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PLoS Genet. 2017 Apr 27;13(4):e1006528. doi: 10.1371/journal.pgen.1006528. eCollection 2017 Apr.

Genome-wide physical activity interactions in adiposity - A meta-analysis of 200,452 adults.

Graff M1, Scott RA2, Justice AE1, Young KL1,3, Feitosa MF4, Barata L4, Winkler TW5, Chu AY6,7, Mahajan A8, Hadley D9, Xue L6,10, Workalemahu T11, Heard-Costa NL6,12, den Hoed M2,13, Ahluwalia TS14,15, Qi Q16, Ngwa JS17, Renström F18,19, Quaye L20, Eicher JD21, Hayes JE22,23, Cornelis M11,24,25, Kutalik Z26,27, Lim E10, Luan J2, Huffman JE6,28, Zhang W29,30, Zhao W31, Griffin PJ10, Haller T32, Ahmad S18, Marques-Vidal PM33, Bien S34, Yengo L35, Teumer A36,37, Smith AV38,39, Kumari M40, Harder MN14, Justesen JM14, Kleber ME41,42, Hollensted M14, Lohman K43, Rivera NV44, Whitfield JB45, Zhao JH2, Stringham HM46, Lyytikäinen LP47,48, Huppertz C49,50,51, Willemsen G49,50, Peyrot WJ52, Wu Y53, Kristiansson K54,55, Demirkan A56,57, Fornage M58,59, Hassinen M60, Bielak LF31, Cadby G61, Tanaka T62, Mägi R32, van der Most PJ63, Jackson AU46, Bragg-Gresham JL46, Vitart V28, Marten J28, Navarro P28, Bellis C64,65, Pasko D66, Johansson Å67, Snitker S68, Cheng YC68,69, Eriksson J70, Lim U71, Aadahl M72,73, Adair LS74, Amin N56, Balkau B75, Auvinen J76,77, Beilby J78,79,80, Bergman RN81, Bergmann S27,82, Bertoni AG83,84, Blangero J85, Bonnefond A35, Bonnycastle LL86, Borja JB87,88, Brage S2, Busonero F89, Buyske S90,91, Campbell H92, Chines PS86, Collins FS86, Corre T27,82, Smith GD93, Delgado GE41, Dueker N94, Dörr M37,95, Ebeling T96,97, Eiriksdottir G38, Esko T32,98,99,100, Faul JD101, Fu M68, Færch K15, Gieger C102,103,104, Gläser S95, Gong J34, Gordon-Larsen P3,74, Grallert H102,104,105, Grammer TB41, Grarup N14, van Grootheest G52, Harald K54, Hastie ND28, Havulinna AS54, Hernandez D106, Hindorff L107, Hocking LJ108,109, Holmens OL110, Holzapfel C102,111, Hottenga JJ49,112, Huang J113, Huang T11, Hui J78,79,114, Huth C104,105, Hutri-Kähönen N115,116, James AL78,117,118, Jansson JO119, Jhun MA31, Juonala M120,121, Kinnunen L54, Koistinen HA54,122,123, Kolcic I124, Komulainen P60, Kuusisto J125, Kvaløy K126, Kähönen M127,128, Lakka TA60,129, Launer LJ130, Lehne B29, Lindgren CM8,131,132, Lorentzon M70,133, Luben R134, Marre M135,136, Milaneschi Y52, Monda KL1,137, Montgomery GW45, De Moor MHM50,138, Mulas A89,139, Müller-Nurasyid M103,140,141, Musk AW78,114,142, Männikkö R60, Männistö S54, Narisu N86, Nauck M37,143, Nettleton JA59, Nolte IM63, Oldehinkel AJ144, Olden M5, Ong KK2, Padmanabhan S109,145, Paternoster L93, Perez J10, Perola M54,55,146, Peters A104,105,141, Peters U34, Peyser PA31, Prokopenko I147, Puolijoki H148, Raitakari OT149,150, Rankinen T151, Rasmussen-Torvik LJ24, Rawal R102,103,104, Ridker PM7,152, Rose LM7, Rudan I92, Sarti C153, Sarzynski MA151, Savonen K60, Scott WR29, Sanna S89, Shuldiner AR68,69, Sidney S154, Silbernagel G155, Smith BH109,156, Smith JA31, Snieder H63, Stančáková A125, Sternfeld B154, Swift AJ86, Tammelin T157, Tan ST158, Thorand B104,105, Thuillier D35, Vandenput L70, Vestergaard H14,15, van Vliet-Ostaptchouk JV159, Vohl MC160,161, Völker U37,162, Waeber G33, Walker M163, Wild S164, Wong A165, Wright AF28, Zillikens MC166, Zubair N34, Haiman CA167, Lemarchand L71, Gyllensten U67, Ohlsson C70, Hofman A168,169, Rivadeneira F166,168,169, Uitterlinden AG166,168, Pérusse L160,170, Wilson JF28,92, Hayward C28, Polasek O92,124, Cucca F89,139, Hveem K126, Hartman CA171, Tönjes A172, Bandinelli S173, Palmer LJ174, Kardia SLR31, Rauramaa R60,175, Sørensen TIA14,73,93,176, Tuomilehto J54,177,178, Salomaa V54, Penninx BWJH52, de Geus EJC49,50, Boomsma DI49,112, Lehtimäki T47,48, Mangino M20,179, Laakso M125, Bouchard C151, Martin NG45, Kuh D165, Liu Y83, Linneberg A72,180,181, März W41,182,183, Strauch K103,184, Kivimäki M185, Harris TB186, Gudnason V38,39, Völzke H36,37, Qi L11, Järvelin MR29,76,77,187,188, Chambers JC29,30,189, Kooner JS30,158,189, Froguel P35,190, Kooperberg C34, Vollenweider P33, Hallmans G19, Hansen T14, Pedersen O14, Metspalu A32, Wareham NJ2, Langenberg C2, Weir DR101, Porteous DJ109,191, Boerwinkle E59, Chasman DI7,100,152; CHARGE Consortium; EPIC-InterAct Consortium; PAGE Consortium, Abecasis GR46, Barroso I192,193,194, McCarthy MI8,195,196, Frayling TM66, O'Connell JR68, van Duijn CM56,169,197, Boehnke M46, Heid IM5, Mohlke KL53, Strachan DP198, Fox CS21, Liu CT10, Hirschhorn JN99,100,199, Klein RJ23, Johnson AD6,21, Borecki IB4, Franks PW11,18,200, North KE201, Cupples LA6,10, Loos RJF2,202,203,204, Kilpeläinen TO2,14,204.

