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Nat Commun. 2016 Nov 23;7:13357. doi: 10.1038/ncomms13357.

A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape.

Ried JS1, Jeff M J2, Chu AY3, Bragg-Gresham JL4, van Dongen J5, Huffman JE6, Ahluwalia TS7,8,9, Cadby G10, Eklund N11, Eriksson J12, Esko T13,14,15,16, Feitosa MF17, Goel A18,19, Gorski M20,21, Hayward C6, Heard-Costa NL22,23, Jackson AU24, Jokinen E25, Kanoni S26,27, Kristiansson K11,28, Kutalik Z29,30,31, Lahti J32,33, Luan J34, Mägi R15,19, Mahajan A19, Mangino M35, Medina-Gomez C36,37, Monda KL38,39, Nolte IM40, Pérusse L41,42, Prokopenko I19,43,44, Qi L45,46, Rose LM3, Salvi E47,48, Smith MT49, Snieder H40, Stančáková A50, Ju Sung Y51, Tachmazidou I26, Teumer A52,53, Thorleifsson G54, van der Harst P55,56,57, Walker RW2,58, Wang SR16,59,60,61, Wild SH62, Willems SM63, Wong A64, Zhang W65,66, Albrecht E1, Couto Alves A67, Bakker SJ68, Barlassina C47,48, Bartz TM49,69,70, Beilby J71,72, Bellis C73,74, Bergman RN75, Bergmann S29,30, Blangero J76, Blüher M77,78, Boerwinkle E79, Bonnycastle LL80, Bornstein SR81, Bruinenberg M82, Campbell H62, Chen YI83, Chiang CW84, Chines PS80, Collins FS80, Cucca F85, Cupples LA22, D'Avila F47,48, de Geus EJ5,86, Dedoussis G87, Dimitriou M26,87, Döring A88,89, Eriksson JG32,90,91, Farmaki AE87, Farrall M18,19, Ferreira T19, Fischer K15, Forouhi NG34, Friedrich N92, Gjesing AP7, Glorioso N93, Graff M38, Grallert H89,94,95, Grarup N7, Gräßler J96, Grewal J65,66, Hamsten A97,98,99, Harder MN7, Hartman CA100, Hassinen M101, Hastie N6, Hattersley AT102, Havulinna AS11, Heliövaara M11, Hillege H57, Hofman A36, Holmen O103, Homuth G53, Hottenga JJ5, Hui J71,72,104, Husemoen LL105, Hysi PG35, Isaacs A63, Ittermann T52, Jalilzadeh S18,19, James AL106, Jørgensen T107,108,109, Jousilahti P11, Jula A11, Marie Justesen J7, Justice AE38, Kähönen M110,111, Karaleftheri M112, Tee Khaw K113, Keinanen-Kiukaanniemi SM114,115, Kinnunen L116, Knekt PB11, Koistinen HA116,117,118, Kolcic I119, Kooner IK66, Koskinen S11, Kovacs P77, Kyriakou T18,19, Laitinen T120,121, Langenberg C34,122, Lewin AM67, Lichtner P123, Lindgren CM13,19,124, Lindström J11, Linneberg A105,107,125, Lorbeer R52, Lorentzon M12, Luben R126, Lyssenko V8,127, Männistö S11, Manunta P128, Leach IM57, McArdle WL129, Mcknight B49,70,130, Mohlke KL131, Mihailov E15, Milani L15, Mills R66, Montasser ME132, Morris AP19,133, Müller G134, Musk AW135, Narisu N80, Ong KK34,64,136, Oostra BA63, Osmond C137, Palotie A28,138, Pankow JS139, Paternoster L140, Penninx BW141, Pichler I142,143, Pilia MG144, Polašek O62,119, Pramstaller PP142,143,145,146, Raitakari OT147,148, Rankinen T149, Rao DC51,150, Rayner NW19,44,151, Ribel-Madsen R7, Rice TK51,150, Richards M44,64, Ridker PM3,152, Rivadeneira F36,37, Ryan KA132, Sanna S144, Sarzynski MA149, Scholtens S40, Scott RA34, Sebert S43,153,154, Southam L19,26, Sparsø TH7, Steinthorsdottir V54, Stirrups K26,27, Stolk RP40, Strauch K1,155, Stringham HM24, Swertz MA56, Swift AJ80, Tönjes A78, Tsafantakis E156, van der Most PJ40, Van Vliet-Ostaptchouk JV157, Vandenput L12, Vartiainen E11, Venturini C35,158, Verweij N57, Viikari JS159,160, Vitart V6, Vohl MC42,161, Vonk JM40, Waeber G162, Widén E28, Willemsen G5, Wilsgaard T163, Winkler TW21, Wright