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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

Kilpelaeinen, Tuomas O.; Qi, Lu; Brage, Soren; Sharp, Stephen J.; Sonestedt, Emily LU ; Demerath, Ellen; Ahmad, Tariq; Mora, Samia; Kaakinen, Marika and Sandholt, Camilla Helene, et al. (2011) In PLoS Medicine 8(11).
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... (More)
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. (Less)
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PLoS Medicine
volume
8
issue
11
publisher
Public Library of Science
external identifiers
  • wos:000298133100003
  • scopus:82455175773
ISSN
1549-1676
DOI
10.1371/journal.pmed.1001116
language
English
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yes
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c38f2e29-1e58-4f8a-958b-3444b1ecb511 (old id 2348174)
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2012-03-01 11:26:07
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2017-10-22 03:29:10
@article{c38f2e29-1e58-4f8a-958b-3444b1ecb511,
  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.},
  author       = {Kilpelaeinen, Tuomas O. and Qi, Lu and Brage, Soren and Sharp, Stephen J. and Sonestedt, Emily and Demerath, Ellen and Ahmad, Tariq and Mora, Samia and Kaakinen, Marika and Sandholt, Camilla Helene and Holzapfel, Christina and Autenrieth, Christine S. and Hyppoenen, Elina and Cauchi, Stephane and He, Meian and Kutalik, Zoltan and Kumari, Meena and Stancakova, Alena and Meidtner, Karina and Balkau, Beverley and Tan, Jonathan T. and Mangino, Massimo and Timpson, Nicholas J. and Song, Yiqing and Zillikens, M. Carola and Jablonski, Kathleen A. and Garcia, Melissa E. and Johansson, Stefan and Bragg-Gresham, Jennifer L. and Wu, Ying and van Vliet-Ostaptchouk, Jana V. and Onland-Moret, N. Charlotte and Zimmermann, Esther and Rivera, Natalia V. and Tanaka, Toshiko and Stringham, Heather M. and Silbernagel, Guenther and Kanoni, Stavroula and Feitosa, Mary F. and Snitker, Soren and Ruiz, Jonatan R. and Metter, Jeffery and Martinez Larrad, Maria Teresa and Atalay, Mustafa and Hakanen, Maarit and Amin, Najaf and Cavalcanti-Proenca, Christine and Grontved, Anders and Hallmans, Goran and Jansson, John-Olov and Kuusisto, Johanna and Kahonen, Mika and Lutsey, Pamela L. and Nolan, John J. and Palla, Luigi and Pedersen, Oluf and Perusse, Louis and Renstrom, Frida and Scott, Robert A. and Shungin, Dmitry and Sovio, Ulla and Tammelin, Tuija H. and Ronnemaa, Tapani and Lakka, Timo A. and Uusitupa, Matti and Serrano Rios, Manuel and Ferrucci, Luigi and Bouchard, Claude and Meirhaeghe, Aline and Fu, Mao and Walker, Mark and Borecki, Ingrid B. and Dedoussis, George V. and Fritsche, Andreas and Ohlsson, Claes and Boehnke, Michael and Bandinelli, Stefania and van Duijn, Cornelia M. and Ebrahim, Shah and Lawlor, Debbie A. and Gudnason, Vilmundur and Harris, Tamara B. and Sorensen, Thorkild I. A. and Mohlke, Karen L. and Hofman, Albert and Uitterlinden, Andre G. and Tuomilehto, Jaakko and Lehtimaki, Terho and Raitakari, Olli and Isomaa, Bo and Njolstad, Pal R. and Florez, Jose C. and Liu, Simin and Ness, Andy and Spector, Timothy D. and Tai, E. Shyong and Froguel, Philippe and Boeing, Heiner and Laakso, Markku and Marmot, Michael and Bergmann, Sven and Power, Chris and Khaw, Kay-Tee and Chasman, Daniel and Ridker, Paul and Hansen, Torben and Monda, Keri L. and Illig, Thomas and Jarvelin, Marjo-Riitta and Wareham, Nicholas J. and Hu, Frank B. and Groop, Leif and Orho-Melander, Marju and Ekelund, Ulf and Franks, Paul and Loos, Ruth J. F.},
  issn         = {1549-1676},
  language     = {eng},
  number       = {11},
  publisher    = {Public Library of Science},
  series       = {PLoS Medicine},
  title        = {Physical Activity Attenuates the Influence of FTO Variants on Obesity Risk: A Meta-Analysis of 218,166 Adults and 19,268 Children},
  url          = {http://dx.doi.org/10.1371/journal.pmed.1001116},
  volume       = {8},
  year         = {2011},
}