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在不同的血统中进行精细映射可以发现人类复杂特征和疾病背后的潜在因果变异。

Fine-mapping across diverse ancestries drives the discovery of putative causal variants underlying human complex traits and diseases.

机构信息

Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.

Stanley Center for Psychiatric Research, the Broad Institute of MIT and Harvard, Cambridge, MA, USA.

出版信息

Nat Genet. 2024 Sep;56(9):1841-1850. doi: 10.1038/s41588-024-01870-z. Epub 2024 Aug 26.

DOI:10.1038/s41588-024-01870-z
PMID:39187616
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11888783/
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.

摘要

全基因组关联研究(GWAS)常涉及跨越数百或数千个遗传变异的遗传位点,其中许多具有相似的统计学意义。虽然欧洲血统个体的统计精细映射取得了重要发现,但通过利用跨种族的基因组多样性,跨人群精细映射有可能提高功效和分辨率。本文介绍了 SuSiEx,这是一种用于跨人群精细映射的准确且计算效率高的方法。SuSiEx 整合了任意数量的种族数据,明确建模了特定人群的等位基因频率和连锁不平衡模式,考虑了基因组区域中多个因果变异,并可应用于 GWAS 汇总统计数据。我们使用模拟全面评估了 SuSiEx 的性能。我们进一步表明,SuSiEx 通过整合东亚和欧洲血统的 GWAS,改善了 UK Biobank 和台湾 Biobank 中多种数量性状的精细映射,并改善了精神分裂症相关位点的精细映射。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9306/11888783/bcc1b9a81f61/nihms-2047735-f0006.jpg
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