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Nat Commun. 2017 Apr 26;8:14977. doi: 10.1038/ncomms14977.

Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits.

Justice AE1, Winkler TW2, Feitosa MF3, Graff M1, Fisher VA4, Young K1, Barata L3, Deng X4, Czajkowski J3, Hadley D5,6, Ngwa JS4,7, Ahluwalia TS8,9, Chu AY10,11, Heard-Costa NL10,12, Lim E4, Perez J4, Eicher JD13, Kutalik Z14,15,16, Xue L4, Mahajan A17, Renström F18,19, Wu J4, Qi Q20, Ahmad S11,19,21, Alfred T22,23, Amin N24, Bielak LF25, Bonnefond A26, Bragg J27,28, Cadby G29, Chittani M30, Coggeshall S31, Corre T14,15,16, Direk N32,33, Eriksson J34, Fischer K35, Gorski M2,36, Neergaard Harder M8, Horikoshi M17,37, Huang T21,38, Huffman JE13,39, Jackson AU28, Justesen JM8, Kanoni S40, Kinnunen L41, Kleber ME42, Komulainen P43, Kumari M44,45, Lim U46, Luan J47, Lyytikäinen LP48,49, Mangino M50,51, Manichaikul A52, Marten J39, Middelberg RPS53, Müller-Nurasyid M54,55,56, Navarro P39, Pérusse L57,58, Pervjakova N35,59, Sarti C60, Smith AV61,62, Smith JA25, Stančáková A63, Strawbridge RJ64,65, Stringham HM28, Sung YJ66, Tanaka T67, Teumer A68, Trompet S69,70, van der Laan SW71, van der Most PJ72, Van Vliet-Ostaptchouk JV73, Vedantam SL74,75, Verweij N76, Vink JM77,78, Vitart V39, Wu Y79, Yengo L26, Zhang W80,81, Hua Zhao J47, Zimmermann ME2, Zubair N82, Abecasis GR28, Adair LS83, Afaq S80,81, Afzal U80,81, Bakker SJL84, Bartz TM31,85, Beilby J86,87,88, Bergman RN89, Bergmann S15,16, Biffar R90, Blangero J91, Boerwinkle E92, Bonnycastle LL93, Bottinger E22,94, Braga D30, Buckley BM95, Buyske S96,97, Campbell H98, Chambers JC81,80,99, Collins FS93, Curran JE91, de Borst GJ100, de Craen AJM70, de Geus EJC77,101, Dedoussis G102, Delgado GE42, den Ruijter HM71, Eiriksdottir G61, Eriksson AL34, Esko T35,74,75, Faul JD103, Ford I104, Forrester T105, Gertow K64,65, Gigante B106, Glorioso N107, Gong J82, Grallert H108,109,110, Grammer TB42, Grarup N8, Haitjema S71, Hallmans G111, Hamsten A64,65, Hansen T8, Harris TB112, Hartman CA113, Hassinen M43, Hastie ND39, Heath AC114, Hernandez D115, Hindorff L116, Hocking LJ117,118, Hollensted M8, Holmen OL119, Homuth G120, Jan Hottenga J77, Huang J121, Hung J122,123, Hutri-Kähönen N124,125, Ingelsson E126,127,128, James AL86,122,129, Jansson JO130, Jarvelin MR131,132,133,134, Jhun MA25, Jørgensen ME9, Juonala M135,136, Kähönen M137,138, Karlsson M139, Koistinen HA41,140,141, Kolcic I142, Kolovou G143, Kooperberg C82, Krämer BK42, Kuusisto J144, Kvaløy K145, Lakka TA43,146, Langenberg C47, Launer LJ112, Leander K106, Lee NR147,148, Lind L149, Lindgren CM17,150, Linneberg A151,152,153, Lobbens S26, Loh M80,154, Lorentzon M34, Luben R155, Lubke G156, Ludolph-Donislawski A54,157, Lupoli S30, Madden PAF114, Männikkö R43, Marques-Vidal P158, Martin NG53, McKenzie CA105, McKnight B31,85,159, Mellström D34, Menni C50, Montgomery GW160, Musk AB86,161,162, Narisu N93, Nauck M163, Nolte IM72, Oldehinkel AJ113, Olden M2, Ong KK47, Padmanabhan S118,164, Peyser PA25, Pisinger C165,166, Porteous DJ118,167, Raitakari OT168,169, Rankinen T170, Rao DC66,114,171, Rasmussen-Torvik LJ172, Rawal R108,109, Rice T66,114, Ridker PM11,173, Rose LM11, Bien SA82, Rudan I98, Sanna S174, Sarzynski MA170, Sattar N175, Savonen K43, Schlessinger D176, Scholtens S72, Schurmann C22,23, Scott RA47, Sennblad B64,65,177, Siemelink