AF6, Yerges-Armstrong LM132, Hua Zhao J34, Zillikens MC37, Boomsma DI5, Bouchard C149, Chambers JC65,66,164, Chasman DI3,152, Cusi D47,48, Gansevoort RT68, Gieger C1,89,95, Hansen T7,165, Hicks AA142,143, Hu F45,46, Hveem K103, Jarvelin MR153,166,167,168, Kajantie E11,90,169,170, Kooner JS66,164,171, Kuh D64, Kuusisto J50, Laakso M50, Lakka TA101,172, Lehtimäki T173,174, Metspalu A15, Njølstad I163,175, Ohlsson C12, Oldehinkel AJ100, Palmer LJ176,177, Pedersen O7, Perola M11,15,28, Peters A89,95,178, Psaty BM70,69,179,180, Puolijoki H181, Rauramaa R101,182, Rudan I62, Salomaa V11, Schwarz PE81,183, Shudiner AR132,184, Smit JH141, Sørensen TI7,185,186, Spector TD35, Stefansson K54,187, Stumvoll M77,78, Tremblay A41, Tuomilehto J188,189,190, Uitterlinden AG36,37, Uusitupa M191,192, Völker U53,193, Vollenweider P162, Wareham NJ34, Watkins H18,19, Wilson JF6,62, Zeggini E26, Abecasis GR24, Boehnke M24, Borecki IB17, Deloukas P27,151,194, van Duijn CM63,195, Fox C22,152, Groop LC127,196, Heid IM21,197, Hunter DJ13,45,46,198, Kaplan RC199, McCarthy MI19,44,200, North KE201, O'Connell JR132, Schlessinger D202, Thorsteinsdottir U54,187, Strachan DP203, Frayling T204, Hirschhorn JN13,14,16,59,60,61,205, Müller-Nurasyid M1,155,178,206, Loos RJ2,34,58,207,208.

Author information

1
Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, 85764 Neuherberg, Germany.
2
The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
3
Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02215, USA.
4
Kidney Epidemiology and Cost Center, Internal Medicine-Nephrology, University of Michigan, Ann Arbor, Michigan 48109, USA.
5
Department of Biological Psychology, VU University, 1081BT Amsterdam, The Netherlands.
6
MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, EH4 2XU Edinburgh, Scotland.
7
Faculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, University of Copenhagen, 2100 Copenhagen, Denmark.
8
Steno Diabetes Center A/S, DK-2820 Gentofte, Denmark.
9
COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Ledreborg Allé 34, DK-2820 Copenhagen, Denmark.
10
Centre for Genetic Origins of Health and Disease, University of Western Australia, Crawley, Western Australia 6009, Australia.
11
Department of Health, National Institute for Health and Welfare (THL), FI-00271 Helsinki, Finland.
12
Department of Internal Medicine and Clinical Nutrition, Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden.
13
Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 2142, USA.
14
Divisions of Endocrinology and Genetics and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts 02115, USA.
15
Estonian Genome Center, University of Tartu, Tartu 51010, Estonia.
16
Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
17
Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, Missouri 63108, USA.
18
Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, UK.
19
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
20
Department of Nephrology, University Hospital Regensburg, 93042 Regensburg, Germany.
21
Department of Genetic Epidemiology, Institute of Epidemiology and Preventive Medicine, University of Regensburg, 93053 Regensburg, Germany.
22
National Heart, Lung, and Blood Institute, the Framingham Heart Study, Framingham, Massachusetts 01702, USA.
