TY - JOUR

T1 - FTO genotype and weight loss

T2 - systematic review and meta-analysis of 9563 individual participant data from eight randomised controlled trials

AU - Livingstone, Katherine M

AU - Celis-Morales, Carlos

AU - Papandonatos, George D

AU - Erar, Bahar

AU - Florez, Jose C

AU - Jablonski, Kathleen A

AU - Razquin, Cristina

AU - Marti, Amelia

AU - Heianza, Yoriko

AU - Huang, Tao

AU - Sacks, Frank M

AU - Svendstrup, Mathilde

AU - Sui, Xuemei

AU - Church, Timothy S

AU - Jääskeläinen, Tiina

AU - Lindström, Jaana

AU - Tuomilehto, Jaakko

AU - Uusitupa, Matti

AU - Rankinen, Tuomo

AU - Saris, Wim H M

AU - Hansen, Torben

AU - Pedersen, Oluf

AU - Astrup, Arne

AU - Sørensen, Thorkild I.A.

AU - Lu, Qi

AU - Bray, George A.

AU - Martinez-Gonzalez, Miguel A

AU - Martinez, J Alfredo

AU - Franks, Paul W

AU - McCaffery, Jeanne M

AU - Lara, Jose

AU - Mathers, John C.

N1 - CURIS 2016 NEXS 260

PY - 2016

Y1 - 2016

N2 - OBJECTIVE: To assess the effect of the FTO genotype on weight loss after dietary, physical activity, or drug based interventions in randomised controlled trials.DESIGN: Systematic review and random effects meta-analysis of individual participant data from randomised controlled trials.DATA SOURCES: Ovid Medline, Scopus, Embase, and Cochrane from inception to November 2015.ELIGIBILITY CRITERIA FOR STUDY SELECTION: 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.SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015015969.

AB - OBJECTIVE: To assess the effect of the FTO genotype on weight loss after dietary, physical activity, or drug based interventions in randomised controlled trials.DESIGN: Systematic review and random effects meta-analysis of individual participant data from randomised controlled trials.DATA SOURCES: Ovid Medline, Scopus, Embase, and Cochrane from inception to November 2015.ELIGIBILITY CRITERIA FOR STUDY SELECTION: 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.SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015015969.

U2 - 10.1136/bmj.i4707

DO - 10.1136/bmj.i4707

M3 - Journal article

C2 - 27650503

VL - 354

JO - The BMJ

JF - The BMJ

SN - 0959-8146

M1 - i4707

ER -