Genetic risk score predicts risk for overweight and obesity in Finnish preadolescents.

Common genetic variants predispose to obesity with varying contribution by age. We incorporated known genetic variants into genetic risk scores (GRSs) and investigated their associations with overweight/obesity and central obesity in preadolescents. Furthermore, we compared GRSs with lifestyle factors, and tested if they predict the change in body size and shape in a 4-year follow-up. We utilized 1142 subjects from the Finnish Health in Teens (Fin-HIT) cohort. Overweight and obesity were defined with age- and gender-specific body mass index (BMI) z-score (BMIz), while central obesity by the waist-to-height ratio (WHtR). Background data on parental language, eating habits, leisure-time physical activity (LTPA) and sleep duration were included. Genotyping was performed with the Metabochip platform. Weighted, standardized GRSs were derived. Of the11-year-old children, 25.5% were at least overweight and 90.8% had Finnish speaking background. BMI-GRS was associated with higher risk for overweight with odds ratio (95% confidence interval) of 1.39 (1.20; 1.60) and obesity 1.41 (1.08; 1.83), but not with central obesity. BMI-GRS was weakly and inversely associated with the changes in BMIz and WHtR in the 4-year follow-up. Waist-to-hip ratio-GRS was not related to any obesity measures at baseline nor in the follow-up. The effect of BMI-GRS is similar to that of low LTPA on overweight. An interaction between parental language and BMI-GRS was noted (P = .019): BMI-GRS associated more strongly with overweight in Swedish than in Finnish speakers. We further identified two suggestive genetic variants near LOC101926977 and LOC105369677 associated with BMIz in preadolescents which were replicated in the adult population. In preadolescents, known genetic predisposing factors induce a risk for overweight comparable to low LTPA. However, the GRS was poor in predicting short-term changes in BMI or WHtR.