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Journal articles

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

Tuomas O. Kilpeläinen ¹ Lu Qi ^{2, *} Soren Brage ¹ Stephen J. Sharp ¹ Emily Sonestedt ³ Ellen Demerath ⁴ Tariq Ahmad ⁵ Samia Mora ⁶ Marika Kaakinen ⁷ Camilla Helene Sandholt ⁸ Christina Holzapfel ^{9, 10} Christine S. Autenrieth ¹¹ Elina Hyppönen ^{12, 13} Stéphane Cauchi ¹⁴ Meian He ¹⁵ Zoltan Kutalik ¹⁶ Meena Kumari ¹⁷ Alena Stančáková ¹⁸ Karina Meidtner ¹⁹ Beverley Balkau ²⁰ Jonathan T. Tan ²¹ Massimo Mangino ²² Nicholas J. Timpson ²³ yiqing Song ²⁴ M Carola Zillikens ^{25, 26} Kathleen A. Jablonski ²⁷ Melissa E. Garcia ²⁸ Stefan Johansson ^{29, 30} Jennifer L. Bragg-Gresham ³¹ ying Wu ³² Jana V. van Vliet-Ostaptchouk ³³ N Charlotte Onland-Moret ^{34, 35} Esther Zimmermann ^{36, 37} Natalia V. Rivera ³⁸ Toshiko Tanaka ^{28, 39} Heather M. Stringham ³¹ Günther Silbernagel ⁴⁰ Stavroula Kanoni ⁴¹ Mary F. Feitosa ⁴² Soren Snitker ⁴³ Jonatan R. Ruiz ^{44, 45} Jeffery Metter ²⁸ Maria Teresa Martinez Larrad ⁴⁶ Mustafa Atalay ⁴⁷ Maarit Hakanen ⁴⁸ Najaf Amin ³⁸ Christine Cavalcanti-Proença ¹⁴ Anders Grøntved ⁴⁹ Göran Hallmans ⁵⁰ John-Olov Jansson ⁵¹ Johanna Kuusisto ¹⁸ Mika Kähönen ⁵² Pamela L. Lutsey ⁴ John J. Nolan ⁵³ Luigi Palla ¹ Oluf Pedersen ^{8, 36, 54, 55} Louis Pérusse ⁵⁶ Frida Renström ^{2, 3, 56} Robert A. Scott ¹ Dmitry Shungin ^{3, 56, 57} Ulla Sovio ⁵⁸ Tuija H. Tammelin ^{59, 60} Tapani Rönnemaa ⁶¹ Timo A. Lakka ⁴⁷ Matti Uusitupa ⁶² Manuel Serrano Rios ⁴⁶ Luigi Ferrucci ³⁹ Claude Bouchard ⁶³ Aline Meirhaeghe ⁶⁴ Mao Fu ⁶⁵ Mark Walker ⁶⁶ Ingrid B. Borecki ⁴² George V. Dedoussis ⁴¹ Andreas Fritsche ⁴⁰ Claes Ohlsson ⁶⁷ Michael Boehnke ³¹ Stefania Bandinelli ⁶⁸ Cornelia M. van Duijn ^{26, 38, 69} Shah Ebrahim ⁷⁰ Debbie A. Lawlor ²³ Vilmundur Gudnason ^{71, 72} Tamara B. Harris ²⁸ Thorkild I. A. Sørensen ³⁶ Karen L. Mohlke ³² Albert Hofman ^{26, 38} André G. Uitterlinden ^{25, 26, 38} Jaakko Tuomilehto ^{73, 74, 75} Terho Lehtimäki ⁷⁶ Olli Raitakari ^{48, 77} Bo Isomaa ^{78, 79} Pål R. Njølstad ³⁰ Jose C. Florez ^{80, 81, 82} Simin Liu ⁸³ Andy Ness ⁸⁴ Timothy D. Spector ²² E Shyong Tai ⁸⁵ Philippe Froguel ^{14, 86} Heiner Boeing ¹⁹ Markku Laakso ¹⁸ Michael Marmot ⁸⁷ Sven Bergmann ¹⁶ Chris Power ¹² Kay-Tee Khaw ⁸⁸ Daniel Chasman ⁶ Paul Ridker ⁶ Torben Hansen ^{8, 54, 89} Keri L. Monda ⁹⁰ Thomas Illig ¹⁰ Marjo-Riitta Järvelin ^{7, 91, 92} Nicholas J. Wareham ¹ Frank B. Hu ¹⁵ Leif C. Groop ³ Marju Orho-Melander ³ Ulf Ekelund ¹ Paul W. Franks ^{2, 3, 56, *} Ruth J. F. Loos ^{1, *}

* Corresponding author

1 Institute of Metabolic Science

2 Departments of Epidemiology and Nutrition

3 Department of Clinical Sciences

4 Division of Epidemiology and Community Health

5 Division of Cardiology

6 Brigham and Women's Hospital [Boston]

7 Institute of Health Sciences and Biocenter Oulu

8 Hagedorn Research Institute

9 ZIEL - Else Kroener Fresenius Centre - Zentralinstitut für Ernährungs und Lebensmittelfors

10 Department of Population Health Sciences

11 EPI - Institute of Epidemiology [Neuherberg]

12 Centre for Paediatric Epidemiology and Biostatistics

13 MRC Centre for Epidemiology of Child Health

14 IBL - Institut de biologie de Lille - UMS 3702

15 Harvard School of Public Health

16 Department of Medical Genetics

17 Department of Epidemiology and Public Health

18 Department of Medicine

19 Department of Epidemiology

20 CESP - Centre de recherche en épidémiologie et santé des populations

21 Department of Epidemiology and Public Health

22 King‘s College London

23 Centre for Causal Analyses in Translational Epidemiology

24 Division of Preventive Medicine

25 Netherlands Genomics Initiative

26 Department of Internal Medicine

27 The Biostatistics Center

28 NIA - National Institute on Aging [Bethesda, USA]

29 Mental Health Sciences Unit

30 Department of Clinical Medicine

31 Department of Biostatistics and Center for Statistical Genetics

32 Department of Genetics

33 Molecular Genetics Section

34 Complex Genetics Section

35 Julius Center for Health Sciences and Primary Care

36 Institute of Preventive Medicine

37 Department of Biomedical Sciences [Copenhagen]

38 Genetic Epidemiology Unit

39 Medstar Research Institute

40 Division of Endocrinology, Diabetology, Nephrology, Vascular Disease, and Clinical Chemistry

41 Department of Nutrition-Dietetics

42 Division of Statistical Genomics

43 University of Maryland School of Medicine

44 Unit for Preventive Nutrition

45 Department of Physical Education and Sport

46 Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas

47 Department of Physiology

48 The Research Centre of Applied and Preventive Cardiovascular Medicine

49 Institute of Sport Science and Clinical Biomechanics

50 Department of Public Health and Clinical Medicine/Nutritional Research

51 Department of Physiology/Endocrinology

52 Department of Clinical Physiology

53 Steno Diabetes Centre

54 CBMR - Novo Nordisk Foundation Center for Basic Metabolic Research

55 Faculty of Health Sciences

56 Genetic Epidemiology and Clinical Research Group

57 Department of Odontology

58 Department of Medical Statistics

59 LIKES Research Center for Sport and Health Sciences

60 Finnish Institute of Occupational Health

61 Department of Medicine

62 Institute of Public Health and Clinical Nutrition

63 Human Genomics Laboratory

64 Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations

65 Division of Endocrinology, Diabetes and Nutrition

66 Institute of Cell and Molecular Biosciences

67 Centre for Bone and Arthritis Research

68 Geriatric Rehabilitation Unit

69 Netherlands Genomics Initiative

70 Faculty of Epidemiology and Population Health [London]

71 Icelandic Heart Association

72 University of Iceland [Reykjavik]

73 Department of Public Health

74 South Ostrobothnia Central Hospital

75 Department of Clinical and Preventive Medicine

76 Department of Clinical Chemistry

77 Department of Clinical Physiology

78 Folkhälsan Research Centre

79 Department of Pediatrics

80 Center for Human Genetic Research and Diabetes Research Center

81 Department of Medicine

82 Program for Medical and Population Genetics

83 Center for Metabolic Disease Prevention

84 School of Oral and Dental Sciences

85 Department of Medicine

86 Department of Genomics of Common Disease

87 Department of Epidemiology and Public Health

88 Department of Public Health and Primary Care

89 Faculty of Health Sciences

90 Department of Epidemiology

91 Department of Epidemiology and Biostatistics

92 Department of Life Course and Services

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 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.

Document type :

Journal articles

Domain :

Life Sciences [q-bio] / Santé publique et épidémiologie

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