neurodegenerative Diseases (DZNE), Rostock, Greifswald, D-17475 Greifswald, Germany.
119
Research Unit of Molecular Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, D-85764 Neuherberg, Germany.
120
German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany.
121
Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, D-01307 Dresden, Germany.
122
Institut inter Régional pour la Santé, Synergies, F-37520 La Riche, France.
123
Department of Public Health and Clinical Medicine, Unit of Nutritional Research, Umeå University, Umeå 90187, Sweden.
124
Department of Psychiatry, University of Groningen, University Medical Center Groningen, 9700RB Groningen, The Netherlands.
125
Kuopio Research Institute of Exercise Medicine, 70100 Kuopio, Finland.
126
MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK.
127
National Heart, Lung, and Blood Institute, the Framingham Heart Study, Framingham, Massachusetts 01702, USA.
128
Department of Neurology, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
129
Faculty of Psychology and Education, VU University Amsterdam, 1081BT Amsterdam, The Netherlands.
130
Deutsches Forschungszentrum für Herz-Kreislauferkrankungen (DZHK) (German Research Centre for Cardiovascular Research), Munich Heart Alliance, D-80636 Munich, Germany.
131
Deutsches Herzzentrum München, Technische Universität München, D-80636 Munich, Germany.
132
Department of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim 7489, Norway.
133
Biological Psychology, VU University Amsterdam, 1081BT Amsterdam, The Netherlands.
134
Department of Pulmonary Physiology and Sleep Medicine, Nedlands, Western Australia 6009, Australia.
135
School of Medicine and Pharmacology, University of Western Australia, Crawley 6009, Australia.
136
Uppsala University, Department of Immunology, Genetics, Pathology, SciLifeLab, Rudbeck Laboratory, SE-751 85 Uppsala, Sweden.
137
Hjelt Institute Department of Public Health, University of Helsinki, FI-00014 Helsinki, Finland.
138
Department of Internal Medicine I, Ulm University Medical Centre, D-89081 Ulm, Germany.
139
Finnish Institute of Occupational Health, FI-90100 Oulu, Finland.
140
Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, 6020 Innsbruck, Austria.
141
Institute of Human Genetics, Helmholtz Zentrum München - German Research Center for Environmental Health, D-85764 Neuherberg, Germany.
142
Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala 75185, Sweden.
143
Montreal Heart Institute, Montreal, Quebec H1T 1C8, Canada.
144
Institute for Community Medicine, University Medicine Greifswald, D-17475 Greifswald, Germany.
145
The Genetics of Obesity and Related Metabolic Traits Program, The Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
146
School of Social and Community Medicine, University of Bristol, Bristol BS8 2BN, UK.
147
Institute of Molecular and Cell Biology, University of Tartu, Tartu 51010, Estonia.
148
Farr Institute of Health Informatics Research, University College London, London NW1 2DA, UK.
149
The Center for Observational Research, Amgen, Inc., Thousand Oaks, California 91320, USA.
150
Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche, Cagliari, Sardinia 09042, Italy.
151
Center for Evidence-based Healthcare, University Hospital Carl Gustav Carus, Technische Universität Dresden, D-01307 Dresden, Germany.
152
Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians-Universität, D-81377 Munich, Germany.
153
Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-Universität, D-81377 Munich, Germany.
154
Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia 6009, Australia.
155
Laboratory of Genetics, National Institute on Aging, Baltimore, Maryland 21224, USA.
156
Department of Genomics, Life & Brain Center, University of Bonn, 53127 Bonn, Germany.
157
Institute of Human Genetics, University of Bonn, 53127 Bonn, Germany.
158
Department of Epidemiology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
159
Department of Epidemiology and Biostatistics, Institute for Research in Extramural Medicine, Institute for Health and Care Research, VU University Medical Center, 1081BT Amsterdam, The Netherlands.
160
Department of Internal Medicine, Division of Endocrinology and Metabolism, Medical University of Graz, 8036 Graz, Austria.
