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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
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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