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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.

Authors :
Kilpeläinen TO
Qi L
Brage S
Sharp SJ
Sonestedt E
Demerath E
Ahmad T
Mora S
Kaakinen M
Sandholt CH
Holzapfel C
Autenrieth CS
Hyppönen E
Cauchi S
He M
Kutalik Z
Kumari M
Stančáková 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
Larrad MT
Atalay M
Hakanen M
Amin N
Cavalcanti-Proença C
Grøntved A
Hallmans G
Jansson JO
Kuusisto J
Kähönen M
Lutsey PL
Nolan JJ
Palla L
Pedersen O
Pérusse L
Renström F
Scott RA
Shungin D
Sovio U
Tammelin TH
Rönnemaa 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
Sørensen TI
Mohlke KL
Hofman A
Uitterlinden AG
Tuomilehto J
Lehtimäki T
Raitakari O
Isomaa B
Njølstad PR
Florez JC
Liu S
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
Järvelin MR
Wareham NJ
Hu FB
Groop LC
Orho-Melander M
Ekelund U
Franks PW
Loos RJ
Source :
PLoS medicine [PLoS Med] 2011 Nov; Vol. 8 (11), pp. e1001116. Date of Electronic Publication: 2011 Nov 01.
Publication Year :
2011

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).<br />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.<br />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.

Details

Language :
English
ISSN :
1549-1676
Volume :
8
Issue :
11
Database :
MEDLINE
Journal :
PLoS medicine
Publication Type :
Academic Journal
Accession number :
22069379
Full Text :
https://doi.org/10.1371/journal.pmed.1001116