Physical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218,166 adults and 19,268 children.
<h4>Background</h4>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...
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oai:doaj.org-article:24b83ba2531543f5868dde36644488972021-11-18T05:42:28ZPhysical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218,166 adults and 19,268 children.1549-12771549-167610.1371/journal.pmed.1001116https://doaj.org/article/24b83ba2531543f5868dde36644488972011-11-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22069379/pdf/?tool=EBIhttps://doaj.org/toc/1549-1277https://doaj.org/toc/1549-1676<h4>Background</h4>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).<h4>Methods and findings</h4>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.<h4>Conclusions</h4>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.Tuomas O KilpeläinenLu QiSoren BrageStephen J SharpEmily SonestedtEllen DemerathTariq AhmadSamia MoraMarika KaakinenCamilla Helene SandholtChristina HolzapfelChristine S AutenriethElina HyppönenStéphane CauchiMeian HeZoltan KutalikMeena KumariAlena StančákováKarina MeidtnerBeverley BalkauJonathan T TanMassimo ManginoNicholas J TimpsonYiqing SongM Carola ZillikensKathleen A JablonskiMelissa E GarciaStefan JohanssonJennifer L Bragg-GreshamYing WuJana V van Vliet-OstaptchoukN Charlotte Onland-MoretEsther ZimmermannNatalia V RiveraToshiko TanakaHeather M StringhamGünther SilbernagelStavroula KanoniMary F FeitosaSoren SnitkerJonatan R RuizJeffery MetterMaria Teresa Martinez LarradMustafa AtalayMaarit HakanenNajaf AminChristine Cavalcanti-ProençaAnders GrøntvedGöran HallmansJohn-Olov JanssonJohanna KuusistoMika KähönenPamela L LutseyJohn J NolanLuigi PallaOluf PedersenLouis PérusseFrida RenströmRobert A ScottDmitry ShunginUlla SovioTuija H TammelinTapani RönnemaaTimo A LakkaMatti UusitupaManuel Serrano RiosLuigi FerrucciClaude BouchardAline MeirhaegheMao FuMark WalkerIngrid B BoreckiGeorge V DedoussisAndreas FritscheClaes OhlssonMichael BoehnkeStefania BandinelliCornelia M van DuijnShah EbrahimDebbie A LawlorVilmundur GudnasonTamara B HarrisThorkild I A SørensenKaren L MohlkeAlbert HofmanAndré G UitterlindenJaakko TuomilehtoTerho LehtimäkiOlli RaitakariBo IsomaaPål R NjølstadJose C FlorezSimin LiuAndy NessTimothy D SpectorE Shyong TaiPhilippe FroguelHeiner BoeingMarkku LaaksoMichael MarmotSven BergmannChris PowerKay-Tee KhawDaniel ChasmanPaul RidkerTorben HansenKeri L MondaThomas IlligMarjo-Riitta JärvelinNicholas J WarehamFrank B HuLeif C GroopMarju Orho-MelanderUlf EkelundPaul W FranksRuth J F LoosPublic Library of Science (PLoS)articleMedicineRENPLoS Medicine, Vol 8, Iss 11, p e1001116 (2011) |
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DOAJ |
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Medicine R |
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Medicine R Tuomas O Kilpeläinen Lu Qi Soren Brage Stephen J Sharp Emily Sonestedt Ellen Demerath Tariq Ahmad Samia Mora Marika Kaakinen Camilla Helene Sandholt Christina Holzapfel Christine S Autenrieth Elina Hyppönen Stéphane Cauchi Meian He Zoltan Kutalik Meena Kumari Alena Stančáková Karina Meidtner Beverley Balkau Jonathan T Tan Massimo Mangino Nicholas J Timpson Yiqing Song M Carola Zillikens Kathleen A Jablonski Melissa E Garcia Stefan Johansson Jennifer L Bragg-Gresham Ying Wu Jana V van Vliet-Ostaptchouk N Charlotte Onland-Moret Esther Zimmermann Natalia V Rivera Toshiko Tanaka Heather M Stringham Günther Silbernagel Stavroula Kanoni Mary F Feitosa Soren Snitker Jonatan R Ruiz Jeffery Metter Maria Teresa Martinez Larrad Mustafa Atalay Maarit