马萨诸塞州总医院Alicia R. Martin小组宣布他们的最新研究提出了泛英生物库全基因组关联分析增强了发现和解决祖先富集效应。2025年9月18日，国际知名学术期刊《自然—遗传学》发表了这一成果。

在这里，该课题组生成了混合模型关联和跨遗传祖先群体的荟萃分析，包括比以前更大比例的英国生物银行，以产生免费提供的7266个特征的汇总统计数据。该课题组研究人员建立了一个质量控制和分析框架通知遗传结构。总的来说，研究小组确定了14676个显著位点（P < 5 × 10^-8)在荟萃分析中没有单独在EUR遗传祖先组中发现，包括新的关联，例如CAMK2D和甘油三酯之间。研究团队还强调了来自祖先富集变异的关联，包括G6PD中已知的与几种生物标志物性状相关的多效错义变异。该研究组将这些结果与常见问题一起公开发布，这些问题描述了结果解释的注意事项，增强了解释不同人群风险变异的可用资源。

研究人员表示，大型生物库，如英国生物库（UKB），通过全基因组关联研究，阐明了复杂性状的遗传病因，从而实现了大量的现象。然而，来自不同遗传祖先群体的人往往被排除在关联分析之外，因为担心人口结构会引入假阳性关联。

附：英文原文

Title: Pan-UK Biobank genome-wide association analyses enhance discovery and resolution of ancestry-enriched effects

Author: Karczewski, Konrad J., Gupta, Rahul, Kanai, Masahiro, Lu, Wenhan, Tsuo, Kristin, Wang, Ying, Walters, Raymond K., Turley, Patrick, Callier, Shawneequa, Shah, Nirav N., