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

Tuomas Kilpeläinen; Lu Qi; Soren Brage; Stephen Sharp; Emily Sonestedt; Ellen Demerath; Tariq Ahmad; Samia Mora; Marika Kaakinen; Camilla Helene Sandholt; Christina Holzapfel; Christine Autenrieth; Elina Hyppönen; Stéphane Cauchi; Meian He; Zoltan Kutalik; Meena Kumari; Alena Stančáková; Karina Meidtner; Beverley Balkau; Jonathan Tan; Massimo Mangino; Nicholas Timpson; Yiqing Song; M Carola Zillikens; Kathleen Jablonski; Melissa Garcia; Stefan Johansson; Jennifer Bragg-Gresham; Ying Wu; Jana van Vliet-Ostaptchouk; N Charlotte Onland-Moret; Esther Zimmermann; Natalia Rivera; Toshiko Tanaka; Heather Stringham; Günther Silbernagel; Stavroula Kanoni; Mary Feitosa; Soren Snitker; Jonatan 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 Lutsey; John Nolan; Luigi Palla; Oluf Pedersen; Louis Pérusse; Frida Renström; Robert Scott; Dmitry Shungin; Ulla Sovio; Tuija Tammelin; Tapani Rönnemaa; Timo Lakka; Matti Uusitupa; Manuel Serrano Rios; Luigi Ferrucci; Claude Bouchard; Aline Meirhaeghe; Mao Fu; Mark Walker; Ingrid Borecki; George Dedoussis; Andreas Fritsche; Claes Ohlsson; Michael Boehnke; Stefania Bandinelli; Cornelia van Duijn; Shah Ebrahim; Debbie Lawlor; Vilmundur Gudnason; Tamara Harris; Thorkild Sørensen; Karen Mohlke; Albert Hofman; André Uitterlinden; Jaakko Tuomilehto; Terho Lehtimäki; Olli Raitakari; Bo Isomaa; Pål Njølstad; Jose Florez; Simin Liu; Andy Ness; Timothy Spector; E Shyong Tai; Philippe Froguel; Heiner Boeing; Markku Laakso; Michael Marmot; Göteborgs universitet

doi:10.1371/journal.pmed.1001116

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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

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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

Tuomas Kilpeläinen, Lu Qi, Soren Brage, Stephen Sharp, Emily Sonestedt, Ellen Demerath, Tariq Ahmad, Samia Mora, Marika Kaakinen, Camilla Helene Sandholt, …

PLoS medicine, Vol.8(11), pp.e1001116-e1001116

01/11/2011

DOI: https://doi.org/10.1371/journal.pmed.1001116

PMID: 22069379

Abstract

Adipose Tissue

Adolescent

Adult

Aged

Child

Female

Genetic Predisposition to Disease

Genotype

Humans

Life Sciences

Male

Motor Activity

Obesity

Polymorphism, Single Nucleotide

Proteins

Risk Factors

Santé publique et épidémiologie

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.

