ABSTRACT Introduction Polygenic risk scores (PRS) stratify obesity risk in population cohorts, but their value within specialised paediatric obesity clinics—where genetic liability may already be saturated—remains unclear. Methods We analysed 246 European adolescents with overweight and obesity (mean ± SD age 13.3 ± 2.2 years; 51% female; BMI 31.6 ± 4.1 kg/m 2 ) attending a tertiary clinic in Salzburg, Austria. BMI‐PRS based on people with European ancestry (PGS000027) and two cardiometabolic PRS (Homeostasis Model Assessment of Insulin Resistance HOMA‐IR, type 2 diabetes T2D) were computed from Axiom‐array genotypes. Distributions were compared with a population‐based adult cohort from the same region ( n = 2044). Associations with BMI, insulin resistance (HOMA‐IR ≥ 2.5), alanine aminotransferase (ALT) and oral‐glucose‐tolerance parameters were examined by linear and logistic regression adjusted for age and sex. Results The adolescent cohort showed a right‐shifted BMI‐PRS distribution; the lowest quintile exceeded the adult mean ( p < 0.001). Within the clinic sample, BMI‐PRS neither correlated with BMI ( r = −0.11; 95% CI −0.23 to 0.02) nor predicted other parameters investigated. PRS for HOMA‐IR and T2D showed similarly null associations. Conclusions In a genetically enriched clinical cohort, polygenic scores lose discriminatory power, delineating their optimal use for population screening rather than intra‐clinic risk stratification. These data underscore the strong hereditary architecture of paediatric obesity and support context‐specific application of precision‐medicine tools.
Gomahr et al. (Wed,) studied this question.
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