2026年1月5日，哈佛大学陈曾熙公共卫生学院Alkes L. Price小组在《自然—遗传学》杂志发表论文，宣布他们发现了MultiSuSiE在“我们所有人”全基因组测序数据中改进了多祖先群体的精细定位。

研究组提出MultiSuSiE，它是单一效应总和（Sum of Single Effects, SuSiE）的扩展，可以扩展到多个祖先，从而允许不同祖先的气候效应大小不同。课题组评估了来自课题组所有人的47000名非洲血统，36000名拉丁血统和116000名欧洲血统个体的MultiSuSiE主题全基因组测序数据。在模拟中，MultiSuSiE应用于Afr36k +Lat36k +Eur36k校准良好，获得的功率高于SuSiE应用于Eur109k的功率；与最近的多祖先方法（SuSiEx和MESuSiE）相比，MultiSuSiE具有更高的功率和更低的计算成本。在14个数量性状的分析中，MultiSuSiE应用于Afr47k +Lat36k +Eur116k识别出348个精细映射的变异，后验嵌套概率（PIP）为0.9，MultiSuSiE应用于Afr36k + Lat36k +Eur36k识别出的PIP>0.9变异比应用于Eur109k的SuSiE多59%；MultiSuSiE比SuSiEx多识别出29%的PIP >0.9变种，MESuSiE由于计算成本高而未被纳入。该课题组研究人员通过精细映射变异的功能富集验证了这些发现，并强调了涉及生物学上可移植的精细映射变异的例子。

据悉，利用多祖先数据可以提高精细映射的能力。

附：英文原文

Title: MultiSuSiE improves multi-ancestry fine-mapping in All of Us whole-genome sequencing data

Author: Rossen, Jordan, Shi, Huwenbo, Strober, Benjamin J., Zhang, Martin Jinye, Kanai, Masahiro, McCaw, Zachary R., Liang, Liming, Weissbrod, Omer, Price, Alkes L.

Issue&Volume: 2026-01-05

Abstract: Leveraging multi-ancestry data can improve fine-mapping power. We propose MultiSuSiE, an extension of Sum of Single Effects (SuSiE), to multiple ancestries that allows causal effect sizes to vary across ancestries. We evaluated MultiSuSiE using whole-genome sequencing data from 47,000 African-ancestry, 36,000 Latino-ancestry and 116,000 European-ancestry individuals from All of Us. In simulations, MultiSuSiE applied to Afr36k+Lat36k+Eur36k was well-calibrated and attained higher power than SuSiE applied to Eur109k; compared to recent multi-ancestry methods (SuSiEx and MESuSiE), MultiSuSiE attained higher power and lower computational cost. In analyses of 14 quantitative traits, MultiSuSiE applied to Afr47k+Lat36k+Eur116k identified 348 fine-mapped variants with posterior inclusion probability (PIP)>0.9, and MultiSuSiE applied to Afr36k+Lat36k+Eur36k identified 59% more PIP>0.9 variants than SuSiE applied to Eur109k; MultiSuSiE identified 29% more PIP>0.9 variants than SuSiEx, and MESuSiE was not included due to its high computational cost. We validated these findings through functional enrichment of fine-mapped variants and highlighted examples implicating biologically plausible fine-mapped variants.

DOI: 10.1038/s41588-025-02450-5

Source: https://www.nature.com/articles/s41588-025-02450-5