Physical Activity Attenuates the Influence of FTO Variants on Obesity Risk: A Meta-Analysis of 218,166 Adults and 19,268 Children

Title: Physical Activity Attenuates the Influence of FTO Variants on Obesity Risk: A Meta-Analysis of 218,166 Adults and 19,268 Children
Authors: Kilpelaeinen, TO
Qi, L
Brage, S
Sharp, SJ
Sonestedt, E
Demerath, E
Ahmad, T
Mora, S
Kaakinen, M
Sandholt, CH
Holzapfel, C
Autenrieth, CS
Hyppoenen, E
Cauchi, S
He, M
Kutalik, Z
Kumari, M
Stancakova, A
Meidtner, K
Balkau, B
Tan, JT
Mangino, M
Timpson, NJ
Song, Y
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
Martinez Larrad, MT
Atalay, M
Hakanen, M
Amin, N
Cavalcanti-Proenca, C
Grontved, A
Hallmans, G
Jansson, J-O
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
Serrano Rios, M
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, S
Ness, A
Spector, TD
Tai, ES
Froguel, P
Boeing, H
Laakso, M
Marmot, M
Bergmann, S
Power, C
Khaw, K-T
Chasman, D
Ridker, P
Hansen, T
Monda, KL
Illig, T
Jarvelin, M-R
Wareham, NJ
Hu, FB
Groop, LC
Orho-Melander, M
Ekelund, U
Franks, PW
Loos, RJF
Item Type: Journal Article
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 [r2>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 (pinteraction  = 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.
Issue Date: 1-Nov-2011
Date of Acceptance: 23-Sep-2011
ISSN: 1549-1277
Publisher: Public Library of Science
Journal / Book Title: PLOS Medicine
Volume: 8
Issue: 11
Copyright Statement: © 2011 Loos et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Sponsor/Funder: Medical Research Council (MRC)
Funder's Grant Number: G0801056B
Keywords: Science & Technology
Life Sciences & Biomedicine
Medicine, General & Internal
General & Internal Medicine
Adipose Tissue
Alpha-Ketoglutarate-Dependent Dioxygenase FTO
Genetic Predisposition to Disease
Motor Activity
Polymorphism, Single Nucleotide
Risk Factors
11 Medical And Health Sciences
Publication Status: Published
Article Number: ARTN e1001116
Appears in Collections:Department of Medicine
Faculty of Medicine
Epidemiology, Public Health and Primary Care

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