MA71, Silbernagel G178, Slagboom PE179, Snieder H72, Staessen JA180,181, Stott DJ182, Swertz MA183, Swift AJ93, Taylor KD184,185, Tayo BO186, Thorand B109,110, Thuillier D26, Tuomilehto J187,188,189, Uitterlinden AG190,32, Vandenput L34, Vohl MC58,191, Völzke H68, Vonk JM72, Waeber G158, Waldenberger M108,109, Westendorp RGJ192, Wild S98, Willemsen G77, Wolffenbuttel BHR73, Wong A193, Wright AF39, Zhao W25, Zillikens MC190, Baldassarre D194,195, Balkau B196, Bandinelli S197, Böger CA36, Boomsma DI77, Bouchard C170, Bruinenberg M198, Chasman DI11,199, Chen YD200, Chines PS93, Cooper RS186, Cucca F174,201, Cusi D202, Faire U106, Ferrucci L67, Franks PW19,21,203, Froguel P26,204, Gordon-Larsen P83,205, Grabe HJ206,207, Gudnason V61,62, Haiman CA208, Hayward C39,118, Hveem K145, Johnson AD13, Wouter Jukema J69,209,210, Kardia SLR25, Kivimaki M45, Kooner JS211,81,99, Kuh D193, Laakso M144, Lehtimäki T48,49, Marchand LL46, März W212,213, McCarthy MI37,17,214, Metspalu A35, Morris AP17,215, Ohlsson C34, Palmer LJ216, Pasterkamp G71,217, Pedersen O8, Peters A109,110, Peters U82, Polasek O98,142, Psaty BM218,219,220, Qi L21,221, Rauramaa R43,222, Smith BH118,223, Sørensen TIA8,224,225, Strauch K54,157, Tiemeier H226, Tremoli E194,195, van der Harst P76,183,227, Vestergaard H8,9, Vollenweider P158, Wareham NJ47, Weir DR103, Whitfield JB53, Wilson JF39,98, Tyrrell J228,229, Frayling TM230, Barroso I231,232,233, Boehnke M28, Deloukas P40,231,234, Fox CS10, Hirschhorn JN74,75,235, Hunter DJ21,75,236,237, Spector TD50, Strachan DP5,238, van Duijn CM24,239,240, Heid IM2,241, Mohlke KL79, Marchini J242, Loos RJF22,23,47,243,244, Kilpeläinen TO8,47,245, Liu CT4, Borecki IB3, North KE1, Cupples LA4,10.

Author information

1
Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
2
Department of Genetic Epidemiology, Institute of Epidemiology and Preventive Medicine, University of Regensburg, D-93053 Regensburg, Germany.
3
Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine; St. Louis, Missouri, 63108 USA.
4
Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts 02118, USA.
5
Population Health Research Institute, St. George's, University of London, London, SW17 0RE, UK.
6
TransMed Systems, Inc., Cupertino, California 95014, USA.
7
Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore Maryland, USA.
8
The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
9
Steno Diabetes Center, Gentofte, Denmark.
10
NHLBI Framingham Heart Study, Framingham, Massachusetts, 01702 USA.
11
Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts USA.
12
Department of Neurology, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
13
Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, The Framingham Heart Study, Framingham, Massachusetts, USA.
14
Institute of Social and Preventive Medicine (IUMSP), Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
15
Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
16
Swiss instititute of Bioinformatics.
17
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
18
Department of Biobank Research, Umeå University, Umeå, Sweden.
19
Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, SE-205 02 Malmö, Sweden.
20
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, USA.
21
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, USA.
22
The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, USA.
