Intergenerational polygenic obesity risk throughout adolescence in a cross-sectional study design: The HUNT study, Norway.

Abstract

This study examined the relationship between parental obesity polygenic risk and children's BMI throughout adolescence. Additionally, from a smaller subsample, the objective was to assess whether parental polygenic risk score (PRS) may act as a proxy for offspring PRS in studies lacking offspring genetic data. A total of 8,561 parent-offspring (age 13-19 years) trios from the Trøndelag Health Study (the HUNT Study) were included, of which, 1,286 adolescents had available genetic data. Weighted parental PRSs from 900 single-nucleotide polymorphisms robustly associated with adult BMI were constructed and applied in linear mixed-effects models. A positive association between parental PRS and offspring sex- and age-adjusted BMI (iso-BMI) throughout adolescence was identified. The estimated marginal effects per standard deviation increase in parental PRS were 0.26 (95% CI: 0.18-0.33), 0.36 (95% CI: 0.29-0.43), and 0.62 kg/m² (95% CI: 0.51-0.72) for maternal, paternal, and combined parental PRS, respectively. In subsample analyses, the magnitude of association of the parental PRS versus offspring PRS with iso-BMI in adolescents was similar. Parental PRS was consistently associated with offspring iso-BMI throughout adolescence. Results from subsample analyses support the use of parental PRS of obesity as a proxy for adolescent PRS in the absence of offspring genetic data.