title: FTO genotype and weight loss: systematic review and meta-analysis of 9563 individual participant data from eight randomised controlled trials.
abstract: OBJECTIVE
  To assess the effect of the FTO genotype on weight loss after dietary, physical activity, or drug based interventions in randomised controlled trials.
  
  
  METHODS
  Systematic review and random effects meta-analysis of individual participant data from randomised controlled trials.
  
  
  METHODS
  Ovid Medline, Scopus, Embase, and Cochrane from inception to November 2015.
  
  
  METHODS
  Randomised controlled trials in overweight or obese adults reporting reduction in body mass index, body weight, or waist circumference by FTO genotype (rs9939609 or a proxy) after dietary, physical activity, or drug based interventions. Gene by treatment interaction models were fitted to individual participant data from all studies included in this review, using allele dose coding for genetic effects and a common set of covariates. Study level interactions were combined using random effect models. Metaregression and subgroup analysis were used to assess sources of study heterogeneity.
  
  
  RESULTS
  We identified eight eligible randomised controlled trials for the systematic review and meta-analysis (n=9563). Overall, differential changes in body mass index, body weight, and waist circumference in response to weight loss intervention were not significantly different between FTO genotypes. Sensitivity analyses indicated that differential changes in body mass index, body weight, and waist circumference by FTO genotype did not differ by intervention type, intervention length, ethnicity, sample size, sex, and baseline body mass index and age category.
  
  
  CONCLUSIONS
  We have observed that carriage of the FTO minor allele was not associated with differential change in adiposity after weight loss interventions. These findings show that individuals carrying the minor allele respond equally well to dietary, physical activity, or drug based weight loss interventions and thus genetic predisposition to obesity associated with the FTO minor allele can be at least partly counteracted through such interventions.
  
  
  BACKGROUND
  PROSPERO CRD42015015969.
authors.affiliation: Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE4 5PL, UK Deakin University, Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Victoria, Australia.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Livingstone
authors.affiliation: Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE4 5PL, UK BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Science, University of Glasgow, Glasgow, UK.
authors.forename: Carlos
authors.initials: C
authors.lastname: Celis-Morales
authors.affiliation: Department of Biostatistics, Brown University School of Public Health, Providence, RI, USA.
authors.forename: George D
authors.initials: GD
authors.lastname: Papandonatos
authors.affiliation: Department of Biostatistics, Brown University School of Public Health, Providence, RI, USA.
authors.forename: Bahar
authors.initials: B
authors.lastname: Erar
authors.affiliation: Diabetes Unit and Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA Programs in Metabolism and Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
authors.forename: Jose C
authors.initials: JC
authors.lastname: Florez
authors.affiliation: George Washington University Department of Epidemiology and Biostatistics The Biostatistics Center, Rockville, MD, USA.
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Jablonski
authors.affiliation: Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain CIBER Fisiopatologia de la Obesidad y Nutricion and PREDIMED Network from Instituto de Salud Carlos III Spanish Government, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Razquin
authors.affiliation: CIBER Fisiopatologia de la Obesidad y Nutricion and PREDIMED Network from Instituto de Salud Carlos III Spanish Government, Spain Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Spain.
authors.forename: Amelia
authors.initials: A
authors.lastname: Marti
authors.affiliation: Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA.
authors.forename: Yoriko
authors.initials: Y
authors.lastname: Heianza
authors.affiliation: Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA Epidemiology Domain, Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
authors.forename: Tao
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authors.lastname: Huang
authors.affiliation: Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Frank M
authors.initials: FM
authors.lastname: Sacks
authors.affiliation: Novo Nordisk Foundation Centre for Basic Metabolic Research, Section on Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark Danish Diabetes Academy, Odense, Denmark.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Svendstrup
authors.affiliation: Department of Exercise Science, University of South Carolina, Columbia, SC, USA.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Sui
authors.affiliation: Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, USA.
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Church
authors.affiliation: Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland Department of Medical and Clinical Genetics, University of Helsinki, Finland.
authors.forename: Tiina
authors.initials: T
authors.lastname: Jääskeläinen
authors.affiliation: Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Jaana
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authors.affiliation: Dasman Diabetes Institute, Dasman, Kuwait City, Kuwait Diabetes Research Group, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Jaakko
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authors.lastname: Tuomilehto
authors.affiliation: Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
authors.forename: Matti
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authors.lastname: Uusitupa
authors.affiliation: Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, USA.
authors.forename: Tuomo
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authors.lastname: Rankinen
authors.affiliation: Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre +, Maastricht, Netherlands.
authors.forename: Wim H M
authors.initials: WH
authors.lastname: Saris
authors.affiliation: Novo Nordisk Foundation Centre for Basic Metabolic Research, Section on Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Torben
authors.initials: T
authors.lastname: Hansen
authors.affiliation: Novo Nordisk Foundation Centre for Basic Metabolic Research, Section on Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Oluf
authors.initials: O
authors.lastname: Pedersen
authors.affiliation: Department of Nutrition, Exercise and Sports, Copenhagen University, Rolighedsvej 30, Frederiksberg C, Denmark.
authors.forename: Arne
authors.initials: A
authors.lastname: Astrup
authors.affiliation: Novo Nordisk Foundation Centre for Basic Metabolic Research, Section on Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark Institute of Preventive Medicine, Bispebjerg and Frederiksberg Hospitals, The Capital Region, Denmark.
authors.forename: Thorkild I A
authors.initials: TI
authors.lastname: Sørensen
authors.affiliation: Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Qi
authors.affiliation: Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, USA.
authors.forename: George A
authors.initials: GA
authors.lastname: Bray
authors.affiliation: CIBER Fisiopatologia de la Obesidad y Nutricion and PREDIMED Network from Instituto de Salud Carlos III Spanish Government, Spain Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Martinez-Gonzalez
authors.affiliation: CIBER Fisiopatologia de la Obesidad y Nutricion and PREDIMED Network from Instituto de Salud Carlos III Spanish Government, Spain Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Spain Food Science and Physiology, Centre for Nutrition Research, University of Navarra, Pamplona, Spain.
authors.forename: J Alfredo
authors.initials: JA
authors.lastname: Martinez
authors.affiliation: Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Skåne University Hospital Malmö, Malmö, Sweden.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Franks
authors.affiliation: The Miriam Hospital and the Alpert School of Medicine, Brown University, Providence, USA.
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: McCaffery
authors.affiliation: Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE4 5PL, UK Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, UK.
authors.forename: Jose
authors.initials: J
authors.lastname: Lara
authors.affiliation: Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE4 5PL, UK john.mathers@newcastle.ac.uk.
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authors.lastname: Mathers
mesh_terms: D050154:Adiposity / Q000235:genetics; D000483:Alleles; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D009765:Obesity / Q000178:diet therapy* / Q000235:genetics*; D016032:Randomized Controlled Trials as Topic; D015431:Weight Loss / Q000235:genetics*
chemical_list: D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human