161
Institute of Physiology, University Medicine Greifswald, D-17495 Karlsburg, Germany.
162
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
163
Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02215, USA.
164
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz 8036, Austria.
165
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.
166
National Cancer Institute, Bethesda, Maryland 20892, USA.
167
Icelandic Heart Association, Kopavogur 201, Iceland.
168
University of Iceland, Reykjavik 101, Iceland.
169
Molecular & Cellular Therapeutics, Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland.
170
deCODE Genetics, Amgen Inc., Reykjavik 101, Iceland.
171
Department of Medical Sciences, Molecular Medicine, Uppsala University, Uppsala 75144, Sweden.
172
National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK.
173
Department of Public Health Sciences, Stritch School of Medicine, Loyola University of Chicago, Maywood, Illinois 61053, USA.
174
Institute of Epidemiology II, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany, D-85764 Neuherberg, Germany.
175
Department of Oncology, University of Cambridge, Cambridge CB2 0QQ, UK.
176
Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg 413 45, Sweden.
177
Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC University Medical Centre, 3000 CB Rotterdam, The Netherlands.
178
Department for Health Evidence, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands.
179
Department of Genetics, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands.
180
Department of Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.
181
Genetics, GlaxoSmithKline, King of Prussia, Pennsylvania 19406, USA.
182
German Center for Cardiovascular Research, partner site Hamburg/Lubeck/Kiel, 23562 Lubeck, Germany.
183
Institut für Integrative und Experimentelle Genomik, Universität zu Lübeck, D-23562 Lübeck, Germany.
184
Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, 9037 Tromsø, Norway.
185
MRC Unit for Lifelong Health and Ageing at University College London, London WC1B 5JU, UK.
186
Diabetes Complications Research Centre, Conway Institute, School of Medicine and Medical Sciences, University College Dublin, Dublin 4, Ireland.
187
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
188
Lady Davis Institute, Departments of Human Genetics, Epidemiology and Biostatistics, McGill University, Montréal, Québec H3T1E2, Canada.
189
Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm 17176, Sweden.
190
Department of Medicine, Columbia University College of Physicians and Surgeons, New York 10032, USA.
191
Biosciences Research Division, Department of Primary Industries, Victoria 3083, Australia.
192
Department of Food and Agricultural Systems, University of Melbourne, Victoria 3010, Australia.
193
Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
194
State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China.
195
NIHR Oxford Biomedical Research Centre, OUH Trust, Oxford OX3 7LE, UK.
196
Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
197
Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.
198
Center for Genome Science, National Institute of Health, Chungcheongbuk-do, Chungbuk 363-951, Republic of Korea.
199
Harvard School of Public Health, Department of Biostatistics, Harvard University, Boston, Massachusetts 2115, USA.
200
Department of Genetics, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, New Haven, Connecticut 06520, USA.
201
College of Information Science and Technology, Dalian Maritime University, Dalian, Liaoning 116026, China.
202
Nephrology Research, Centre for Public Health, Queen's University of Belfast, Belfast, County Down BT9 7AB, UK.
203
Section of General Internal Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
204
Department of Statistics, University of Oxford, 1 South Parks Road, Oxford OX1 3TG, UK.
205
MRC Harwell, Harwell Science and Innovation Campus, Harwell OX11 0QG, UK.
206
Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland 4059, Australia.
207
Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.
208
Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 113-8510 Tokyo, Japan.
209
Genome Institute of Singapore, Agency for Science, Technology and Research, 138672 Singapore.
210
Department of Biomedical Engineering and Computational Science, Aalto University School of Science, Helsinki FI-00076, Finland.
211
Department of Medicine, Division of Nephrology, Helsinki University Central Hospital, FI-00290 Helsinki, Finland.
212
Folkhälsan Institute of Genetics, Folkhälsan Research Center, FI-00290 Helsinki, Finland.
213
Laboratory for Cardiovascular Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.
214
Division of Disease Diversity, Bioresource Research Center, Tokyo Medical and Dental University, 113-8510 Tokyo, Japan.
