Influence of common variants near INSIG2, in FTO, and near MC4R genes on overweight and the metabolic profile in adolescence: the TRAILS (TRacking Adolescents ’ Individual Lives Survey) Study1–3

Background: Overweight is a complex trait in which both environ-mental and genetic factors play a role. Objective: We aimed to evaluate the influence of common genetic variants identified by genome-wide association studies on over-weight and the metabolic profile in adolescence. Design: In a population-based cohort of 663 girls and 612 boys aged 16 y, weight, height, skinfold thicknesses, percentage body fat, waist circumference, blood pressure, glucose, insulin, lipid pro-file, and DNA were obtained. We defined overweight according to international criteria. We performed multiple linear and logistic re-gression analyses to assess the influence of candidate single nucle-otide polymorphisms near the INSIG2, in the FTO, and near the MC4R genes and repeated-measures analyses of available body mass index (BMI) and skinfold thickness data across 3 visits at ages 11, 13.5, and 16 y. Results: A total of 15.1 % of participants were overweight or obese at age 16 y. No associations with INSIG2 were found. Common variation in the FTO gene was associated with sex-specific z score