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Physical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218,166 adults and 19,268 children.

Tuomas Kilpeläinen 1 Lu Qi 2, * Soren Brage 1 Stephen Sharp 1 Emily Sonestedt 3 Ellen Demerath 4 Tariq Ahmad 5 Samia Mora 6 Marika Kaakinen 7 Camilla Helene Sandholt 8 Christina Holzapfel 9, 10 Christine Autenrieth 11 Elina Hyppönen 12, 13 Stéphane Cauchi 14 Meian He 15 Zoltan Kutalik 16 Meena Kumari 17 Alena Stančáková 18 Karina Meidtner 19 Beverley Balkau 20 Jonathan Tan 21 Massimo Mangino 22 Nicholas Timpson 23 Yiqing Song 24 M Carola Zillikens 25, 26 Kathleen Jablonski 27 Melissa Garcia 28 Stefan Johansson 29, 30 Jennifer Bragg-Gresham 31 Ying Wu 32 Jana van Vliet-Ostaptchouk 33 N Charlotte Onland-Moret 34, 35 Esther Zimmermann 36, 37 Natalia Rivera 38 Toshiko Tanaka 28, 39 Heather Stringham 31 Günther Silbernagel 40 Stavroula Kanoni 41 Mary Feitosa 42 Soren Snitker 43 Jonatan Ruiz 44, 45 Jeffery Metter 28 Maria Teresa Martinez Larrad 46 Mustafa Atalay 47 Maarit Hakanen 48 Najaf Amin 38 Christine Cavalcanti-Proença 14 Anders Grøntved 49 Göran Hallmans 50 John-Olov Jansson 51 Johanna Kuusisto 18 Mika Kähönen 52 Pamela Lutsey 4 John Nolan 53 Luigi Palla 1 Oluf Pedersen 8, 36, 54, 55 Louis Pérusse 56 Frida Renström 2, 3, 56 Robert Scott 1 Dmitry Shungin 3, 56, 57 Ulla Sovio 58 Tuija Tammelin 59, 60 Tapani Rönnemaa 61 Timo Lakka 47 Matti Uusitupa 62 Manuel Serrano Rios 46 Luigi Ferrucci 39 Claude Bouchard 63 Aline Meirhaeghe 64 Mao Fu 65 Mark Walker 66 Ingrid Borecki 42 George Dedoussis 41 Andreas Fritsche 40 Claes Ohlsson 67 Michael Boehnke 31 Stefania Bandinelli 68 Cornelia van Duijn 26, 38, 69 Shah Ebrahim 70 Debbie Lawlor 23 Vilmundur Gudnason 71, 72 Tamara Harris 28 Thorkild Sørensen 36 Karen Mohlke 32 Albert Hofman 26, 38 André Uitterlinden 25, 26, 38 Jaakko Tuomilehto 73, 74, 75 Terho Lehtimäki 76 Olli Raitakari 48, 77 Bo Isomaa 78, 79 Pål Njølstad 30 Jose Florez 80, 81, 82 Simin Liu 83 Andy Ness 84 Timothy Spector 22 E Shyong Tai 85 Philippe Froguel 14, 86 Heiner Boeing 19 Markku Laakso 18 Michael Marmot 87 Sven Bergmann 16 Chris Power 12 Kay-Tee Khaw 88 Daniel Chasman 6 Paul Ridker 6 Torben Hansen 8, 54, 89 Keri Monda 90 Thomas Illig 10 Marjo-Riitta Järvelin 7, 91, 92 Nicholas Wareham 1 Frank Hu 15 Leif Groop 3 Marju Orho-Melander 3 Ulf Ekelund 1 Paul Franks 2, 3, 56, * Ruth Loos 1, *
* Corresponding author
1 Institute of Metabolic Science
2 Departments of Epidemiology and Nutrition
3 Department of Clinical Sciences
4 Division of Epidemiology and Community Health
5 Division of Cardiology
6 Brigham and Women's Hospital [Boston]
7 Institute of Health Sciences and Biocenter Oulu
8 Hagedorn Research Institute
9 ZIEL - Else Kroener Fresenius Centre - Zentralinstitut für Ernährungs und Lebensmittelfors
10 Department of Population Health Sciences
11 EPI - Institute of Epidemiology [Neuherberg]
12 Centre for Paediatric Epidemiology and Biostatistics
13 MRC Centre for Epidemiology of Child Health
14 IBL - Institut de biologie de Lille - UMS 3702
15 Harvard School of Public Health
16 Department of Medical Genetics
17 Department of Epidemiology and Public Health
18 Department of Medicine
19 Department of Epidemiology
20 CESP - Centre de recherche en épidémiologie et santé des populations
21 Department of Epidemiology and Public Health
22 King‘s College London
23 Centre for Causal Analyses in Translational Epidemiology
24 Division of Preventive Medicine
25 Netherlands Genomics Initiative
26 Department of Internal Medicine
27 The Biostatistics Center
28 NIA - National Institute on Aging [Bethesda, USA]
29 Mental Health Sciences Unit
30 Department of Clinical Medicine
31 Department of Biostatistics and Center for Statistical Genetics
32 Department of Genetics
33 Molecular Genetics Section
34 Complex Genetics Section
35 Julius Center for Health Sciences and Primary Care
36 Institute of Preventive Medicine
37 Department of Biomedical Sciences [Copenhagen]
38 Genetic Epidemiology Unit
39 Medstar Research Institute
40 Division of Endocrinology, Diabetology, Nephrology, Vascular Disease, and Clinical Chemistry
41 Department of Nutrition-Dietetics
