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

Janina S Ried¹, Janina Jeff M², Audrey Y Chu³, Jennifer L Bragg-Gresham⁴, Jenny van Dongen⁵, Jennifer E Huffman⁶, Tarunveer S Ahluwalia^{7

8

9}, Gemma Cadby¹⁰, Niina Eklund¹¹, Joel Eriksson¹², Tõnu Esko^{13

14

15

16}, Mary F Feitosa¹⁷, Anuj Goel^{18

19}, Mathias Gorski^{20

21}, Caroline Hayward⁶, Nancy L Heard-Costa^{22

23}, Anne U Jackson²⁴, Eero Jokinen²⁵, Stavroula Kanoni^{26

27}, Kati Kristiansson^{11

28}, Zoltán Kutalik^{29

30

31}, Jari Lahti^{32

33}, Jian'an Luan³⁴, Reedik Mägi^{15

19}, Anubha Mahajan¹⁹, Massimo Mangino³⁵, Carolina Medina-Gomez^{36

37}, Keri L Monda^{38

39}, Ilja M Nolte⁴⁰, Louis Pérusse^{41

42}, Inga Prokopenko^{19

43

44}, Lu Qi^{45

46}, Lynda M Rose³, Erika Salvi^{47

48}, Megan T Smith⁴⁹, Harold Snieder⁴⁰, Alena Stančáková⁵⁰, Yun Ju Sung⁵¹, Ioanna Tachmazidou²⁶, Alexander Teumer^{52

53}, Gudmar Thorleifsson⁵⁴, Pim van der Harst^{55

56

57}, Ryan W Walker^{2

58}, Sophie R Wang^{16

59

60

61}, Sarah H Wild⁶², Sara M Willems⁶³, Andrew Wong⁶⁴, Weihua Zhang^{65

66}, Eva Albrecht¹, Alexessander Couto Alves⁶⁷, Stephan J L Bakker⁶⁸, Cristina Barlassina^{47

48}, Traci M Bartz^{49

69

70}, John Beilby^{71

72}, Claire Bellis^{73

74}, Richard N Bergman⁷⁵, Sven Bergmann^{29

30}, John Blangero⁷⁶, Matthias Blüher^{77

78}, Eric Boerwinkle⁷⁹, Lori L Bonnycastle⁸⁰, Stefan R Bornstein⁸¹, Marcel Bruinenberg⁸², Harry Campbell⁶², Yii-Der Ida Chen⁸³, Charleston W K Chiang⁸⁴, Peter S Chines⁸⁰, Francis S Collins⁸⁰, Fracensco Cucca⁸⁵, L Adrienne Cupples²², Francesca D'Avila^{47

48}, Eco J C de Geus^{5

86}, George Dedoussis⁸⁷, Maria Dimitriou^{26

87}, Angela Döring^{88

89}, Johan G Eriksson^{32

90

91}, Aliki-Eleni Farmaki⁸⁷, Martin Farrall^{18

19}, Teresa Ferreira¹⁹, Krista Fischer¹⁵, Nita G Forouhi³⁴, Nele Friedrich⁹², Anette Prior Gjesing⁷, Nicola Glorioso⁹³, Mariaelisa Graff³⁸, Harald Grallert^{89

94

95}, Niels Grarup⁷, Jürgen Gräßler⁹⁶, Jagvir Grewal^{65

66}, Anders Hamsten^{97

98

99}, Marie Neergaard Harder⁷, Catharina A Hartman¹⁰⁰, Maija Hassinen¹⁰¹, Nicholas Hastie⁶, Andrew Tym Hattersley¹⁰², Aki S Havulinna¹¹, Markku Heliövaara¹¹, Hans Hillege⁵⁷, Albert Hofman³⁶, Oddgeir Holmen¹⁰³, Georg Homuth⁵³, Jouke-Jan Hottenga⁵, Jennie Hui^{71

72

104}, Lise Lotte Husemoen¹⁰⁵, Pirro G Hysi³⁵, Aaron Isaacs⁶³, Till Ittermann⁵², Shapour Jalilzadeh^{18

19}, Alan L James¹⁰⁶, Torben Jørgensen^{107

108

109}, Pekka Jousilahti¹¹, Antti Jula¹¹, Johanne Marie Justesen⁷, Anne E Justice³⁸, Mika Kähönen^{110

