FTO genotype and weight loss: a systematic review and meta-analysis of 9,563 individual participant data from eight randomized controlled trials

Objective - The objective of this study was to assess the effect of FTO genotype on weight loss following dietary, exercise or drug-based intervention in randomized controlled trials (RCTs). Design - Systematic review and random effects meta-analysis of individual participant data from randomized controlled trials. Data sources - Ovid Medline, Scopus, Embase and Cochrane were searched between inception and November 2015. Eligibility criteria for selecting studies - Randomized controlled trials in overweight or obese adults reporting reduction in BMI, body weight, and/or waist circumference (WC) by FTO genotype (rs9939609 or a proxy) following dietary, physical activity or drug based interventions. Gene by treatment interaction models were fit 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. Meta-regression and subgroup analysis were used to assess sources of study heterogeneity. Results - We identified 8 eligible RCTs for the systematic review and meta-analysis (n=9563). Overall, differential changes in BMI, body weight and WC in response to weight loss intervention were not significantly different between FTO genotypes. Sensitivity analyses indicated that differential changes in BMI, body weight and WC by FTO genotype did not differ by intervention type, intervention length, ethnicity, sample size, sex and baseline BMI and age category. Conclusions - We have observed that carriage of the FTO minor allele was not associated with differential change in adiposity following 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 FTO minor allele can be at least partly counteracted through such interventions.