Author information

1
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
2
MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom.
3
Carolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
4
Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, United States of America.
5
Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany.
6
National Heart, Lung, and Blood Institute, Framingham Heart Study, Framingham, Massachusetts, United States of America.
7
Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
8
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
9
Division of Population Health Sciences and Education, St. George's, University of London, London, United Kingdom.
10
Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, United States of America.
11
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America.
12
Department of Neurology, Boston University School of Medicine, Boston, Massachusetts, United States of America.
13
Department of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
14
Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
15
Steno Diabetes Center, Gentofte, Denmark.
16
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, United States of America.
17
Howard University, Department of Internal Medicine, Washington DC, United States of America.
18
Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden.
19
Department of Biobank Research, Umeå University, Umeå, Sweden.
20
Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom.
21
Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, The Framingham Heart Study, Framingham, Massachusetts, United States of America.
22
Cell and Developmental Biology Graduate Program, Weill Cornell Graduate School of Medical Sciences, Cornell University, New York, New York, United States of America.
23
Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
24
Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America.
25
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
26
Institute of Social and Preventive Medicine, Lausanne University Hospital, Lausanne, Switzerland.
27
Swiss Institute of Bioinformatics, Lausanne, Switzerland.
28
MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom.
29
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
30
Department of Cardiology, Ealing Hospital HNS Trust, Middlesex, United Kingdom.
31
Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan, United States of America.
32
Estonian Genome Center, University of Tartu, Tartu, Estonia.
33
Department of Internal Medicine, Internal Medicine, Lausanne University Hospital, Lausanne, Switzerland.
34
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
35
University of Lille, CNRS, Institut Pasteur de Lille, UMR 8199 - EGID, Lille, France.
36
Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
37
DZHK (German Center for Cardiovascular Research), partner site Greifswald, Greifswald, Germany.
38
Icelandic Heart Association, Kopavogur, Iceland.
39
Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
40
ISER, University of Essex, Colchester, Essex, United Kingdom.
41
Vth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
42
Institute of Nutrition, Friedrich Schiller University Jena, Jena, Germany.
43
Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.
44
Karolinska Institutet, Respiratory Unit, Department of Medicine Solna, Stockholm, Sweden.
45
Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
46
Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, United States of America.
47
Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland.
48
Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere, Finland.
49
Department of Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands.
50
EMGO+ Institute, Vrije Universiteit & VU University Medical Center, Amsterdam, The Netherlands.
51
Department of Public and Occupational Health, VU University Medical Center, Amsterdam, The Netherlands.
52
Department of Psychiatry, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, VU University Medical Center/GGZ InGeest, Amsterdam, The Netherlands.
53
Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, United States of America.
54
National Institute for Health and Welfare, Department of Health, Helsinki, Finland.
55
Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
56
Genetic Epidemiology Unit, Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.
57
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
58
Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, United States of America.
59
Division of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas Health Science Center at Houston, Houston, Texas, United States of America.
60
Kuopio Research Institute of Exercise Medicine, Kuopio, Finland.
61
Centre for Genetic Origins of Health and Disease, University of Western Australia, Crawley, Western Australia, Australia.
62
Translational Gerontology Branch, National Institute on Aging, Baltimore, Maryland, United States of America.
63
Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
64
Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research of Singapore, Singapore.
65
Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.
66
Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, United Kingdom.
67
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
68
Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
69
Veterans Affairs Maryland Health Care System, University of Maryland, Baltimore, Maryland, United States of America.
70
Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
71
Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, United States of America.
72
Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark.
73
Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
74
Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
75
INSERM U-1018, CESP, Renal and Cardiovascular Epidemiology, UVSQ-UPS, Villejuif, France.
76
Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland.
77
Unit of Primary Care, Oulu University Hospital, Oulu, Finland.
78
Busselton Population Medical Research Institute, Nedlands, Western Australia, Australia.
79
PathWest Laboratory Medicine of WA, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
80
School of Pathology and Laboratory Medicine, The University of Western Australia, Crawley, Western Australia, Australia.
81
Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
82
Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland.
83
Department of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.
84
Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.
85
Texas Biomedical Research Institute, San Antonio, Texas, United States of America.
86
Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, United States of America.
87
USC-Office of Population Studies Foundation, Inc., University of San Carlos, Cebu City, Philippines.
88
Department of Nutrition and Dietetics, University of San Carlos, Cebu City, Philippines.
89
Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale Delle Ricerche (CNR), Cittadella Universitaria di Monserrato, Monserrato, Italy.
90
Department of Genetics, Rutgers University, Piscataway, New Jersey, United States of America.
91
Department of Statistics and Biostatistics, Rutgers University, Piscataway, New Jersey, United States of America.
92
Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, Edinburgh, Scotland.
93
MRC Integrative Epidemiology Unit & School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
94
University of Maryland School of Medicine, Department of Epidemiology & Public Health, Baltimore, Maryland, United States of America.
95
Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany.
96
Department of Medicine, Oulu University Hospital, Oulu, Finland.
97
Institute of Clinical Medicine, Faculty of Medicine, University of Oulu, Oulu, Finland.
98
Division of Endocrinology, Boston Children's Hospital, Boston, Massachusetts, United States of America.
99
Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America.
100
Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts, United States of America.
101
Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, Michigan, United States of America.
102
Research Unit of Molecular Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
103
Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
104
Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
105
German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
106
Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, United States of America.
107
Division of Genomic Medicine, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
108
Musculoskeletal Research Programme, Division of Applied Medicine, University of Aberdeen, Foresterhill, Aberdeen, United Kingdom.
109
Generation Scotland, Centre for Genomic and Experimental Medicine, University of Edinburgh, Edinburgh, United Kingdom.
110
St. Olav Hospital, Trondheim University Hospital, Trondheim, Norway.
111
Institute for Nutritional Medicine, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.
112
NCA Institute, VU University & VU Medical Center, Amsterdam, The Netherlands.
113
Department of Human Genetics, Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
114
School of Population Health, The University of Western Australia, Crawley, Western Australia, Australia.
115
Department of Pediatrics, Tampere University Hospital, Tampere, Finland.
116
Department of Pediatrics, University of Tampere School of Medicine, Tampere, Finland.
117
Department of Pulmonary Physiology and Sleep Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
118
School of Medicine and Pharmacology, The University of Western Australia, Crawley, Western Australia, Australia.
119
Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
120
Department of Medicine, University of Turku, Turku, Finland.
121
Division of Medicine, Turku University Hospital, Turku, Finland.
122
Department of Medicine and Abdominal Center: Endocrinology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
123
Minerva Foundation Institute for Medical Research, Helsinki, Finland.
124
Department of Public Health, Faculty of Medicine, University of Split, Split, Croatia.
125
Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
126
HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway.
127
Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland.
128
Department of Clinical Physiology, University of Tampere School of Medicine, Tampere, Finland.
129
Institute of Biomedicine, Physiology, University of Eastern Finland, Kuopio Campus, Finland.
130
Neuroepidemiology Section, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America.
131
Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America.
132
The Big Data Institute, University of Oxford, Oxford, United Kingdom.
133
Geriatric Medicine, Sahlgrenska University Hospital, Mölndal, Sweden.
134
Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
135
INSERM U-1138, Équipe 2: Pathophysiology and Therapeutics of Vascular and Renal diseases Related to Diabetes, Centre de Recherche des Cordeliers, Paris, France.
136
Department of Endocrinology, Diabetology, Nutrition, and Metabolic Diseases, Bichat Claude Bernard Hospital, Paris, France.
137
