Assessment of polygenic risk score performance in East Asian populations for ten common diseases: A Korean cohort study

Abstract

Polygenic risk score (PRS) uses genetic variants to assess disease susceptibility. While PRS performance is well-studied in Europeans, its accuracy in East Asians is less explored. This study compared East Asian PRS-continuous shrinkage (PRS-CS) from single-population genome-wide association studies (GWAS) with transferability PRS (PRS-CSx) integrating European and East Asian GWAS for ten common diseases in the Health Examinees (HEXA) cohort (n = 55,870) in Korea. PRS-CSx showed significant transferability, improving predictive metrics: likelihood ratio test (LRT) [1.31-fold], odds ratio per 1 standard deviation (perSD OR) [1.04-fold], and net reclassification improvement (NRI) [1.24-fold]. The difference in R² values between PRS-CS and PRS-CSx, analyzed using the r2redux method, was statistically significant across eight diseases, demonstrating an average increase of 0.35% in R² for PRS-CSx. Additionally, we compared the relative performance of these East Asian PRSs with their respective European PRSs for seven diseases, resulting in an average performance of 85.69%. Our findings indicate that while transferability enhances the performance of East Asian PRSs, large-scale East Asian GWAS data are essential to bridge the performance gap with European PRSs for effective disease prediction in East Asian populations.