Wang Ying, Kanai Masahiro, Tan Taotao, Kamariza Mireille, Tsuo Kristin, Yuan Kai, Zhou Wei, Okada Yukinori, Huang Hailiang, Turley Patrick, Atkinson Elizabeth G, Martin Alicia R
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
Stanley Center for Psychiatric Research and Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Cell Genom. 2023 Sep 14;3(10):100408. doi: 10.1016/j.xgen.2023.100408. eCollection 2023 Oct 11.
Polygenic risk scores (PRSs) developed from multi-ancestry genome-wide association studies (GWASs), PRS, 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 compared with PRSs constructed from single-ancestry GWASs (PRS). Through extensive simulations and empirical analyses, we showed that PRS overall outperformed PRS 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-enriched variants. Our work highlights the importance of diversifying genomic studies to achieve equitable PRS performance across ancestral populations and provides guidance for developing PRSs from multiple studies.
从多血统全基因组关联研究（GWAS）中开发的多基因风险评分（PRS）有望提高PRS在不同人群中的准确性和通用性。为了确立利用基因组研究日益增长的多样性的最佳实践，我们研究了与从单血统GWAS构建的PRS相比，各种因素如何影响PRS的性能。通过广泛的模拟和实证分析，我们表明，除了研究不足的人群在多血统GWAS中所占比例较小时，PRS在研究不足的人群中总体表现优于PRS。此外，整合基于本地血统信息的GWAS和大规模欧洲血统PRS的PRS提高了在研究不足的非洲人群中的预测性能，特别是对于具有大效应血统富集变异的较少多基因性状。我们的工作强调了使基因组研究多样化以在不同祖先群体中实现公平的PRS性能的重要性，并为从多项研究中开发PRS提供了指导。
