The Use of Body Mass Index Polygenic Risk Score (BMI-PRS) in a Paediatric Population With Obesity.
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.
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/m2) 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.
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.
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.
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/m2) 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.
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.
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.
Authors
Gomahr Gomahr, Lauth Lauth, Süßenbacher Süßenbacher, Bergauer Bergauer, Forer Forer, Eberhardt Eberhardt, Schaffler-Schaden Schaffler-Schaden, Reiter Reiter, Mörwald Mörwald, Langthaler Langthaler, Iglseder Iglseder, Paulweber Paulweber, Flamm Flamm, Aigner Aigner, Trinka Trinka, Bito Bito, Kiesslich Kiesslich, Kedenko Kedenko, Wernly Wernly, Weghuber Weghuber
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