111}, Maria Karaleftheri¹¹², Kay Tee Khaw¹¹³, Sirkka M Keinanen-Kiukaanniemi^{114

115}, Leena Kinnunen¹¹⁶, Paul B Knekt¹¹, Heikki A Koistinen^{116

117

118}, Ivana Kolcic¹¹⁹, Ishminder K Kooner⁶⁶, Seppo Koskinen¹¹, Peter Kovacs⁷⁷, Theodosios Kyriakou^{18

19}, Tomi Laitinen^{120

121}, Claudia Langenberg^{34

122}, Alexandra M Lewin⁶⁷, Peter Lichtner¹²³, Cecilia M Lindgren^{13

19

124}, Jaana Lindström¹¹, Allan Linneberg^{105

107

125}, Roberto Lorbeer⁵², Mattias Lorentzon¹², Robert Luben¹²⁶, Valeriya Lyssenko^{8

127}, Satu Männistö¹¹, Paolo Manunta¹²⁸, Irene Mateo Leach⁵⁷, Wendy L McArdle¹²⁹, Barbara Mcknight^{49

70

130}, Karen L Mohlke¹³¹, Evelin Mihailov¹⁵, Lili Milani¹⁵, Rebecca Mills⁶⁶, May E Montasser¹³², Andrew P Morris^{19

133}, Gabriele Müller¹³⁴, Arthur W Musk¹³⁵, Narisu Narisu⁸⁰, Ken K Ong^{34

64

136}, Ben A Oostra⁶³, Clive Osmond¹³⁷, Aarno Palotie^{28

138}, James S Pankow¹³⁹, Lavinia Paternoster¹⁴⁰, Brenda W Penninx¹⁴¹, Irene Pichler^{142

143}, Maria G Pilia¹⁴⁴, Ozren Polašek^{62

119}, Peter P Pramstaller^{142

143

145

146}, Olli T Raitakari^{147

148}, Tuomo Rankinen¹⁴⁹, D C Rao^{51

150}, Nigel W Rayner^{19

44

151}, Rasmus Ribel-Madsen⁷, Treva K Rice^{51

150}, Marcus Richards^{44

64}, Paul M Ridker^{3

152}, Fernando Rivadeneira^{36

37}, Kathy A Ryan¹³², Serena Sanna¹⁴⁴, Mark A Sarzynski¹⁴⁹, Salome Scholtens⁴⁰, Robert A Scott³⁴, Sylvain Sebert^{43

153

154}, Lorraine Southam^{19

26}, Thomas Hempel Sparsø⁷, Valgerdur Steinthorsdottir⁵⁴, Kathleen Stirrups^{26

27}, Ronald P Stolk⁴⁰, Konstantin Strauch^{1

155}, Heather M Stringham²⁴, Morris A Swertz⁵⁶, Amy J Swift⁸⁰, Anke Tönjes⁷⁸, Emmanouil Tsafantakis¹⁵⁶, Peter J van der Most⁴⁰, Jana V Van Vliet-Ostaptchouk¹⁵⁷, Liesbeth Vandenput¹², Erkki Vartiainen¹¹, Cristina Venturini^{35

158}, Niek Verweij⁵⁷, Jorma S Viikari^{159

160}, Veronique Vitart⁶, Marie-Claude Vohl^{42

161}, Judith M Vonk⁴⁰, Gérard Waeber¹⁶², Elisabeth Widén²⁸, Gonneke Willemsen⁵, Tom Wilsgaard¹⁶³, Thomas W Winkler²¹, Alan F Wright⁶, Laura M Yerges-Armstrong¹³², Jing Hua Zhao³⁴, M Carola Zillikens³⁷, Dorret I Boomsma⁵, Claude Bouchard¹⁴⁹, John C Chambers^{65