23
The Genetics of Obesity and Related Metabolic Traits Program, Icahn School of Medicine at Mount Sinai, New York, USA.
24
Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam 3015GE, The Netherlands.
25
Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan, USA.
26
University of Lille, CNRS, Institut Pasteur of Lille, UMR 8199 - EGID, Lille, France.
27
Internal Medicine - Nephrology, University of Michigan, Ann Arbor, Michigan, USA.
28
Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA.
29
Centre for Genetic Origins of Health and Disease, University of Western Australia, Crawley, Australia.
30
Department of Health Sciences, University of Milan,Via A. Di Rudiní, 8 20142, Milano, Italy.
31
Department of Biostatistics, University of Washington, Seattle, Washington 98195, USA.
32
Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
33
Department of Psychiatry, Dokuz Eylul University, Izmir, Turkey.
34
Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
35
Estonian Genome Center, University of Tartu, Tartu 51010, Estonia.
36
Department of Nephrology, University Hospital Regensburg, Regensburg, Germany.
37
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UK.
38
Epidemiology Domain, Saw Swee Hock School of Public Health, National University of Singapore, Singapore 117549, Singapore.
39
MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, Scotland.
40
William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
41
Department of Health, National Institute for Health and Welfare, Helsinki, FI-00271 Finland.
42
Vth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
43
Kuopio Research Institute of Exercise Medicine, Kuopio, Finland.
44
ISER, University of Essex, Colchester CO43SQ, UK.
45
Department of Epidemiology and Public Health, UCL, London, WC1E 6BT, UK.
46
Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii 96813, USA.
47
MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge CB2 0QQ, UK.
48
Department of Clinical Chemistry, Fimlab Laboratories, Tampere 33520, Finland.
49
Department of Clinical Chemistry, Faculty of Medicine and Life Sciences, University of Tampere, Tampere 33014, Finland.
50
Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
51
NIHR Biomedical Research Centre at Guy's and St. Thomas' Foundation Trust, London, UK.
52
Center for Public Health Genomics and Biostatistics Section, Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia 22903, USA.
53
Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
54
Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, D-85764 Neuherberg, Germany.
55
Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians-Universität, D-81377 Munich, Germany.
56
DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany.
57
Department of Kinesiology, Faculty of Medicine, Université Laval, Québec, Canada.
58
Institute of Nutrition and Functional Foods, Université Laval, Québec, Canada.
59
Department of Biotechnology, Institute of Molecular and Cell Biology, University of Tartu, Tartu 51010, Estonia.
60
Department of Social and Health Care, City of Helsinki, Helsinki, Finland.
61
Icelandic Heart Association, Kopavogur, Iceland.
62
Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
63
Department of Medicine, Institute of Clinical Medicine, University of Eastern Finland, 70210 Kuopio, Finland.
64
Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
65
Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden.
66
Division of Biostatistics, Washington University School of Medicine, St Louis, Missouri, USA.
67
Translational Gerontology Branch, National Institute on Aging, Baltimore Maryland, USA.
68
Institute for Community Medicine, University Medicine Greifswald, Germany.
69
Department of Cardiology, Leiden University Medical Center, The Netherlands.
70
Department of Gerontology and Geriatrics, Leiden University Medical Center, The Netherlands.
71
Laboratory of Experimental Cardiology, Department of Cardiology, Division Heart &Lungs, UMC Utrecht, The Netherlands.
72
Department of Epidemiology, University of Groningen, University Medical Center Groningen, The Netherlands.
73
Department of Endocrinology, University of Groningen, University Medical Center Groningen, The Netherlands.
74
Divisions of Endocrinology and Genetics and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston Massachusetts 02115, USA.
75
Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.
76
Department of Cardiology, University Medical Center Groningen, University of Groningen, The Netherlands.
77
Department of Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands.
78
Behavioural Science Institute, Radboud University, Nijmegen, The Netherlands.
79
Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
80
Dept Epidemiology and Biostatistics, School of Public Health, Imperical College London, UK.
81
Cardiology, Ealing Hospital NHS Trust, Middlesex, UK.
82
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle Washington USA.
83
Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
84
Department of Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
85
Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington 98101, USA.
86
Busselton Population Medical Research Institute, Nedlands, Western Australia 6009, Australia.
