美国哈佛医学院Hailiang Huang等研究人员合作发现,跨越不同祖先的精细定位推动人类复杂性状和疾病背后潜在因果变异体的发现。相关论文于2024年8月26日在线发表在《自然—遗传学》杂志上。
研究人员提出SuSiEx,一种准确且计算高效的跨群体精细定位方法。SuSiEx整合了任意数量的祖先数据,明确建模群体特异性的等位基因频率和连锁不平衡模式,考虑基因组区域内的多种因果变异,并可应用于全基因组关联研究(GWAS)汇总统计数据。
研究人员通过模拟全面评估了SuSiEx的性能。此外,研究人员还展示了SuSiEx通过整合英国生物库和台湾省生物库中的定量性状数据,改进了这些性状的精细定位,并通过整合东亚和欧洲祖先的GWAS数据,提升了与精神分裂症相关位点的精细定位。
据悉,GWAS常常揭示出跨越数百或数千个遗传变异的基因位点,其中许多变异体具有相似的统计显著性。尽管在欧洲祖先个体中的统计精细定位已取得重要发现,但通过利用不同祖先的基因组多样性,跨群体精细定位有望提高研究的能力和分辨率。
附:英文原文
Title: Fine-mapping across diverse ancestries drives the discovery of putative causal variants underlying human complex traits and diseases
Author: Yuan, Kai, Longchamps, Ryan J., Pardias, Antonio F., Yu, Mingrui, Chen, Tzu-Ting, Lin, Shu-Chin, Chen, Yu, Lam, Max, Liu, Ruize, Xia, Yan, Guo, Zhenglin, Shi, Wenzhao, Shen, Chengguo, Daly, Mark J., Neale, Benjamin M., Feng, Yen-Chen A., Lin, Yen-Feng, Chen, Chia-Yen, ODonovan, Michael C., Ge, Tian, Huang, Hailiang
Issue&Volume: 2024-08-26
Abstract: Genome-wide association studies (GWAS) of human complex traits or diseases often implicate genetic loci that span hundreds or thousands of genetic variants, many of which have similar statistical significance. While statistical fine-mapping in individuals of European ancestry has made important discoveries, cross-population fine-mapping has the potential to improve power and resolution by capitalizing on the genomic diversity across ancestries. Here we present SuSiEx, an accurate and computationally efficient method for cross-population fine-mapping. SuSiEx integrates data from an arbitrary number of ancestries, explicitly models population-specific allele frequencies and linkage disequilibrium patterns, accounts for multiple causal variants in a genomic region and can be applied to GWAS summary statistics. We comprehensively assessed the performance of SuSiEx using simulations. We further showed that SuSiEx improves the fine-mapping of a range of quantitative traits available in both the UK Biobank and Taiwan Biobank, and improves the fine-mapping of schizophrenia-associated loci by integrating GWAS across East Asian and European ancestries.
DOI: 10.1038/s41588-024-01870-z
Source: https://www.nature.com/articles/s41588-024-01870-z
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