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Title: Physical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218,166 adults and 19,268 children
Creators - without role: Tuomas Kilpeläinen - Medical Research Council
Lu Qi - Harvard University
Soren Brage - Medical Research Council
Stephen Sharp - Medical Research Council
Emily Sonestedt - Lund University
Ellen Demerath - University of Minnesota
Tariq Ahmad - Duke Medical Center
Samia Mora - Brigham and Women's Hospital
Marika Kaakinen - University of Oulu
Camilla Helene Sandholt - Hagedorn Research Institute
Christina Holzapfel - Helmholtz Zentrum München
Christine Autenrieth - Helmholtz Zentrum München
Elina Hyppönen - UCL Australia
Stéphane Cauchi - Institut de Biologie de Lille
Meian He - Harvard School of Public Health
Zoltan Kutalik - University of Lausanne
Meena Kumari - University College London
Alena Stančáková - University of Eastern Finland
Karina Meidtner - German Institute of Human Nutrition
Beverley Balkau - University of Paris-Sud
Jonathan Tan - National University of Singapore
Massimo Mangino - King's College London
Nicholas Timpson - University of Bristol
Yiqing Song - Brigham and Women's Hospital
M Carola Zillikens - Erasmus MC
Kathleen Jablonski - George Washington University
Melissa Garcia - National Institute on Aging
Stefan Johansson - Haukeland University Hospital
Jennifer Bragg-Gresham - University of Michigan–Ann Arbor
Ying Wu - University of North Carolina at Chapel Hill
Jana van Vliet-Ostaptchouk - University Medical Center Groningen
N Charlotte Onland-Moret - University Medical Center Utrecht
Esther Zimmermann - Copenhagen University Hospital
Natalia Rivera - Erasmus University Rotterdam
Toshiko Tanaka - National Institutes of Health
Heather Stringham - University of Michigan–Ann Arbor
Günther Silbernagel - University of Tübingen
Stavroula Kanoni - Harokopio University of Athens
Mary Feitosa - Washington University in St. Louis
Soren Snitker - University of Maryland, College Park
Jonatan Ruiz - Karolinska Institutet
Jeffery Metter - National Institute on Aging
Maria Teresa Martinez Larrad - Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas
Mustafa Atalay - University of Eastern Finland
Maarit Hakanen - University of Turku
Najaf Amin - Erasmus MC
Christine Cavalcanti-Proença - Institut de Biologie de Lille
Anders Grøntved - University of Southern Denmark
Göran Hallmans - Umeå University
John-Olov Jansson - University of Gothenburg
Johanna Kuusisto - Kuopio University Hospital
Mika Kähönen - Tampere University Hospital
Pamela Lutsey - University of Minnesota
John Nolan - Steno Diabetes Center
Luigi Palla - Medical Research Council
Oluf Pedersen - University of Copenhagen
Louis Pérusse - Université Laval
Frida Renström - Skåne University Hospital
Robert Scott - Medical Research Council
Dmitry Shungin - Lund University
Ulla Sovio - London School of Hygiene & Tropical Medicine
Tuija Tammelin - Finnish Institute of Occupational Health
Tapani Rönnemaa - University of Turku
Timo Lakka - University of Eastern Finland
Matti Uusitupa - University of Eastern Finland
Manuel Serrano Rios - Hospital Clínico San Carlos
Luigi Ferrucci - National Institute on Aging
Claude Bouchard - Pennington Biomedical Research Center
Aline Meirhaeghe - University of Lille Nord de France
Mao Fu - University of Maryland, Baltimore
Mark Walker - University of Newcastle Australia
Ingrid Borecki - Washington University in St. Louis
George Dedoussis - Harokopio University of Athens
Andreas Fritsche - University of Tübingen
Claes Ohlsson - University of Gothenburg
Michael Boehnke - University of Michigan–Ann Arbor
Stefania Bandinelli - Azienda Sanitaria di Firenze
Cornelia van Duijn - Erasmus University Rotterdam
Shah Ebrahim - London School of Hygiene & Tropical Medicine
Debbie Lawlor - University of Bristol
Vilmundur Gudnason - Icelandic Heart Association
Tamara Harris - National Institute on Aging
Thorkild Sørensen - Institute of Preventive Medicine
Karen Mohlke - University of North Carolina at Chapel Hill
Albert Hofman - Erasmus MC
André Uitterlinden - Netherlands Consortium for Healthy Ageing
Jaakko Tuomilehto - Universität für Weiterbildung Krems
Terho Lehtimäki - Tampere University Hospital
Olli Raitakari - Turku University Hospital
Bo Isomaa - Folkhälsans Forskningscentrum
Pål Njølstad - Haukeland University Hospital
Jose Florez - Harvard University
Simin Liu - University of California, Los Angeles
Andy Ness - School of Oral and Dental Sciences
Timothy Spector - King‘s College London
E Shyong Tai - National University of Singapore
Philippe Froguel - Hammersmith Hospital
Heiner Boeing - German Institute of Human Nutrition
Markku Laakso - Kuopio University Hospital
Michael Marmot - University College London
Göteborgs universitet
Publication Details: PLoS medicine, Vol.8(11), pp.e1001116-e1001116
Publisher: Public Library of Science
Identifiers: 9936817108331
Academic Unit: King Abdulaziz University; King Abdullah University of Science & Technology
Language: English
Resource Type: Journal article