FTO Genotype And Body Mass Index In Young Children: Physical Activity Levels Influence The Effect Of The Risk Genotype

Abstract

Modifiable lifestyle factors such as levels of physical activity have been shown to be associated with body mass index (BMI). Recent studies have also shown that a number of gene loci are associated with variation in BMI. The IDEFICS study with a cohort size of 16,223 young children is one of the largest single studies in the pre-adult life stages to undertake saliva/DNA collection in conjunction with extensive phenotypic assessment and is therefore well-suited for studying the interaction between genes, physical activity and adiposity. PURPOSE: To investigate environmental and genetic associations on BMI in European children. METHODS: Anthropometric measurements (including adiposity) and objectively measured physical activity using accelerometry were assessed in a subgroup of children (n=4678) aged 2-10 years from the IDEFICS study. DNA from saliva samples was generated for genotyping. Here we report associations between BMI, selected physical activity measures and the FTO gene (rs9939609) as assessed using GLM and regression models. RESULTS: Clear effects on BMI were observed with time spent in sedentary behaviors (P < 0.0001), physical activity levels as counts per minute (P < 0.0001) and time spent in vigorous physical activity (P < 0.0001). Gender differences were observed for all these activity measures. FTO (SNP rs9939609) was found to influence age- and gender-adjusted BMI (P=2.0 × 10-5), genotype explaining 0.5% of the BMI variance. However, the strength of this association was marginal after further adjustment for main effects of physical activity. No interaction was observed between physical activity and FTO and the reduced effect of FTO in the models incorporating activity measures was not explained by association between FTO and physical activity. CONCLUSION: These preliminary results confirm previous associations between the FTO gene and adiposity in a cohort of European children aged between 2 and 10 years, but highlight the need to adjust for levels of physical activity when estimating the genotype effects on obesity risk.