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新方法改进对不同祖先人群的多基因预测
2022-05-08 23:11

美国博德研究所Tian Ge等研究人员合作改进对不同祖先人群的多基因预测。相关论文于2022年5月5日在线发表在《自然—遗传学》杂志上。

据研究人员介绍,多基因风险评分(PRS)的跨人群预测性能逐渐减弱。由于现有的全基因组关联研究(GWAS)主要是在欧洲人后裔中进行的,PRS的有限可转移性降低了其在非欧洲人群中的临床价值,并可能加剧医疗保健方面的差距。最近在基因组研究中为平衡血统不平衡所做的努力扩大了非欧洲人GWAS的规模,尽管大多数仍然力量不足。
 
研究人员提出了一种新的PRS构建方法,即PRS-CSx,它通过整合多个人群的GWAS汇总统计资料来提高跨人群的多基因预测能力。PRS-CSx通过一个共享的连续收缩(CS)先验来耦合不同种群的遗传效应,通过共享摘要统计之间的信息和利用发现样本之间的连锁不平衡多样性来实现更准确的效应大小估计,同时继承了PRS-CS的计算效率和稳健性。结果表明,在模拟中,PRS-CSx在具有广泛的遗传结构、跨种群遗传重叠并且发现GWAS样本量的性状方面优于其他方法,并改善了对非欧洲人群的定量性状和精神分裂症风险的预测。
 
附:英文原文
 
Title: Improving polygenic prediction in ancestrally diverse populations

Author: Ruan, Yunfeng, Lin, Yen-Feng, Feng, Yen-Chen Anne, Chen, Chia-Yen, Lam, Max, Guo, Zhenglin, He, Lin, Sawa, Akira, Martin, Alicia R., Qin, Shengying, Huang, Hailiang, Ge, Tian

Issue&Volume: 2022-05-05

Abstract: Polygenic risk scores (PRS) have attenuated cross-population predictive performance. As existing genome-wide association studies (GWAS) have been conducted predominantly in individuals of European descent, the limited transferability of PRS reduces their clinical value in non-European populations, and may exacerbate healthcare disparities. Recent efforts to level ancestry imbalance in genomic research have expanded the scale of non-European GWAS, although most remain underpowered. Here, we present a new PRS construction method, PRS-CSx, which improves cross-population polygenic prediction by integrating GWAS summary statistics from multiple populations. PRS-CSx couples genetic effects across populations via a shared continuous shrinkage (CS) prior, enabling more accurate effect size estimation by sharing information between summary statistics and leveraging linkage disequilibrium diversity across discovery samples, while inheriting computational efficiency and robustness from PRS-CS. We show that PRS-CSx outperforms alternative methods across traits with a wide range of genetic architectures, cross-population genetic overlaps and discovery GWAS sample sizes in simulations, and improves the prediction of quantitative traits and schizophrenia risk in non-European populations. 

DOI: 10.1038/s41588-022-01054-7

Source: https://www.nature.com/articles/s41588-022-01054-7

Nature Genetics:《自然—遗传学》,创刊于1992年。隶属于施普林格·自然出版集团,最新IF:41.307
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex


本期文章:《自然—遗传学》:Online/在线发表

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