The Role of Polygenic Risk Score in the General Population: Current Status and Future Prospects.

Abstract

Polygenic risk scores (PRSs), constructed from numerous common single nucleotide polymorphisms (SNPs), have emerged as useful tools for predicting future atherosclerotic cardiovascular disease (ASCVD). PRSs have shown independent associations with ASCVD outcomes and are increasingly being considered to enhance risk stratification and guide primary prevention strategies. However, most evidence to date has been derived from populations of European ancestry, and their generalizability to other populations, including East Asians, remains uncertain. This review summarizes the current epidemiological evidence on the association between PRS and ASCVD outcomes, focusing on findings in Japanese cohorts. We discuss the potential of PRS as a clinical decision support tool, its incremental value over traditional risk factors, and its role in the early identification of high-risk individuals. We also highlight the limited number of prospective studies in the Japanese population, where validation and implementation studies are ongoing. Given the growing accessibility of genetic testing and the potential of PRS to complement conventional risk assessments, further large-scale studies are warranted to evaluate its clinical utility across diverse populations. Expanding ancestry-specific biobanks and improving PRS transferability are essential steps toward the equitable implementation of genomic risk prediction in ASCVD prevention.