Cross-Population Analysis of Sjögren's Syndrome Polygenic Risk Scores and Disease Prevalence: A Pilot Study

Polygenic risk scores (PRS) have emerged as promising tools for disease risk stratification. However, their validity across different populations remains unclear, particularly for autoimmune diseases, where environmental factors may play crucial roles.

We calculated the population-level PRS for Sjögren's syndrome using seven validated genetic variants (PGS001308) and allele frequency data from the 1000 Genomes Project Phase 3 for five European populations (CEU, TSI, FIN, GBR, and IBS). PRS values were correlated with published prevalence estimates from a systematic literature review. Statistical analyses included Pearson's correlation and sensitivity analyses.

PRS values varied across European populations, ranging from 0.317 in the Spanish population to 0.370 in the Northern European population. A non-significant negative trend was observed between population PRS and Sjögren's syndrome prevalence (r = -0.407, R² = 0.166). Italy showed the lowest genetic risk score (TSI: 0.349) but the highest disease prevalence (58.2 per 100,000), while Northern European populations demonstrated a higher PRS but lower prevalence.

No significant correlation was found between genetic risk scores and disease prevalence in this limited sample of five European populations. Larger studies are needed to clarify the relationship between polygenic risk and disease prevalence.