查看文章

Polygenic risk scores (PRSs) developed from multi-ancestry genome-wide association studies (GWASs), PRS_multi, hold promise for improving PRS accuracy and generalizability across populations. To establish best practices for leveraging the increasing diversity of genomic studies, we investigated how various factors affect the performance of PRS_multi compared with PRSs constructed from single-ancestry GWASs (PRS_single). Through extensive simulations and empirical analyses, we showed that PRS_multi overall outperformed PRS_single in understudied populations, except when the understudied population represented a small proportion of the multi-ancestry GWAS. Furthermore, integrating PRSs based on local ancestry-informed GWASs and large-scale, European-based PRSs improved predictive performance in understudied African populations, especially for less polygenic traits with large-effect ancestry …