215
Division of Epidemiology, Department of Medicine; Vanderbilt Epidemiology Center; and Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee 37075, USA.
216
Nuffield Department of Obstetrics & Gynaecology, University of Oxford, Oxford OX3 7BN, UK.
217
Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri 63110, USA.
218
Department of Epidemiology and Public Health, EA3430, University of Strasbourg, Faculty of Medicine, Strasbourg, France.
219
Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9700RB Groningen, The Netherlands.
220
Pathology and Laboratory Medicine, The University of Western Australia, Perth, Western Australia 6009, Australia.
221
Cedars-Sinai Diabetes and Obesity Research Institute, Los Angeles, California 90048, USA.
222
Institute of Social and Preventive Medicine (IUMSP), Centre Hospitalier Universitaire Vaudois and University of Lausanne, 1010 Lausanne, Switzerland.
223
Ministry of Health, Victoria, Republic of Seychelles.
224
University of Milano, Bicocca, 20126, Italy.
225
Harvard Medical School, Boston, Massachusetts 02115, USA.
226
Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, Tennessee 37203, USA.
227
Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee 37232, USA.
228
Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts 02118, USA.
229
Department of Health Sciences, University of Milano, I 20142, Italy.
230
Fondazione Filarete, Milano I 20139, Italy.
231
Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
232
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
233
Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK.
234
Clinic of Cardiology, West-German Heart Centre, University Hospital Essen, 45147 Essen, Germany.
235
Department of General Practice and Primary Health Care, University of Helsinki, FI-00290 Helsinki, Finland.
236
Unit of General Practice, Helsinki University Central Hospital, Helsinki 00290, Finland.
237
Department of Internal Medicine B, University Medicine Greifswald, D-17475 Greifswald, Germany.
238
DZHK (Deutsches Zentrum für Herz-Kreislaufforschung - German Centre for Cardiovascular Research), partner site Greifswald, D-17475 Greifswald, Germany.
239
Department of Internal Medicine, University of Pisa, 56100 Pisa, Italy.
240
National Research Council Institute of Clinical Physiology, University of Pisa, 56124 Pisa, Italy.
241
Department of Cardiology, Toulouse University School of Medicine, Rangueil Hospital, 31400 Toulouse, France.
242
Robertson Center for Biostatistics, University of Glasgow, Glasgow G12 8QQ, UK.
243
UWI Solutions for Developing Countries, The University of the West Indies, Mona, Kingston 7, Jamaica.
244
NorthShore University HealthSystem, Evanston, IL 60201, University of Chicago, Chicago, Illinois, USA.
245
Leeds MRC Medical Bioinformatics Centre, University of Leeds, Leeds LS2 9LU, UK.
246
Institute of Biomedical & Clinical Science, University of Exeter, Barrack Road, Exeter EX2 5DW, UK.
247
Center for Biomedicine, European Academy Bozen, Bolzano (EURAC), Bolzano 39100, Italy (affiliated institute of the University of Lübeck, D-23562 Lübeck, Germany).
248
Division of Genomic Medicine, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
249
Institute of Cardiovascular Science, University College London, London WC1E 6BT, UK.
250
Department of Vascular Medicine, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands.
251
Centre for Cardiovascular Genetics, Institute Cardiovascular Sciences, University College London, London WC1E 6JJ, UK.
252
Cardiovascular Genetics Division, Department of Internal Medicine, University of Utah, Salt Lake City, Utah 84108, USA.
253
Sansom Institute for Health Research, University of South Australia, Adelaide 5000, South Australia, Australia.
254
School of Population Health, University of South Australia, Adelaide 5000, South Australia, Australia.
255
South Australian Health and Medical Research Institute, Adelaide, South Australia 5000, Australia.
256
Population, Policy, and Practice, University College London Institute of Child Health, London WC1N 1EH, UK.
257
Hannover Unified Biobank, Hannover Medical School, Hannover, D-30625 Hannover, Germany.