23
Department of Neurology, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
24
Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA.
25
Hospital for Children and Adolescents, University of Helsinki, FI-00290 Helsinki, Finland.
26
Wellcome Trust Sanger Institute, Human Genetics, Hinxton, Cambridge CB10 1SA, UK.
27
William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.
28
Institute for Molecular Medicine Finland, University of Helsinki, FI-00290 Helsinki, Finland.
29
Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland.
30
Department of Medical Genetics, University of Lausanne, Lausanne, 1005, Switzerland.
31
Institute of Social and Preventive Medicine, University Hospital Lausanne (CHUV), 1010 Lausanne, Switzerland.
32
Folkhälsan Research Centre, FI-00290 Helsinki, Finland.
33
Institute of Behavioural Sciences, University of Helsinki, FI-00014 Helsinki, Finland.
34
MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
35
Department of Twin Research and Genetic Epidemiology, King's College London, London SE1 7EH, UK.
36
Department of Epidemiology, Erasmus Medical Center, 3015GE Rotterdam, The Netherlands.
37
Department of Internal Medicine, Erasmus Medical Center, 3015GE Rotterdam, The Netherlands.
38
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
39
The Center for Observational Research, Amgen Inc., Thousand Oaks, California 91320-1799, USA.
40
Department of Epidemiology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands.
41
Department of Kinesiology, Laval University, Québec, Québec, Canada G1V 0A6.
42
Institute of Nutrition and Functional Foods, Laval University, Québec, Québec, Canada G1V 0A6.
43
Department of Genomics of Common Disease, School of Public Health, Imperial College London, London W12 0NN, UK.
44
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UK.
45
Department of Medicine, Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
46
Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
47
Department of Health Sciences, University of Milano at San Paolo Hospital, 20139 Milano, Italy.
48
Filarete Foundation, Genomic and Bioinformatics Unit, Milano 20139, Italy.
49
Department of Biostatistics, University of Washington, Seattle, Washington 98195, USA.
50
Department of Medicine, University of Eastern Finland and Kuopio University Hospital, 70210 Kuopio, Finland.
51
Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
52
Institute for Community Medicine, University Medicine Greifswald, 17475 Greifswald, Germany.
53
Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, 17475 Greifswald, Germany.
54
deCODE Genetics, Amgen inc., 101 Reykjavik, Iceland.
55
Durrer Center for Cardiogenetic Research, Interuniversity Cardiology Institute Netherlands-Netherlands Heart Institute, 3501 DG Utrecht, The Netherlands.
56
Department of Genetics, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands.
57
Department of Cardiology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, Netherlands.
58
The Department of Preventive Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
59
Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
60
Division of Endocrinology, Boston Children's Hospital, Boston, Massachusetts 02115, USA.
61
Divisions of Genetics and Endocrinology and Program in Genomics, Boston's Children's Hospital, Boston, Massachusetts 02115, USA.
62
Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, EH8 9AG Teviot Place, Edinburgh, Scotland.
63
Department of Epidemiology, Genetic Epidemiology Unit, Erasmus University Medical Center, 3015GE Rotterdam, The Netherlands.
64
MRC Unit for Lifelong Health &Ageing at UCL, London WC1B 5JU, UK.
65
Department of Epidemiology and Biostatistics, Imperial College London, London W2 1PG, UK.
66
Ealing Hospital NHS Trust, Middlesex UB1 3HW, UK.
67
Department of Epidemiology and Biostatistics, MRC Health Protection Agency (HPA) Centre for Environment and Health, School of Public Health, Imperial College, London W12 0NN, UK.
68
Department of Medicine, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, Netherlands.
69
Department of Medicine, University of Washington, Seattle, Washington 98101, USA.
70
Cardiovascular Health Research Unit, University of Washington, Seattle, Washington 98101, USA.
71
Pathwest Laboratory Medicine of Western Australia, Nedlands, Western Australia 6009, Australia.
72
School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands, Western Australia 6009, Australia.
73
Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland 4001, Australia.
74
Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research of Singapore, Singapore 138672, Singapore.