42 Division of Statistical Genomics
43 University of Maryland School of Medicine
44 Unit for Preventive Nutrition
45 Department of Physical Education and Sport
46 Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas
47 Department of Physiology
48 The Research Centre of Applied and Preventive Cardiovascular Medicine
49 Institute of Sport Science and Clinical Biomechanics
50 Department of Public Health and Clinical Medicine/Nutritional Research
51 Department of Physiology/Endocrinology
52 Department of Clinical Physiology
53 Steno Diabetes Centre
54 CBMR - Novo Nordisk Foundation Center for Basic Metabolic Research
55 Faculty of Health Sciences
56 Genetic Epidemiology and Clinical Research Group
57 Department of Odontology
58 Department of Medical Statistics
59 LIKES Research Center for Sport and Health Sciences
60 Finnish Institute of Occupational Health
61 Department of Medicine
62 Institute of Public Health and Clinical Nutrition
63 Human Genomics Laboratory
64 Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations
65 Division of Endocrinology, Diabetes and Nutrition
66 Institute of Cell and Molecular Biosciences
67 Centre for Bone and Arthritis Research
68 Geriatric Rehabilitation Unit
69 Netherlands Genomics Initiative
70 Faculty of Epidemiology and Population Health [London]
71 Icelandic Heart Association
72 University of Iceland [Reykjavik]
73 Department of Public Health
74 South Ostrobothnia Central Hospital
75 Department of Clinical and Preventive Medicine
76 Department of Clinical Chemistry
77 Department of Clinical Physiology
78 Folkhälsan Research Centre
79 Department of Pediatrics
80 Center for Human Genetic Research and Diabetes Research Center
81 Department of Medicine
82 Program for Medical and Population Genetics
83 Center for Metabolic Disease Prevention
84 School of Oral and Dental Sciences
85 Department of Medicine
86 Department of Genomics of Common Disease
87 Department of Epidemiology and Public Health
88 Department of Public Health and Primary Care
89 Faculty of Health Sciences
90 Department of Epidemiology
91 Department of Epidemiology and Biostatistics
92 Department of Life Course and Services
Abstract : BACKGROUND: The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute unambiguously whether PA attenuates the association of FTO with obesity risk, we meta-analyzed data from 45 studies of adults (n = 218,166) and nine studies of children and adolescents (n = 19,268). METHODS AND FINDINGS: All studies identified to have data on the FTO rs9939609 variant (or any proxy [r(2)>0.8]) and PA were invited to participate, regardless of ethnicity or age of the participants. PA was standardized by categorizing it into a dichotomous variable (physically inactive versus active) in each study. Overall, 25% of adults and 13% of children were categorized as inactive. Interaction analyses were performed within each study by including the FTO×PA interaction term in an additive model, adjusting for age and sex. Subsequently, random effects meta-analysis was used to pool the interaction terms. In adults, the minor (A-) allele of rs9939609 increased the odds of obesity by 1.23-fold/allele (95% CI 1.20-1.26), but PA attenuated this effect (p(interaction) = 0.001). More specifically, the minor allele of rs9939609 increased the odds of obesity less in the physically active group (odds ratio = 1.22/allele, 95% CI 1.19-1.25) than in the inactive group (odds ratio = 1.30/allele, 95% CI 1.24-1.36). No such interaction was found in children and adolescents. CONCLUSIONS: The association of the FTO risk allele with the odds of obesity is attenuated by 27% in physically active adults, highlighting the importance of PA in particular in those genetically predisposed to obesity.
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Tuomas Kilpeläinen, Lu Qi, Soren Brage, Stephen Sharp, Emily Sonestedt, et al.. Physical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218,166 adults and 19,268 children.. PLoS Medicine, Public Library of Science, 2011, 8 (11), pp.e1001116. ⟨10.1371/journal.pmed.1001116⟩. ⟨inserm-00702827⟩

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