258
National Institute for Health and Welfare, FI-90101 Oulu, Finland.
259
MRC Health Protection Agency (HPA) Centre for Environment and Health, School of Public Health, Imperial College London, London W2 1PG, UK.
260
Unit of Primary Care, Oulu University Hospital, FI-90220 Oulu, Finland.
261
Institute of Health Sciences, University of Oulu, FI-90014 Oulu, Finland.
262
Durrer Center for Cardiogenetic Research, Interuniversity Cardiology Institute Netherlands (ICIN), 3501 DG Utrecht, The Netherlands.
263
Interuniversity Cardiology Institute of the Netherlands (ICIN), 3501 DG Utrecht, The Netherlands.
264
Unit of Primary Health Care/General Practice, Oulu University Hospital, FI-90220 Oulu, Finland.
265
Department of Urology, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands.
266
Imperial College Healthcare NHS Trust, London W12 0HS, UK.
267
Department of Epidemiology and Public Health, University College London, London WC1E 6BT, UK.
268
Department of Biological and Social Epidemiology, University of Essex, Wivenhoe Park, Colchester, Essex CO4 3SQ, UK.
269
Department of Medicine, Kuopio University Hospital and University of Eastern Finland, FI-70210 Kuopio, Finland.
270
Department of Physiology, Institute of Biomedicine, University of Eastern Finland, Kuopio Campus, FI-70211 Kuopio, Finland.
271
Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital and University of Eastern Finland, FI-70210 Kuopio, Finland.
272
Department of Clinical Chemistry, Fimlab Laboratories and School of Medicine University of Tampere, FI-33520 Tampere, Finland.
273
Steno Diabetes Center A/S, Gentofte DK-2820, Denmark.
274
Lund University Diabetes Centre and Department of Clinical Science, Diabetes & Endocrinology Unit, Lund University, Malmö 221 00, Sweden.
275
Institut Universitaire de Cardiologie et de Pneumologie de Québec, Faculty of Medicine, Laval University, Quebec, QC G1V 0A6, Canada.
276
Institute of Nutrition and Functional Foods, Laval University, Quebec, QC G1V 0A6, Canada.
277
Department of Biostatistics, University of Washington, Seattle, Washington 98195, USA.
278
Department of Surgery, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
279
Department of Biostatistics, University of Liverpool, Liverpool L69 3GA, UK.
280
Department of Pediatrics, University of Iowa, Iowa City, Iowa 52242, USA.
281
Illumina, Inc, Little Chesterford, Cambridge CB10 1XL, UK.
282
University of Groningen, University Medical Center Groningen, Department of Pulmonary Medicine and Tuberculosis, Groningen, The Netherlands.
283
Department of Neurology, General Central Hospital, Bolzano 39100, Italy.
284
Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, FI-20521 Turku, Finland.
285
Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, FI-20521 Turku, Finland.
286
Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana 70808, USA.
287
Université de Montréal, Montreal, Quebec H1T 1C8, Canada.
288
Center for Systems Genomics, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
289
Croatian Centre for Global Health, Faculty of Medicine, University of Split, 21000 Split, Croatia.
290
South Carelia Central Hospital, 53130 Lappeenranta, Finland.
291
Paul Langerhans Institute Dresden, German Center for Diabetes Research (DZD), 01307 Dresden, Germany.
292
International Centre for Circulatory Health, Imperial College London, London W2 1PG, UK.
293
Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
294
Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
295
Geriatric Research and Education Clinical Center, Vetrans Administration Medical Center, Baltimore, Maryland 21201, USA.
296
Helsinki University Central Hospital Heart and Lung Center, Department of Medicine, Helsinki University Central Hospital, FI-00290 Helsinki, Finland.
297
Sorbonne Universités, UPMC Univ Paris 06, UMR S 1166, F-75013 Paris, France.
298
INSERM, UMR S 1166, Team Genomics and Physiopathology of Cardiovascular Diseases, F-75013 Paris, France.