75
Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
76
South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley, Brownsville, Texas 78520, USA.
77
University of Leipzig, IFB Adiposity Diseases, 04103 Leipzig, Germany.
78
Department of Medicine, University of Leipzig, 04103 Leipzig, Germany.
79
Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Science Center, Houston, Texas 77030, USA.
80
Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland 20892, USA.
81
Medical Faculty Carl Gustav Carus, Department of Medicine III, University of Dresden, 01307 Dresden, Germany.
82
University of Groningen, University Medical Center Groningen, The LifeLines Cohort Study, 9700 RB Groningen, The Netherlands.
83
Los Angeles BioMedical Resesarch Institute at Harbor-UCLA Medical Center, Torrance, California 90502, USA.
84
Department of Psychiatry, University of California, Los Angeles, California 90095, USA.
85
University of Sassari, 07100 Sassari, Italy.
86
EMGO Institute for Health and Care Research, VU University Medical Center, 1081 BT Amsterdam, The Netherlands.
87
Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, 17671 Athens, Greece.
88
Institute of Epidemiology I, Helmholtz Zentrum München-German Research Center for Environmental Health, 85764 Neuherberg, Germany.
89
Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, 85764 Neuherberg, Germany.
90
Department of Chronic Disease Prevention, National Institute for Health and Welfare, FI-00271 Helsinki, Finland.
91
Department of General Practice and Primary Health Care, University of Helsinki, FI-00014 Helsinki, Finland.
92
Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, 17475 Greifswald, Germany.
93
Hypertension and Related Disease Centre, AOU-University of Sassari, 7100 Sassari, Italy.
94
German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany.
95
Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, 85764 Neuherberg, Germany.
96
Department of Medicine III, Pathobiochemistry, Technische Universitaet, 01307 Dresden, Germany.
97
Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
98
Department of Medicine Solna, Atherosclerosis Research Unit, Karolinska Institutet, 17176 Stockholm 17176, Sweden.
99
Center for Molecular Medicine, Karolinska University Hospital, 17176 Stockholm, Sweden.
100
University of Groningen, University Medical Center Groningen, Interdisciplinary Center Psychopathology and Emotion Regulation, 9700 RB Groningen, The Netherlands.
101
Kuopio Research Institute of Exercise Medicine, 70100 Kuopio, Finland.
102
Institue of Biomedical &Clinical Science, University of Exeter, Barrack Road, Exeter EX2 5DW, UK.
103
Department of Public Health and General Practice, Norwegian University of Science and Technology, 7489 Trondheim, Norway.
104
School of Population Health, University of Western Australia, Nedlands, Western Australia 6009, Australia.
105
Research Centre for Prevention and Health, Glostrup Hospital, 2600 Glostrup, Denmark.
106
Department of Pulmonary Physiology and Sleep Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia 6009, Australia.
107
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
108
Faculty of Medicine, University of Aalborg, 9220 Aalborg, Denmark.
109
Research Centre for Prevention and Health, Capital Region of Denmark, DK2600 Glostrup, Denmark.
110
Department of Clinical Physiology, Tampere University Hospital, FI-33521 Tampere, Finland.
111
Department of Clinical Physiology, University of Tampere School of Medicine, FI-33014 Tampere, Finland.
112
Echinos Medical Centre, 67300 Echinos, Greece.
113
Clinical Gerontology Unit, Box 251, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK.
114
Faculty of Medicine, Institute of Health Sciences, University of Oulu, Oulu F1-90014, Finland.
115
Unit of General Practice, Oulu University Hospital, Oulu FI-90029, Finland.
116
National Institute for Health and Welfare, FI-00271 Helsinki, Finland.
117
Department of Medicine and Abdominal Center: Endocrinology, University of Helsinki and Helsinki University Central Hospital,, 00029 Helsinki, Finland.
118
Minerva Foundation Institute for Medical Research, 00290 Helsinki, Finland.
119
Department of Public Health, Faculty of Medicine, University of Split, 21000 Split, Croatia.
120
Kuopio University Hospital, 70029 Kuopio, Finland.
121
Department of Clinical Physiology and Nuclear Medicine, University of Eastern Finland, FI-70211 Kuopio, Finland.
