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Lookup NU author(s): Professor Mark Walker
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 FTOxPA 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.
Author(s): Kilpelainen TO, Qi L, Brage S, Sharp SJ, Sonestedt E, Demerath E, Ahmad T, Mora S, Kaakinen M, Sandholt CH, Holzapfel C, Autenrieth CS, Hypponen E, Cauchi S, He MA, Kutalik Z, Kumari M, Stancakova A, Meidtner K, Balkau B, Tan JT, Mangino M, Timpson NJ, Song YQ, Zillikens MC, Jablonski KA, Garcia ME, Johansson S, Bragg-Gresham JL, Wu Y, van Vliet-Ostaptchouk JV, Onland-Moret NC, Zimmermann E, Rivera NV, Tanaka T, Stringham HM, Silbernagel G, Kanoni S, Feitosa MF, Snitker S, Ruiz JR, Metter J, Larrad MTM, Atalay M, Hakanen M, Amin N, Cavalcanti-Proenca C, Grontved A, Hallmans G, Jansson JO, Kuusisto J, Kahonen M, Lutsey PL, Nolan JJ, Palla L, Pedersen O, Perusse L, Renstrom F, Scott RA, Shungin D, Sovio U, Tammelin TH, Ronnemaa T, Lakka TA, Uusitupa M, Rios MS, Ferrucci L, Bouchard C, Meirhaeghe A, Fu M, Walker M, Borecki IB, Dedoussis GV, Fritsche A, Ohlsson C, Boehnke M, Bandinelli S, van Duijn CM, Ebrahim S, Lawlor DA, Gudnason V, Harris TB, Sorensen TIA, Mohlke KL, Hofman A, Uitterlinden AG, Tuomilehto J, Lehtimaki T, Raitakari O, Isomaa B, Njolstad PR, Florez JC, Liu SM, Ness A, Spector TD, Tai ES, Froguel P, Boeing H, Laakso M, Marmot M, Bergmann S, Power C, Khaw KT, Chasman D, Ridker P, Hansen T, Monda KL, Illig T, Jarvelin MR, Wareham NJ, Hu FB, Groop LC, Orho-Melander M, Ekelund U, Franks PW, Loos RJF
Publication type: Article
Publication status: Published
Journal: PLoS Medicine
Year: 2011
Volume: 8
Issue: 11
Print publication date: 01/11/2011
Date deposited: 01/03/2012
ISSN (electronic): 1549-1277
Publisher: Public Library of Science
URL: http://dx.doi.org/10.1371/journal.pmed.1001116
DOI: 10.1371/journal.pmed.1001116
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