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.

Keywords

Humans, Male, Female, RISK ASSESSMENT, CHILD, ADOLESCENT, Risk Factors, Body Mass Index, Austria/epidemiology, Genetic Predisposition to Disease, Genetic Risk Score, Pediatric Obesity/genetics, Insulin Resistance/genetics, Diabetes Mellitus, Type 2/genetics, Multifactorial Inheritance