122
Department of Epidemiology and Public Health, UCL, London WC1E 6BT, UK.
123
Institute of Human Genetics, Helmholtz Zentrum München-German Research Center for Environmental Health, 85764 Neuherberg, Germany.
124
The Big Data Institute, University of Oxford, Oxford OX3 7LJ, UK.
125
Department of Clinical Experimental Research, Rigshospitalet, 2600 Glostrup, Denmark.
126
Strangeways Research Laboratory Wort's Causeway, Cambridge CB1 8RN, UK.
127
Lund University Diabetes Centre and Department of Clinical Science, Diabetes &Endocrinology Unit, Lund University, 221 00 Malmö, Sweden.
128
Chair of Nephrology, Università Vita Salute San Raffaele and Genomics of Renal Diseases and Hypertension Unit, IRCCS San Raffaele Scientific Institute, Milan 20139, Italy.
129
School of Social and Community Medicine, University of Bristol, Bristol BS82BN, UK.
130
Divison of Public Health Sciences, Program in Biostatistics and Biomathematics, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
131
Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
132
Division of Endocrinology, Diabetes &Nutrition, Department of Medicine, Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
133
Department of Biostatistics, University of Liverpool, Liverpool L69 3GA, UK.
134
Center for Evidence Based Healthcare, University of Dresden, Medical Faculty Carl Gustav Carus, Dresden, 01307, Germany.
135
Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, West Australia 6009, Australia.
136
Department of Paediatrics, University of Cambridge, Cambridge CB2 0QQ, UK.
137
MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
138
Massachusetts General Hospital, Center for Human Genetic Research, Psychiatric and Neurodevelopmental Genetics Unit, Boston, Massachusetts 02114, USA.
139
Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota 55455-0381, USA.
140
MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol BS8 1TH, UK.
141
Department of Psychiatry and EMGO Institute for Health and Care Research, VU University Medical Center, AJ Ernstraat 1887, 1081 HL Amsterdam, The Netherlands.
142
Center for Biomedicine, European Academy Bozen/Bolzano (EURAC), 39100 Bolzano, Italy.
143
Affiliated Institute of the University of Lübeck, 23562 Lübeck, Germany.
144
Istituto di Ricerca Genetica e Biomedica, CNR, 9042 Monserrato, Italy.
145
Department of Neurology, University of Lübeck, 23562 Lübeck, Germany.
146
Department of Neurology, General Central Hospital, 39100 Bolzano, Italy.
147
Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, FI-20521 Turku, Finland.
148
Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, FI-20520 Turku, Finland.
149
Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana 70808, USA.
150
Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
151
Wellcome Trust Sanger Institute, Human Genetics, Hinxton CB10 1HH, UK.
152
Harvard Medical School, Boston, Massachusetts, 02115, USA.
153
Biocenter Oulu, University of Oulu, Oulu FI-90014, Finland.
154
Center For Life-Course Health Research, University of Oulu, FI-90014 Oulu, Finland.
155
Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-Universität, 81377 Munich, Germany.
156
Anogia Medical Centre, 74051 Anogia, Greece.
157
Department of Endocrinology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands.
158
Institute of Ophthalmology, University College London, London EC1V 9EL, UK.
159
Department of Medicine, University of Turku, FI-20521 Turku, Finland.
160
Division of Medicine, Turku University Hospital, Turku, Finland.
161
School of Nutrition, Laval University, Québec, Québec, Canada G1V 0A6.
162
Department of Internal Medicine, University Hospital Lausanne (CHUV) and University of Lausanne, 1011 Lausanne, Switzerland.
163
Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, 9037 Tromsø, Norway.
164
Imperial College Healthcare NHS Trust, London W12 0HS, UK.
165
Faculty of Health Sciences, University of Southern Denmark, 5000 Odense, Denmark.
166
Unit of Primary Care, Oulu University Hospital, 90029 OYS Oulu, Finland.
167
Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment &Health, School of Public Health, Imperial College London W12 0NN, UK.
