Abstract
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.
| Original language | English |
|---|---|
| Journal | P L o S Medicine (Online) |
| Volume | 8 |
| Issue number | 11 |
| Pages (from-to) | e1001116 |
| ISSN | 1549-1277 |
| DOIs | |
| Publication status | Published - 1 Nov 2011 |
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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. / Oskari Kilpeläinen, Tuomas; 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; Stancáková, 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; Bergmann, Sven; Power, Chris; Khaw, Kay-Tee; Chasman, Daniel; Ridker, Paul; Hansen, Torben; Monda, Keri L; Illig, Thomas; Järvelin, Marjo-Riitta; Wareham, Nicholas J; Hu, Frank B; Groop, Leif C; Orho-Melander, Marju; Ekelund, Ulf; Franks, Paul W; Loos, Ruth J F.
In: P L o S Medicine (Online), Vol. 8, No. 11, 01.11.2011, p. e1001116.Research output: Contribution to journal › Journal article › Research › peer-review
}
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 -