Physical Activity Attenuates the Influence of FTO Variants on Obesity Risk: A Meta-Analysis of 218,166 Adults and 19,268 Children
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Author
Kilpeläinen, Tuomas O.
Qi, Lu
Brage, Soren
Sharp, Stephen J.
Sonestedt, Emily
Demerath, Ellen
Ahmad, Tariq
Mora, Samia
Kaakinen, Marika
Sandholt, Camilla Helene
Holzapfel, Christina
Autenrieth, Christine S.
Hyppönen, Elina
Cauchi, Stéphane
He, Meian
Kutalik, Zoltan
Kumari, Meena
Stančáková, Alena
Meidtner, Karina
Balkau, Beverley
Tan, Jonathan T.
Mangino, Massimo
Timpson, Nicholas J.
Song, Yiqing
Zillikens, M. Carola
Jablonski, Kathleen A.
Garcia, Melissa E.
Johansson, Stefan
Bragg-Gresham, Jennifer L.
Wu, Ying
van Vliet-Ostaptchouk, Jana V.
Onland-Moret, N. Charlotte
Zimmermann, Esther
Rivera, Natalia V.
Tanaka, Toshiko
Stringham, Heather M.
Silbernagel, Günther
Kanoni, Stavroula
Feitosa, Mary F.
Snitker, Soren
Ruiz, Jonatan R.
Metter, Jeffery
Larrad, Maria Teresa Martinez
Atalay, Mustafa
Hakanen, Maarit
Amin, Najaf
Cavalcanti-Proença, Christine
Grøntved, Anders
Hallmans, Göran
Jansson, John-Olov
Kuusisto, Johanna
Kähönen, Mika
Lutsey, Pamela L.
Nolan, John J.
Palla, Luigi
Pedersen, Oluf
Pérusse, Louis
Renström, Frida
Scott, Robert A.
Shungin, Dmitry
Sovio, Ulla
Tammelin, Tuija H.
Rönnemaa, Tapani
Lakka, Timo A.
Uusitupa, Matti
Rios, Manuel Serrano
Ferrucci, Luigi
Bouchard, Claude
Meirhaeghe, Aline
Fu, Mao
Walker, Mark
Borecki, Ingrid B.
Dedoussis, George V.
Fritsche, Andreas
Ohlsson, Claes
Boehnke, Michael
Bandinelli, Stefania
van Duijn, Cornelia M.
Ebrahim, Shah
Lawlor, Debbie A.
Gudnason, Vilmundur
Harris, Tamara B.
Sørensen, Thorkild I. A.
Mohlke, Karen L.
Hofman, Albert
Uitterlinden, André G.
Tuomilehto, Jaakko
Lehtimäki, Terho
Raitakari, Olli
Isomaa, Bo
Njølstad, Pål R.
Florez, Jose C.
Liu, Simin
Ness, Andy
Spector, Timothy D.
Tai, E. Shyong
Froguel, Philippe
Boeing, Heiner
Laakso, Markku
Marmot, Michael
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https://doi.org/10.1371/journal.pmed.1001116Metadata
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Kilpeläinen, Tuomas O., Lu Qi, Soren Brage, Stephen J. Sharp, Emily Sonestedt, Ellen Demerath, Tariq Ahmad, et al. 2011. “Physical Activity Attenuates the Influence of FTO Variants on Obesity Risk: A Meta-Analysis of 218,166 Adults and 19,268 Children.” Edited by Cathryn Lewis. PLoS Medicine 8 (11): e1001116. https://doi.org/10.1371/journal.pmed.1001116.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 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.Terms of Use
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