Center for Observational Research, Amgen Inc., Thousand Oaks, California, United States of America.
138
Section of Clinical Child and Family Studies, Department of Educational and Family Studies, Vrije Universiteit, Amsterdam, The Netherlands.
139
Dipartimento di Scienze Biomediche, Università degli Studi di Sassari, Sassari, Italy.
140
Department of Medicine I, Ludwig-Maximilians-Universität, Munich, Germany.
141
DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany.
142
Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
143
Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
144
Interdisciplinary Center Psychopathology and Emotion Regulation (ICPE), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
145
Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom.
146
University of Tartu, Estonian Genome Centre, Tartu, Estonia.
147
Genomics of Common Disease, Imperial College London, London, United Kingdom.
148
South Ostrobothnia Central Hospital, Seinäjoki, Finland.
149
Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
150
Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
151
Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana, United States of America.
152
Harvard Medical School, Boston, Massachusetts, United States of America.
153
Social Services and Health Care Department, City of Helsinki, Helsinki, Finland.
154
Division of Research, Kaiser Permanente Northern California, Oakland, California, United States of America.
155
Division of Angiology, Department of Internal Medicine, Medical University Graz, Austria.
156
School of Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, Scotland.
157
LIKES Research Center for Sport and Health Sciences, Jyväskylä, Finland.
158
National Heart and Lung Institute, Imperial College London, United Kingdom.
159
Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
160
Institute of Nutrition and Functional Foods, Quebec, Canada.
161
School of Nutrition, Laval University, Quebec, Canada.
162
Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Germany.
163
Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
164
Centre for Population Health Sciences, Usher Institute for Population Health Sciences and Informatics, Teviot Place, Edinburgh, Scotland.
165
MRC Unit for Lifelong Health and Ageing at UCL, London, United Kingdom.
166
Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
167
Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
168
Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.
169
Netherlands Consortium for Healthy Aging, Leiden University Medical Center, Leiden, The Netherlands.
170
Department of Kinesiology, Laval University, Quebec, Canada.
171
Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
172
University of Leipzig, Medical Department, Leipzig, Germany.
173
Geriatric Unit, Azienda Sanitaria Firenze, Florence, Italy.
174
School of Public Health, University of Adelaide, Adelaide, South Australia, Australia.
175
Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland.
176
Department of Clinical Epidemiology, Bispebjerg and Frederiksberg Hospitals, The Capital Region, Copenhagen, Denmark.
177
Centre for Vascular Prevention, Danube-University Krems, Krems, Austria.
178
Diabetes Research Group, King Abdulaziz University, Jeddah, Saudi Arabia.
179
National Institute for Health Research Biomedical Research Centre at Guy's and St. Thomas' Foundation Trust, London, United Kingdom.
180
Department of Clinical Experimental Research, Rigshospitalet, Glostrup, Denmark.
181
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
182
Synlab Academy, Synlab Services LLC, Mannheim, Germany.
183
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
184
Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany.
185
Department of Epidemiology and Public Health, University College London, London, United Kingdom.
186
Laboratory of Epidemiology and Population Science, National Institute on Aging, Bethesda, Maryland, United States of America.
187
Biocenter Oulu, University of Oulu, Oulu, Finland.
188
MRC-PHE Centre for Environment and Health, Imperial College London, London, United Kingdom.
189
Imperial College Healthcare NHS Trust, London, United Kingdom.
190
Hammersmith Hospital, London, United Kingdom.
191
Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
192
Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
193
NIHR Cambridge Biomedical Research Centre, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, United Kingdom.
194
The University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, United Kingdom.
195
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, United Kingdom.
196
Oxford NIHR Biomedical Research Centre, Oxford, United Kingdom.
197
Center of Medical Systems Biology, Leiden, The Netherlands.
198
Population Health Research Institute, St. George's University of London, London, United Kingdom.
199
Divisions of Endocrinology and Genetics and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts, United States of America.
200
Department of Public Health & Clinical Medicine, Umeå University, Umeå, Sweden.
201
Carolina Center for Genome Sciences, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
202
Genetics of Obesity and Related Metabolic Traits Program, Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
203
The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
204
The Department of Preventive Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.

Abstract

Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.

PMID:
28448500
PMCID:
PMC5407576
DOI:
10.1371/journal.pgen.1006528
[Indexed for MEDLINE]
Free PMC Article

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