87
PathWest Laboratory Medicine of WA, Sir Charles Gairdner Hospital, Nedlands, Western Australia 6009, Australia.
88
School of Pathology and Laboraty Medicine, The University of Western Australia, 35 Stirling Hwy, Crawley, Western Australia 6009, Australia.
89
Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
90
Clinic for Prosthetic Dentistry, Gerostomatology and Material Science, University Medicine Greifswald, Germany.
91
South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley, Brownsville, Texas, USA.
92
Human Genetics Center, The University of Texas Health Science Center, PO Box 20186, Houston, Texas 77225, USA.
93
Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland 20892, USA.
94
Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, USA.
95
Department of Pharmacology and Therapeutics, University College Cork, Ireland.
96
Department of Genetics, Rutgers University, Piscataway, New Jersey 08854, USA.
97
Department of Statistics and Biostatistics, Rutgers University, Piscataway, New Jersey 08854, USA.
98
Usher Institute for Population Health Sciences and Informatics, The University of Edinburgh, Scotland, UK.
99
Imperial College Healthcare NHS Trust, London, UK.
100
Department of Vascular Surgery, Division of Surgical Specialties, UMC Utrecht, The Netherlands.
101
EMGO+ Institute Vrije Universiteit &Vrije Universiteit Medical Center.
102
Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece.
103
Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, Michigan, USA.
104
Robertson Centre for Biostatistics, University of Glasgow, UK.
105
Tropical Metabolism Research Unit, Tropical Medicine Research Institute, University of the West Indies, Mona, JMAAW15 Jamaica.
106
Unit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
107
Hypertension and Related Disease Centre, AOU-University of Sassari.
108
Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, D-85764 Neuherberg, Germany.
109
Institute of Epidemiology II, Helmholtz Zentrum München - German Research Center for Environmental Health, D-85764 Neuherberg, Germany.
110
German Center for Diabetes Research, D-85764 Neuherberg, Germany.
111
Department of Public Health and Clinical Medicine, Section for Nutritional Research, Umeå University, Umeå, Sweden.
112
Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
113
Interdisciplinary Center Psychopathology and Emotion Regulation (ICPE), University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
114
Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.
115
Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA.
116
Division of Genomic Medicine, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
117
Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
118
Generation Scotland, Centre for Genomic and Experimental Medicine, University of Edinburgh, Edinburgh, Scotland.
119
St. Olav Hospital, Trondheim University Hospital, Trondheim, Norway.
120
Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Germany.
121
Department of Human Genetics, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
122
School of Medicine and Pharmacology, The University of Western Australia, 25 Stirling Hwy, Crawley, Western Australia 6009, Australia.
123
Department of Cardiovascular Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia 6009, Australia.
124
Department of Pediatrics, Tampere University Hospital, Tampere 33521, Finland.
125
Department of Pediatrics, Faculty of Medicine and Life Sciences, University of Tampere, Tampere 33014, Finland.
126
Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala, 751 85, Sweden.
127
Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
128
Science for Life Laboratory, Uppsala University, Uppsala, 750 85, Sweden.
129
Department of Pulmonary Physiology and Sleep Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia 6009, Australia.
130
Department of Physiology, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
131
Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment &Health, School of Public Health, Imperial College London, UK.
132
Center for Life Course Epidemiology, Faculty of Medicine, University of OuluP.O.Box 5000, FI-90014, Finland.
133
Biocenter Oulu, University of Oulu, Finland.
134
Unit of Primary Care, Oulu University Hospital, Kajaanintie 50, P.O.Box 20, FI-90220, 90029 Oulu, Finland.
135
Department of Medicine, University of Turku, Turku 20520 Finland.
136
Division of Medicine, Turku University Hospital, Turku 20521, Finland.
137
Department of Clinical Physiology, Tampere University Hospital, Tampere 33521, Finland.
138
Department of Clinical Physiology, Faculty of Medicine and Life Sciences, University of Tampere, Tampere 33014, Finland.
139
Clinical and Molecular Osteoporosis Research Unit, Department of Orthopedics and Clinical Sciences, Skåne University Hospital, Lund University, Malmö, Sweden.