299
Institute for Cardiometabolism And Nutrition (ICAN), F-75013 Paris, France.
300
Department of Kinesiology, Laval University, Quebec QC G1V 0A6, Canada.
301
Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano & Centro Cardiologico Monzino, Instituto di Ricovero e Cura a Carattere Scientifico, Milan 20133, Italy.
302
Department of Food Science and Nutrition, Laval University, Quebec QC G1V 0A6, Canada.
303
Department of Internal Medicine, University Hospital (CHUV) and University of Lausanne, Lausanne 1011, Switzerland.
304
Department of Nutrition, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
305
Institut Pasteur de Lille; INSERM, U744; Université de Lille 2; F-59000 Lille, France.
306
Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
307
Department of Medicine, Stanford University School of Medicine, Palo Alto, California 94304, USA.
308
Lee Kong Chian School of Medicine, Imperial College London and Nanyang Technological University, Singapore, 637553 Singapore, Singapore.
309
Health Science Center at Houston, University of Texas, Houston, Texas 77030, USA.
310
Department of Medicine, Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
311
Department of Epidemiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
312
School of Population Health, The University of Western Australia, Nedlands, Western Australia 6009, Australia.
313
Albert Einstein College of Medicine, Department of Epidemiology and Population Health, Belfer 1306, New York 10461, USA.
314
Center for Human Genetics, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157, USA.
315
Synlab Academy, Synlab Services GmbH, 68163 Mannheim, Germany.
316
Department of Clinical Medicine, Copenhagen University, 2200 Copenhagen, Denmark.
317
Department of Clinical Genetics, Erasmus MC University Medical Center, 3000 CA Rotterdam, The Netherlands.
318
Finnish Diabetes Association, Kirjoniementie 15, FI-33680 Tampere, Finland.
319
Pirkanmaa Hospital District, FI-33521 Tampere, Finland.
320
Center for Non-Communicable Diseases, Karatchi, Pakistan.
321
Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
322
BHF Glasgow Cardiovascular Research Centre, Division of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow G12 8TA, UK.
323
Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10580, USA.
324
Faculty of Medicine, University of Iceland, Reykjavik 101, Iceland.
325
Institute for Health Research, University Hospital of La Paz (IdiPaz), 28046 Madrid, Spain.
326
Diabetes Research Group, King Abdulaziz University, 21589 Jeddah, Saudi Arabia.
327
Centre for Vascular Prevention, Danube-University Krems, 3500 Krems, Austria.
328
Department of Public Health and Clinical Nutrition, University of Eastern Finland, Finland.
329
Research Unit, Kuopio University Hospital, FI-70210 Kuopio, Finland.
330
Institute of Cellular Medicine, Newcastle University, Newcastle NE1 7RU, UK.
331
Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, D-17475 Greifswald, Germany.
332
Institute of Medical Informatics, Biometry and Epidemiology, Chair of Epidemiology, Ludwig-Maximilians-Universität, D-85764 Munich, Germany.
333
Klinikum Grosshadern, D-81377 Munich, Germany.
334
Institute of Epidemiology I, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany, D-85764 Neuherberg, Germany.
335
Department of Pulmonology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
336
Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, 21589 Jeddah, Saudi Arabia.
337
Division of Population Health Sciences & Education, St George's, University of London, London SW17 0RE, UK.
338
Oxford NIHR Biomedical Research Centre, Oxford University Hospitals NHS Trust, Oxford OX3 7LJ, UK.
339
Clinical Epidemiology, Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), Jena University Hospital, 07743 Jena, Germany.
340
Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA.
341
Service of Medical Genetics, CHUV University Hospital, 1011 Lausanne, Switzerland.
342
University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 OQQ, UK.
343
NIHR Cambridge Biomedical Research Centre, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 OQQ, UK.
344
Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
345
The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
#
Contributed equally

Abstract

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

Comment in

PMID:
25673413
PMCID:
PMC4382211
DOI:
10.1038/nature14177
[Indexed for MEDLINE]
Free PMC Article

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