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.

Background Prenatal chemical exposures may adversely affect neurodevelopment, but few studies have examined the persistence of these associations. We examined whether associations between prenatal bisphenol A (BPA) or polybrominated diphenyl ether (PBDE) exposures persist or resolve as children age. Methods We followed 346 mother-child pairs (enrolled 2003–2006) from Cincinnati, OH from pregnancy until children were 8 years old. We measured BPA in urine collected at 16 and 26 weeks gestation and PBDE-47 in serum collected at 16 weeks gestation. We administered repeated measures of children’s behavior, mental/psychomotor development, and IQ from ages 1–8 years. We determined if associations of BPA or PBDE-47 with child neurobehavior persisted or resolved as children aged using linear mixed models and estimated neurobehavioral measure reproducibility using intraclass correlation coefficients (ICCs). Results Higher BPA in girls and higher PBDE-47 in both boys and girls were associated with more externalizing behaviors; these associations persisted from ages 2–8 years (exposure × age interaction p-values≥0.36). Higher PBDE-47 concentrations were associated with decreases in MDI from ages 1–3 years (PBDE-47 × age interaction p-value=0.03) and persistently lower IQ at ages 5 and 8 years (PBDE-47 × age interaction p-value=0.56). Mental/psychomotor abilities had fair reproducibility from ages 1–3 years (ICCs~0.4), cognitive abilities from ages 5 to 8 years had excellent reproducibility (ICCs=0.7–0.8), and parent-reported behaviors from ages 2–8 years had poor to good reproducibility (ICCs=0.38–0.59). Conclusions Prenatal BPA and PBDE-47 concentrations were persistently associated with more externalizing behaviors. PBDE-47 concentrations were inversely associated with cognitive abilities that strengthened over time.

Clinically relevant weight loss is achievable through lifestyle modification, but unintentional weight regain is common. We investigated whether recently discovered genetic variants affect weight loss and/or weight regain during behavioral intervention. Participants at high-risk of type 2 diabetes (Diabetes Prevention Program [DPP]; N = 917/907 intervention/comparison) or with type 2 diabetes (Look AHEAD [Action for Health in Diabetes]; N = 2,014/1,892 intervention/comparison) were from two parallel arm (lifestyle vs. comparison) randomized controlled trials. The associations of 91 established obesity-predisposing loci with weight loss across 4 years and with weight regain across years 2–4 after a minimum of 3% weight loss were tested. Each copy of the minor G allele of MTIF3 rs1885988 was consistently associated with greater weight loss following lifestyle intervention over 4 years across the DPP and Look AHEAD. No such effect was observed across comparison arms, leading to a nominally significant single nucleotide polymorphism×treatment interaction (P = 4.3 × 10−3). However, this effect was not significant at a study-wise significance level (Bonferroni threshold P < 5.8 × 10−4). Most obesity-predisposing gene variants were not associated with weight loss or regain within the DPP and Look AHEAD trials, directly or via interactions with lifestyle.