140
Department of Medicine and Abdominal Center: Endocrinology, University of Helsinki and Helsinki University Central Hospital, Helsinki, FI-00029 Finland.
141
Minerva Foundation Institute for Medical Research, Biomedicum 2U, Helsinki, FI-00290 Finland.
142
Department of Public Health, Faculty of Medicine, University of Split, Croatia.
143
Department of Cardiology, Onassis Cardiac Surgery Center, Athens, Greece.
144
Department of Medicine, University of Eastern Finland and Kuopio University Hospital, 70210 Kuopio, Finland.
145
HUNT Research Centre, Department of Public Health and Nursing, Norwegian University of Science and Technology, 7600 Levanger, Norway.
146
Institute of Biomedicine/Physiology, University of Eastern Finland, Kuopio Campus, Finland.
147
USC-Office of Population Studies Foundation, Inc., University of San Carlos, Cebu City 6000, Philippines.
148
Department of Anthropology, Sociology and History, University of San Carlos, Cebu City 6000, Philippines.
149
Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala 751 85, Sweden.
150
Li Ka Shing Centre for Health Information and Discovery, The Big Data Institute, University of Oxford, Oxford OX3 7BN, UK.
151
Research Centre for Prevention and Health, the Capital Region of Denmark, Copenhagen, Denmark.
152
Department of Clinical Experimental Research, Rigshospitalet, Glostrup, Denmark.
153
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
154
Translational Laboratory in Genetic Medicine (TLGM), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos, Level 5, Singapore 138648, Singapore.
155
Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
156
Department of Psychology, University of Notre Dame, Notre Dame, USA.
157
Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-Universität, D-81377 Munich, Germany.
158
Department of Medicine, Internal Medicine, Lausanne university hospital (CHUV), Lausanne, Switzerland.
159
Program in Biostatistics and Biomathematics, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
160
Molecular Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
161
School of Population Health, The University of Western Australia, 35 Stirling Hwy, Crawley, Western Australia 6009, Australia.
162
Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia 6009, Australia.
163
Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Germany.
164
Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Scotland.
165
Research Center for Prevention and Health, Glostrup Hospital, Glostrup Denmark.
166
Department of Public Health, Faculty of Health Sciences, University of Copenhagen, Denmark.
167
Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh.
168
Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku 20521, Finland.
169
Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku 20520, Finland.
170
Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.
171
Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, USA.
172
Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
173
Division of Cardiology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
174
Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale Delle Ricerche (CNR), Cittadella Universitaria di Monserrato, 09042, Monserrato, Italy.
175
BHF Glasgow Cardiovascular Research Centre, Faculty of Medicine, Glasgow, UK.
176
Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.
177
Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden.
178
Division of Angiology, Department of Internal Medicine, Medical University of Graz, Austria.
179
Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
180
Research Unit Hypertension and Cardiovascular Epidemiology, Department of Cardiovascular Science , University of Leuven, Campus Sint Rafael, Kapucijnenvoer 35, Leuven; Belgium.
181
R&D VitaK Group, Maastricht University, Brains Unlimited Building, Oxfordlaan 55, Maastricht, The Netherlands.
182
Institute of Cardiovascular and Medical Sciences, Faculty of Medicine, University of Glasgow, UK.
183
Department of Genetics, University of Groningen, University Medical Center Groningen, The Netherlands.
184
Center for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor/UCLA Medical Center, Torrance, California, USA.
185
Department of Pediatrics, University of California Los Angeles, Los Angeles, California, USA.
186
Department of Public Health Sciences, Stritch School of Medicine, Loyola University of Chicago, Maywood, Illinois 61053, USA.
187
Research Division, Dasman Diabetes Institute, Dasman, Kuwait.
188
Department of Neurosciences and Preventive Medicine, Danube-University Krems, 3500 Krems, Austria.
189
Saudi Diabetes Research Group, King Abdulaziz University, Jeddah, Saudi Arabia.
190
Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
191
School of Nutrition, Université Laval, Québec, Canada.
192
Department of Public Health, and Center for Healthy Ageing, University of Copenhagen, Denmark.
193
MRC Unit for Lifelong Health and Ageing at UCL, 33 Bedford Place, London, WC1B 5JU, UK.
194
Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Milan, Italy.
