跨越不同祖先的精細定位推動人類復雜性狀和疾病背后潛在因果變異體的發現

作者：小柯機器人 發布時間：2024/8/28 15:02:39

本期文章：《自然—遺傳學》：Online/在線發表

美國哈佛醫學院Hailiang Huang等研究人員合作發現，跨越不同祖先的精細定位推動人類復雜性狀和疾病背后潛在因果變異體的發現。相關論文于2024年8月26日在線發表在《自然—遺傳學》雜志上。

研究人員提出SuSiEx，一種準確且計算高效的跨群體精細定位方法。SuSiEx整合了任意數量的祖先數據，明確建模群體特異性的等位基因頻率和連鎖不平衡模式，考慮基因組區域內的多種因果變異，并可應用于全基因組關聯研究（GWAS）匯總統計數據。

研究人員通過模擬全面評估了SuSiEx的性能。此外，研究人員還展示了SuSiEx通過整合英國生物庫和臺灣省生物庫中的定量性狀數據，改進了這些性狀的精細定位，并通過整合東亞和歐洲祖先的GWAS數據，提升了與精神分裂癥相關位點的精細定位。

據悉，GWAS常常揭示出跨越數百或數千個遺傳變異的基因位點，其中許多變異體具有相似的統計顯著性。盡管在歐洲祖先個體中的統計精細定位已取得重要發現，但通過利用不同祖先的基因組多樣性，跨群體精細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

期刊信息

Nature Genetics：《自然—遺傳學》，創刊于1992年。隸屬于施普林格·自然出版集團，最新IF：41.307

官方網址：https://www.nature.com/ng/

投稿鏈接：https://mts-ng.nature.com/cgi-bin/main.plex