Hakanen Najaf Amin Christine Cavalcanti-Proença Anders Grøntved Göran Hallmans John-Olov Jansson Johanna Kuusisto Mika Kähönen Pamela L Lutsey John J Nolan Luigi Palla Oluf Pedersen Louis Pérusse Frida Renström Robert A Scott Dmitry Shungin Ulla Sovio Tuija H Tammelin Tapani Rönnemaa Timo A Lakka Matti Uusitupa Manuel Serrano Rios Luigi Ferrucci Claude Bouchard Aline Meirhaeghe Mao Fu Mark Walker Ingrid B Borecki George V Dedoussis Andreas Fritsche Claes Ohlsson Michael Boehnke Stefania Bandinelli Cornelia M van Duijn Shah Ebrahim Debbie A Lawlor Vilmundur Gudnason Tamara B Harris Thorkild I A Sørensen Karen L Mohlke Albert Hofman André G Uitterlinden Jaakko Tuomilehto Terho Lehtimäki Olli Raitakari Bo Isomaa Pål R Njølstad Jose C Florez Simin Liu Andy Ness Timothy D Spector E Shyong Tai Philippe Froguel Heiner Boeing Markku Laakso Michael Marmot Sven Bergmann Chris Power Kay-Tee Khaw Daniel Chasman Paul Ridker Torben Hansen Keri L Monda Thomas Illig Marjo-Riitta Järvelin Nicholas J Wareham Frank B Hu Leif C Groop Marju Orho-Melander Ulf Ekelund Paul W Franks Ruth J F Loos Physical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218,166 adults and 19,268 children. |
| description |
<h4>Background</h4>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).<h4>Methods and findings</h4>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.<h4>Conclusions</h4>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. |
| format |
article |
| author |
Tuomas O Kilpeläinen Lu Qi Soren Brage Stephen J Sharp Emily Sonestedt Ellen Demerath Tariq Ahmad Samia Mora Marika Kaakinen Camilla Helene Sandholt Christina Holzapfel Christine S Autenrieth Elina Hyppönen Stéphane Cauchi Meian He Zoltan Kutalik Meena Kumari Alena Stančáková Karina Meidtner Beverley Balkau Jonathan T Tan Massimo Mangino Nicholas J Timpson Yiqing Song M Carola Zillikens Kathleen A Jablonski Melissa E Garcia Stefan Johansson Jennifer L Bragg-Gresham Ying Wu Jana V van Vliet-Ostaptchouk N Charlotte Onland-Moret Esther Zimmermann Natalia V Rivera Toshiko Tanaka Heather M Stringham Günther Silbernagel Stavroula Kanoni Mary F Feitosa Soren Snitker Jonatan R Ruiz Jeffery Metter Maria Teresa Martinez Larrad Mustafa Atalay Maarit Hakanen Najaf Amin Christine Cavalcanti-Proença Anders Grøntved Göran Hallmans John-Olov Jansson Johanna Kuusisto Mika Kähönen Pamela L Lutsey John J Nolan Luigi Palla Oluf Pedersen Louis Pérusse Frida Renström Robert A Scott Dmitry Shungin Ulla Sovio Tuija H Tammelin Tapani Rönnemaa Timo A Lakka Matti Uusitupa Manuel Serrano Rios Luigi Ferrucci Claude Bouchard Aline Meirhaeghe Mao Fu Mark Walker Ingrid B Borecki George V Dedoussis Andreas Fritsche Claes Ohlsson Michael Boehnke Stefania Bandinelli Cornelia M van Duijn Shah Ebrahim Debbie A Lawlor Vilmundur Gudnason Tamara B Harris Thorkild I A Sørensen Karen L Mohlke Albert Hofman André G Uitterlinden Jaakko Tuomilehto Terho Lehtimäki Olli Raitakari Bo Isomaa Pål R Njølstad Jose C Florez Simin Liu Andy Ness Timothy D Spector E Shyong Tai Philippe Froguel Heiner Boeing Markku Laakso Michael Marmot Sven Bergmann Chris Power Kay-Tee Khaw Daniel Chasman Paul Ridker Torben Hansen Keri L Monda Thomas Illig Marjo-Riitta Järvelin Nicholas J Wareham Frank B Hu Leif C Groop Marju Orho-Melander Ulf Ekelund Paul W Franks Ruth J F Loos |
| author_facet |