66

164}, Daniel I Chasman^{3

152}, Daniele Cusi^{47

48}, Ron T Gansevoort⁶⁸, Christian Gieger^{1

89

95}, Torben Hansen^{7

165}, Andrew A Hicks^{142

143}, Frank Hu^{45

46}, Kristian Hveem¹⁰³, Marjo-Riitta Jarvelin^{153

166

167

168}, Eero Kajantie^{11

90

169

170}, Jaspal S Kooner^{66

164

171}, Diana Kuh⁶⁴, Johanna Kuusisto⁵⁰, Markku Laakso⁵⁰, Timo A Lakka^{101

172}, Terho Lehtimäki^{173

174}, Andres Metspalu¹⁵, Inger Njølstad^{163

175}, Claes Ohlsson¹², Albertine J Oldehinkel¹⁰⁰, Lyle J Palmer^{176

177}, Oluf Pedersen⁷, Markus Perola^{11

15

28}, Annette Peters^{89

95

178}, Bruce M Psaty^{70

69

179

180}, Hannu Puolijoki¹⁸¹, Rainer Rauramaa^{101

182}, Igor Rudan⁶², Veikko Salomaa¹¹, Peter E H Schwarz^{81

183}, Alan R Shudiner^{132

184}, Jan H Smit¹⁴¹, Thorkild I A Sørensen^{7

185

186}, Timothy D Spector³⁵, Kari Stefansson^{54

187}, Michael Stumvoll^{77

78}, Angelo Tremblay⁴¹, Jaakko Tuomilehto^{188

189

190}, André G Uitterlinden^{36

37}, Matti Uusitupa^{191

192}, Uwe Völker^{53

193}, Peter Vollenweider¹⁶², Nicholas J Wareham³⁴, Hugh Watkins^{18

19}, James F Wilson^{6

62}, Eleftheria Zeggini²⁶, Goncalo R Abecasis²⁴, Michael Boehnke²⁴, Ingrid B Borecki¹⁷, Panos Deloukas^{27

151

194}, Cornelia M van Duijn^{63

195}, Caroline Fox^{22

152}, Leif C Groop^{127

196}, Iris M Heid^{21

197}, David J Hunter^{13

45

46

198}, Robert C Kaplan¹⁹⁹, Mark I McCarthy^{19

44

200}, Kari E North²⁰¹, Jeffrey R O'Connell¹³², David Schlessinger²⁰², Unnur Thorsteinsdottir^{54

187}, David P Strachan²⁰³, Timothy Frayling²⁰⁴, Joel N Hirschhorn^{13

14

16

59

60

61

205}, Martina Müller-Nurasyid^{1

155

178

206}, Ruth J F Loos^{2

34

58

207

208}

Affiliations

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.

PMID: 27876822
PMCID: PMC5114527
DOI: 10.1038/ncomms13357

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

Janina S Ried et al. Nat Commun. 2016.

. 2016 Nov 23:7:13357.

doi: 10.1038/ncomms13357.

Authors

Affiliations

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.

PMID: 27876822
PMCID: PMC5114527
DOI: 10.1038/ncomms13357

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.

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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).

Figures

**Figure 1. Loadings and explained variance of AvPCs for body shape.**
(a) Loadings of AvPCs, and (b) explained variance of AvPCs for body shape.

**Figure 2. Manhattan and QQ-plots of association results on AvPCs of body shape.**
P values of the first stage meta-analysis are given in the Manhattan and QQ-plots. All genome-wide significant loci are highlighted.

**Figure 3. Number of loci associated with AvPCs and known from previous GIANT analyses on BMI, WHR or height.**
(**a–d**) corresponds to each AvgPC respectively. The Venn diagrams specify for each AvPC how many significantly associated loci (promising P value in the first stage meta analysis (<5 × 10⁻⁶) and genome wide significant in first and second stage combined analysis (<5 × 10⁻⁸)) are known from previous GIANT analysis on BMI, height or WHR. In the upper right corner of each plot the number of loci is given that are not known from previous GIANT analyses.

See this image and copyright information in PMC

References

1. Wood A. R. et al. Defining the role of common variation in the genomic and biological architecture of adult human height. Nat. Genet. 46, 1173–1186 (2014). - PMC - PubMed
1. Locke A. E. et al. Genetic studies of body mass index yield new insights for obesity biology. Nature 518, 197–206 (2015). - PMC - PubMed
1. Lango Allen H. et al. Hundreds of variants clustered in genomic loci and biological pathways affect human height. Nature 467, 832–838 (2010). - PMC - PubMed
1. Shungin D. et al. New genetic loci link adipose and insulin biology to body fat distribution. Nature 518, 187–196 (2015). - PMC - PubMed
1. Liu C. T. et al. Genome-wide association of body fat distribution in African ancestry populations suggests new loci. PLoS. Genet. 9, e1003681 (2013). - PMC - PubMed

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

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

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