國家衛生研究院 NHRI:Item 3990099045/15383
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    题名: Fine-mapping across diverse ancestries drives the discovery of putative causal variants underlying human complex traits and diseases
    作者: Yuan, K;Longchamps, RJ;Pardiñas, AF;Yu, M;Chen, TT;Lin, SC;Chen, Y;Lam, M;Liu, R;Xia, Y;Guo, Z;Shi, W;Shen, C;Daly, MJ;Neale, BM;Feng, YA;Lin, YF;Chen, CY;O'Donovan, M;Ge, T;Huang, H
    贡献者: Center for Neuropsychiatric Research
    摘要: 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 ancestries 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, which builds on the single-population fine-mapping framework, Sum of Single Effects (SuSiE). SuSiEx integrates data from an arbitrary number of ancestries, explicitly models population-specific allele frequencies and LD patterns, accounts for multiple causal variants in a genomic region, and can be applied to GWAS summary statistics. We comprehensively evaluated SuSiEx using simulations, a range of quantitative traits measured in both UK Biobank and Taiwan Biobank, and schizophrenia GWAS across East Asian and European ancestries. In all evaluations, SuSiEx fine-mapped more association signals, produced smaller credible sets and higher posterior inclusion probability (PIP) for putative causal variants, and captured population-specific causal variants.
    日期: 2023-07-09
    關聯: medRxiv. 2023 Jul 9;Article in Press.
    Link to: http://dx.doi.org/10.1101/2023.01.07.23284293
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