Tuomas O Kilpeläinen Lu Qi Soren Brage Stephen J Sharp Emily Sonestedt Ellen Demerath Tariq Ahmad Samia Mora Marika Kaakinen Camilla Helene Sandholt Christina Holzapfel Christine S Autenrieth Elina Hyppönen Stéphane Cauchi Meian He Zoltan Kutalik Meena Kumari Alena Stančáková Karina Meidtner Beverley Balkau Jonathan T Tan Massimo Mangino Nicholas J Timpson Yiqing Song M Carola Zillikens Kathleen A Jablonski Melissa E Garcia Stefan Johansson Jennifer L Bragg-Gresham Ying Wu Jana V van Vliet-Ostaptchouk N Charlotte Onland-Moret Esther Zimmermann Natalia V Rivera Toshiko Tanaka Heather M Stringham Günther Silbernagel Stavroula Kanoni Mary F Feitosa Soren Snitker Jonatan R Ruiz Jeffery Metter Maria Teresa Martinez Larrad Mustafa Atalay Maarit Hakanen Najaf Amin Christine Cavalcanti-Proença Anders Grøntved Göran Hallmans John-Olov Jansson Johanna Kuusisto Mika Kähönen Pamela L Lutsey John J Nolan Luigi Palla Oluf Pedersen Louis Pérusse Frida Renström Robert A Scott Dmitry Shungin Ulla Sovio Tuija H Tammelin Tapani Rönnemaa Timo A Lakka Matti Uusitupa Manuel Serrano Rios Luigi Ferrucci Claude Bouchard Aline Meirhaeghe Mao Fu Mark Walker Ingrid B Borecki George V Dedoussis Andreas Fritsche Claes Ohlsson Michael Boehnke Stefania Bandinelli Cornelia M van Duijn Shah Ebrahim Debbie A Lawlor Vilmundur Gudnason Tamara B Harris Thorkild I A Sørensen Karen L Mohlke Albert Hofman André G Uitterlinden Jaakko Tuomilehto Terho Lehtimäki Olli Raitakari Bo Isomaa Pål R Njølstad Jose C Florez Simin Liu Andy Ness Timothy D Spector E Shyong Tai Philippe Froguel Heiner Boeing Markku Laakso Michael Marmot Sven Bergmann Chris Power Kay-Tee Khaw Daniel Chasman Paul Ridker Torben Hansen Keri L Monda Thomas Illig Marjo-Riitta Järvelin Nicholas J Wareham Frank B Hu Leif C Groop Marju Orho-Melander Ulf Ekelund Paul W Franks Ruth J F Loos |
| author_sort |
Tuomas O Kilpeläinen |
| title |
Physical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218,166 adults and 19,268 children. |
| title_short |
Physical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218,166 adults and 19,268 children. |
| title_full |
Physical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218,166 adults and 19,268 children. |
| title_fullStr |
Physical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218,166 adults and 19,268 children. |
| title_full_unstemmed |
Physical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218,166 adults and 19,268 children. |
| title_sort |
physical activity attenuates the influence of fto variants on obesity risk: a meta-analysis of 218,166 adults and 19,268 children. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2011 |
| url |
https://doaj.org/article/24b83ba2531543f5868dde3664448897 |
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physicalactivityattenuatestheinfluenceofftovariantsonobesityriskametaanalysisof218166adultsand19268children AT marjoriittajarvelin physicalactivityattenuatestheinfluenceofftovariantsonobesityriskametaanalysisof218166adultsand19268children AT nicholasjwareham physicalactivityattenuatestheinfluenceofftovariantsonobesityriskametaanalysisof218166adultsand19268children AT frankbhu physicalactivityattenuatestheinfluenceofftovariantsonobesityriskametaanalysisof218166adultsand19268children AT leifcgroop physicalactivityattenuatestheinfluenceofftovariantsonobesityriskametaanalysisof218166adultsand19268children AT marjuorhomelander physicalactivityattenuatestheinfluenceofftovariantsonobesityriskametaanalysisof218166adultsand19268children AT ulfekelund physicalactivityattenuatestheinfluenceofftovariantsonobesityriskametaanalysisof218166adultsand19268children AT paulwfranks physicalactivityattenuatestheinfluenceofftovariantsonobesityriskametaanalysisof218166adultsand19268children AT ruthjfloos physicalactivityattenuatestheinfluenceofftovariantsonobesityriskametaanalysisof218166adultsand19268children |
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