Physical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218,166 adults and 19,268 children

Publication

Physical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218,166 adults and 19,268 children

Journal Paper/Review - Nov 1, 2011

Scott Robert A, 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, Fritsche Andreas, Dedoussis George V, Borecki Ingrid B, 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, Tuomilehto Jaakko, Lehtimäki Terho, Chasman Daniel, Ridker Paul, Hansen Torben, Monda Keri L, Illig Thomas, Jarvelin Marjo-Riitta, Wareham Nicholas J, Hu Frank B, Groop Leif C, Orho-Melander Marju, Ekelund Ulf, Franks Paul W, Khaw Kay-Tee, Power Chris, Bergmann Sven, 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, Loos Ruth J F, Kilpeläinen Tuomas O, 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, Kutalik Zoltán, He Meian, Cauchi Stéphane, 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, Bragg-Gresham Jennifer L, Wu Ying, 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, Hakanen Maarit, Atalay Mustafa, Larrad Maria Teresa Martinez, 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, Renström Frida

Citation

Scott R, Ohlsson C, Boehnke M, Bandinelli S, van Duijn C, Ebrahim S, Lawlor D, Gudnason V, Harris T, Sørensen T, Mohlke K, Hofman A, Uitterlinden A, Fritsche A, Dedoussis G, Borecki I, Shungin D, Sovio U, Tammelin T, Rönnemaa T, Lakka T, Uusitupa M, Rios M, Ferrucci L, Bouchard C, Meirhaeghe A, Fu M, Walker M, Tuomilehto J, Lehtimäki T, Chasman D, Ridker P, Hansen T, Monda K, Illig T, Jarvelin M, Wareham N, Hu F, Groop L, Orho-Melander M, Ekelund U, Franks P, Khaw K, Power C, Bergmann S, Raitakari O, Isomaa B, Njølstad P, Florez J, Liu S, Ness A, Spector T, Tai E, Froguel P, Boeing H, Laakso M, Marmot M, Loos R, Kilpeläinen T, Kumari M, Stančáková A, Meidtner K, Balkau B, Tan J, Mangino M, Timpson N, Song Y, Zillikens M, Jablonski K, Garcia M, Johansson S, Kutalik Z, He M, Cauchi S, Qi L, Brage S, Sharp S, Sonestedt E, Demerath E, Ahmad T, Mora S, Kaakinen M, Sandholt C, Holzapfel C, Autenrieth C, Hyppönen E, Bragg-Gresham J, Wu Y, Amin N, Cavalcanti-Proença C, Grøntved A, Hallmans G, Jansson J, Kuusisto J, Kähönen M, Lutsey P, Nolan J, Palla L, Pedersen O, Pérusse L, Hakanen M, Atalay M, Larrad M, van Vliet-Ostaptchouk J, Onland-Moret N, Zimmermann E, Rivera N, Tanaka T, Stringham H, Silbernagel G, Kanoni S, Feitosa M, Snitker S, Ruiz J, Metter J, Renström F. Physical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218,166 adults and 19,268 children. PLoS Med 2011; 8:e1001116.

Type

Journal Paper/Review (English)

Journal

PLoS Med 2011; 8

Publication Date

Nov 1, 2011

Issn Electronic

1549-1676

Pages

e1001116

Brief description/objective

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 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.

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.