Abstract

ObjectivesTo investigate the degree by which the inherited susceptibility to obesity is modified by environmental factors during childhood and adolescence. DesignCohort study with repeated measurements of diet, lifestyle factors and anthropometry. SettingThe pan-European IDEFICS/I.Family cohort Participants8,609 repeated observations from 3,098 children aged 2 to 16 years, examined between 2007 and 2014. Main outcome measuresBody mass index (BMI) and waist circumference. Genome-wide polygenic risk scores (PRS) to capture the inherited susceptibility of obesity were calculated using summary statistics from independent genome-wide association studies of BMI. Gene-environment interactions of the PRS with sociodemographic (European region, socioeconomic status) and lifestyle factors (diet, screen time, physical activity) were estimated. ResultsThe PRS was strongly associated with BMI (r2 = 0.11, p-value = 7.9 x 10-81) and waist circumference (r2 = 0.09, p-value = 1.8 x 10-71) in our cohort. The associations with BMI increased from r2=0.03 in 3-year olds to r2=0.18 in 14-year olds and associations with waist circumference from r2=0.03 to r2=0.14. Being in the top decile of the PRS distribution was associated with 3.63 times higher odds for obesity (95% confidence interval (CI): [2.57, 5.14]). We observed significant interactions with demographic and lifestyle factors for BMI as well as waist circumference. The risk of becoming obese among those with higher genetic susceptibility was ~38% higher in children from Southern Europe (BMI: p-interaction = 0.0066, Central vs. Southern Europe) and ~61% higher in children with a low parental education (BMI: p-interaction = 0.0012, low vs. high). Furthermore, the risk was attenuated by a higher intake of dietary fiber (BMI: p-interaction=0.0082) and shorter screen times (BMI: p-interaction=0.018). ConclusionsOur results highlight that a healthy childhood environment might partly offset a genetic predisposition to obesity during childhood and adolescence.