168
Faculty of Medicine, Center for Life Course Epidemiology, University of Oulu, P.O.Box 5000, FI-90014 Oulu, Finland.
169
Children's Hospital, Helsinki University Hospital and University of Helsinki, FI-00029 Helsinki, Finland.
170
Department of Obstetrics and Gynecology, MRC Oulu, Oulu University Hospital and University of Oulu, FI-90029 Oulu, Finland.
171
National Heart and Lung Institute, Imperial College London, London W12 0NN, UK.
172
Department of Physiology, Institute of Biomedicine, University of Eastern Finland, Kuopio Campus, 70210 Kuopio, Finland.
173
Department of Clinical Chemistry, University of Tampere School of Medicine, FI-33014 Tampere, Finland.
174
Department of Clinical Chemistry, Fimlab Laboratories and School of Medicine, University of Tampere, FI-33520 Tampere, Finland.
175
Department of Clinical Medicine, Faculty of Health Sciences, University of Tromsø, 9037 Tromsø, Norway.
176
School of Public Health, University of Adelaide, Adelaide, South Australia 5005, Australia.
177
Robinson Research Institute, University of Adelaide, Adelaide, South Australia 5005, Australia.
178
DZHK (German Centre for Cardiovascular Research), partnersite Munich Heart Alliance, 80802 Munich, Germany.
179
Departments of Epidemiology and Health Services, University of Washington, Seattle, Washington 98101, USA.
180
Group Health Research Institute, Group Health Cooperative, Seatte, Washington 98101, USA.
181
South Ostrobothnia Central Hospital, Seinäjoki Fi-60220, Finland.
182
Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, 70211 Kuopio, Finland.
183
Paul Langerhans Institute Dresden, German Center for Diabetes Research (DZD), Dresden 01307, Germany.
184
Geriatric Research and Education Clinical Center, Vetrans Administration Medical Center, Baltimore, Maryland 21042, USA.
185
MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol BS82BN, UK.
186
Institute of Preventive Medicine, Bispebjerg and Frederiksberg Hospital, The Capital Region, 2000 Frederiksberg, Denmark.
187
Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland.
188
Diabetes Prevention Unit, National Institute for Health and Welfare, FI-00271 Helsinki, Finland.
189
Centre for Vascular Prevention, Danube-University Krems, 3500 Krems, Austria.
190
Diabetes Research Group, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
191
Department of Public Health and Clinical Nutrition, University of Eastern Finland, 70211 Kuopio, Finland.
192
Research Unit, Kuopio University Hospital, 70029 Kuopio, Finland.
193
DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, 17475 Greifswald, Germany.
194
Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah 21589, Saudi Arabia.
195
Center for Medical Systems Biology, 2300 Leiden, The Netherlands.
196
Finnish Institute for Molecular Medicine (FIMM), Helsinki University, 00014 Helsinki, Finland.
197
Institute of Genetic Epidemiology, Helmholtz Zentrum München, Neuherberg 85764, Germany.
198
Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
199
Department of Epidemiology and Popualtion Health, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
200
Oxford NIHR Biomedical Research Centre, Oxford OX3 7LJ, UK.
201
Department of Epidemiology, Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7400, USA.
202
National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA.
203
Population Health Research Institute, St George's, University of London, London SW17 0RE, UK.
204
Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter EX1 2LU, UK.
205
Metabolism Initiative, Broad Institute, Cambridge, Massachusetts 02142, USA.
206
Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians-Universität, 81377 Munich, Germany.
207
The Genetics of Obesity and Related Metabolic Traits Program, The Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
208
The Mindich Child Health and Development Institute, The Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.

Abstract

Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.

PMID:
27876822
PMCID:
PMC5114527
DOI:
10.1038/ncomms13357
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Kari Stefansson, Valgerdur Steinthorsdottir, Gudmar Thorleifsson and Unnur Thorsteinsdottir are used by deCODE Genetics/Amgen inc. Gérard Waeber and Peter Vollenweider received an unrestricted grant from GSK to build the CoLaus study. Bruce M. Psaty serves on a DSMB for a clinical trial of a device funded by the manufacturer (Zoll LifeCor).

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