The Use of Body Mass Index Polygenic Risk Score (BMI-PRS) in a Paediatric Population With Obesity

Area of Science:

• Genetics
• Pediatrics
• Obesity Research

Background:

• Polygenic risk scores (PRS) are utilized to assess obesity risk in general populations.
• Their utility in specialized pediatric obesity clinics, where genetic predisposition may already be high, is uncertain.

Purpose of the Study:

• To evaluate the effectiveness of PRS in stratifying obesity risk within a specialized pediatric clinic.
• To compare PRS distributions in an adolescent clinical cohort with a general adult population.

Main Methods:

• Analysis of 246 European adolescents with overweight/obesity (mean age 13.3 years).
• Computation of Body Mass Index (BMI)-PRS, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) PRS, and type 2 diabetes (T2D) PRS from genotype data.
• Comparison of PRS distributions with a regional adult cohort (n=2044) and examination of associations with BMI and metabolic parameters.

Main Results:

• The adolescent clinic cohort exhibited a right-shifted BMI-PRS distribution compared to the adult population.
• BMI-PRS did not correlate with BMI or predict other metabolic parameters within the clinic sample.
• HOMA-IR and T2D PRS also showed no significant associations in this clinical cohort.

Conclusions:

• Polygenic risk scores demonstrate reduced discriminatory power in genetically enriched clinical pediatric obesity cohorts.
• PRS are more appropriate for population screening than for risk stratification within specialized clinics.
• Findings highlight the strong genetic basis of pediatric obesity and advocate for context-specific application of precision medicine.