195
Centro Cardiologico Monzino, IRCCS, Milan, Italy.
196
Inserm U-1018, CESP, 94807 Villejuif cedex France.
197
Geriatric Unit, Azienda USL Toscana centro, Florence Italy.
198
Lifelines Cohort Study, PO Box 30001, 9700 RB Groningen, The Netherlands.
199
Division of Genetics, Brigham and Women's Hospital, Boston, Massachusetts, USA.
200
Institute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute and Department of Pediatrics, Harbor-UCLA, Torrance, California 90502, USA.
201
Dipartimento di Scienze Biomediche, Universita' degli Studi di Sassari, Sassari, Italy.
202
Sanipedia srl, Bresso (Milano), Italy and Institute of Biomedical Technologies National Centre of Research Segrate, Milano, Italy.
203
Department of Public Health &Clinical Medicine, Umeå University, Umeå, Sweden.
204
Department of Genomics of Common Disease, Imperial College London, London, UK.
205
Carolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill North Carolina, 27516, USA.
206
Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Germany.
207
German Center for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Germany.
208
Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, 90089, USA.
209
Durrer Center for Cardiogenetic Research, Amsterdam, The Netherlands.
210
Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands.
211
Faculty of Med, National Heart &Lung Institute, Cardiovascular Science, Hammersmith Campus, Hammersmith Hospital, Hammersmith Campus, Imperial College London, UK.
212
Synlab Academy, Synlab Services GmbH, Mannheim, Germany.
213
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
214
Oxford National Institute for Health Research (NIHR) Biomedical Research Centre, Churchill Hospital, Oxford, UK.
215
Department of Biostatistics, University of Liverpool, Liverpool L69 3GL, UK.
216
School of Public Health, University of Adelaide, Adelaide, South Australia, Australia.
217
Laboratory of Clinical Chemistry and Hematology, Division Laboratories &Pharmacy, UMC Utrecht, The Netherlands.
218
Department of Medicine, University of Washington, Seattle, Washington 98195, USA.
219
Department of Epidemiology, University of Washington, Seattle, Washington 98101, USA.
220
Group Health Research Institute, Group Health Cooperative, Seattle, Washington 98101, USA.
221
Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana, USA.
222
Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland.
223
Division of Population Health Sciences, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD2 4RB, Scotland.
224
Department of Clinical Epidemiology (formerly Institute of Preventive Medicine), Bispebjerg and Frederiksberg Hospital (2000 Frederiksberg), The Capital Region, Copenhagen, Denmark.
225
MRC Integrative Epidemiology Unit, Bristol University, Bristol, UK.
226
Department of Psychiatry Erasmus Medical Center, Rotterdam, The Netherlands.
227
Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, The Netherlands.
228
Genetics of Complex Traits, University of Exeter Medical School, RILD Building University of Exeter, Exeter, EX2 5DW, UK.
229
European Centre for Environment and Human Health, University of Exeter Medical School, The Knowledge Spa, Truro TR1 3HD, UK.
230
Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter EX1 2LU, UK.
231
Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
232
NIHR Cambridge Biomedical Research Centre, Level 4, Institute of Metabolic Science Box 289 Addenbrooke's Hospital Cambridge CB2 OQQ, UK.
233
University of Cambridge Metabolic Research Laboratories, Level 4, Institute of Metabolic Science Box 289 Addenbrooke's Hospital Cambridge CB2 OQQ, UK.
234
Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia.
235
Department of Genetics, Harvard Medical School, Boston Massachusetts 02115, USA.
236
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, USA.
237
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
238
Division of Population Health Sciences and Education, St George's, University of London, London SW17 0RE, UK.
239
Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA). Leiden, The Netherlands.
240
Center for Medical Systems Biology, Leiden, The Netherlands.
241
Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg 85764, Germany.
242
Department of Statistics, University of Oxford, Oxford, UK.
243
Mount Sinai School of Medicine, New York 10029, USA.
244
The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, USA.
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Department of Preventive Medicine, The Icahn School of Medicine at Mount Sinai, New York, 10029, USA.

Abstract

Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.

PMID:
28443625
PMCID:
PMC5414044
DOI:
10.1038/ncomms14977
[Indexed for MEDLINE]
Free PMC Article

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