Polygenic risk for obesity and its interaction with lifestyle and sociodemographic factors in European children and adolescents.

BACKGROUND: Childhood obesity is a complex multifaceted condition, which is influenced by genetics, environmental factors, and their interaction. However, these interactions have mainly been studied in twin studies and evidence from population-based cohorts is limited. Here, we analyze the interaction of an obesity-related genome-wide polygenic risk score (PRS) with sociodemographic and lifestyle factors for BMI and waist circumference (WC) in European children and adolescents. METHODS: The analyses are based on 8609 repeated observations from 3098 participants aged 2-16 years from the IDEFICS/I.Family cohort. A genome-wide polygenic risk score (PRS) was calculated using summary statistics from independent genome-wide association studies of BMI. Associations were estimated using generalized linear mixed models adjusted for sex, age, region of residence, parental education, dietary intake, relatedness, and population stratification. RESULTS: The PRS was associated with BMI (beta estimate [95% confidence interval (95%-CI)] = 0.33 [0.30, 0.37], r2 = 0.11, p value = 7.9 × 10-81) and WC (beta [95%-CI] = 0.36 [0.32, 0.40], r2 = 0.09, p value = 1.8 × 10-71). We observed significant interactions with demographic and lifestyle factors for BMI as well as WC. Children from Southern Europe showed increased genetic liability to obesity (BMI: beta [95%-CI] = 0.40 [0.34, 0.45]) in comparison to children from central Europe (beta [95%-CI] = 0.29 [0.23, 0.34]), p-interaction = 0.0066). Children of parents with a low level of education showed an increased genetic liability to obesity (BMI: beta [95%-CI] = 0.48 [0.38, 0.59]) in comparison to children of parents with a high level of education (beta [95%-CI] = 0.30 [0.26, 0.34]), p-interaction = 0.0012). Furthermore, the genetic liability to obesity was attenuated by a higher intake of fiber (BMI: beta [95%-CI] interaction = -0.02 [-0.04,-0.01]) and shorter screen times (beta [95%-CI] interaction = 0.02 [0.00, 0.03]). CONCLUSIONS: Our results highlight that a healthy childhood environment might partly offset a genetic predisposition to obesity during childhood and adolescence.