TY - JOUR

T1 - Physical Activity Attenuates the Influence of FTO Variants on Obesity Risk

T2 - A Meta-Analysis of 218,166 Adults and 19,268 Children

AU - Oskari Kilpeläinen, Tuomas

AU - Qi, Lu

AU - Brage, Soren

AU - Sharp, Stephen J

AU - Sonestedt, Emily

AU - Demerath, Ellen

AU - Ahmad, Tariq

AU - Mora, Samia

AU - Kaakinen, Marika

AU - Sandholt, Camilla Helene

AU - Holzapfel, Christina

AU - Autenrieth, Christine S

AU - Hyppönen, Elina

AU - Cauchi, Stéphane

AU - He, Meian

AU - Kutalik, Zoltan

AU - Kumari, Meena

AU - Stancáková, Alena

AU - Meidtner, Karina

AU - Balkau, Beverley

AU - Tan, Jonathan T

AU - Mangino, Massimo

AU - Timpson, Nicholas J

AU - Song, Yiqing

AU - Zillikens, M Carola

AU - Jablonski, Kathleen A

AU - Garcia, Melissa E

AU - Johansson, Stefan

AU - Bragg-Gresham, Jennifer L

AU - Wu, Ying

AU - van Vliet-Ostaptchouk, Jana V

AU - Onland-Moret, N Charlotte

AU - Zimmermann, Esther

AU - Rivera, Natalia V

AU - Tanaka, Toshiko

AU - Stringham, Heather M

AU - Silbernagel, Günther

AU - Kanoni, Stavroula

AU - Feitosa, Mary F

AU - Snitker, Soren

AU - Ruiz, Jonatan R

AU - Metter, Jeffery

AU - Larrad, Maria Teresa Martinez

AU - Atalay, Mustafa

AU - Hakanen, Maarit

AU - Amin, Najaf

AU - Cavalcanti-Proença, Christine

AU - Grøntved, Anders

AU - Hallmans, Göran

AU - Jansson, John-Olov

AU - Kuusisto, Johanna

AU - Kähönen, Mika

AU - Lutsey, Pamela L

AU - Nolan, John J

AU - Palla, Luigi

AU - Pedersen, Oluf

AU - Pérusse, Louis

AU - Renström, Frida

AU - Scott, Robert A

AU - Shungin, Dmitry

AU - Sovio, Ulla

AU - Tammelin, Tuija H

AU - Rönnemaa, Tapani

AU - Lakka, Timo A

AU - Uusitupa, Matti

AU - Rios, Manuel Serrano

AU - Ferrucci, Luigi

AU - Bouchard, Claude

AU - Meirhaeghe, Aline

AU - Fu, Mao

AU - Walker, Mark

AU - Borecki, Ingrid B

AU - Dedoussis, George V

AU - Fritsche, Andreas

AU - Ohlsson, Claes

AU - Boehnke, Michael

AU - Bandinelli, Stefania

AU - van Duijn, Cornelia M

AU - Ebrahim, Shah

AU - Lawlor, Debbie A

AU - Gudnason, Vilmundur

AU - Harris, Tamara B

AU - Sørensen, Thorkild I A

AU - Mohlke, Karen L

AU - Hofman, Albert

AU - Uitterlinden, André G

AU - Tuomilehto, Jaakko

AU - Lehtimäki, Terho

AU - Raitakari, Olli

AU - Isomaa, Bo

AU - Njølstad, Pål R

AU - Florez, Jose C

AU - Liu, Simin

AU - Ness, Andy

AU - Spector, Timothy D

AU - Tai, E Shyong

AU - Froguel, Philippe

AU - Boeing, Heiner

AU - Laakso, Markku

AU - Marmot, Michael

AU - Bergmann, Sven

AU - Power, Chris

AU - Khaw, Kay-Tee

AU - Chasman, Daniel

AU - Ridker, Paul

AU - Hansen, Torben

AU - Monda, Keri L

AU - Illig, Thomas

AU - Järvelin, Marjo-Riitta

AU - Wareham, Nicholas J

AU - Hu, Frank B

AU - Groop, Leif C

AU - Orho-Melander, Marju

AU - Ekelund, Ulf

AU - Franks, Paul W

AU - Loos, Ruth J F

PY - 2011/11/1

Y1 - 2011/11/1

N2 - BackgroundThe 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 FindingsAll 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.ConclusionsThe 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.

AB - BackgroundThe 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 FindingsAll 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.ConclusionsThe 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.

U2 - 10.1371/journal.pmed.1001116

DO - 10.1371/journal.pmed.1001116

M3 - Journal article

C2 - 22069379

VL - 8

SP - e1001116

JO - P L o S Medicine (Online)

JF - P L o S Medicine (Online)

SN - 1549-1277

IS - 11

ER -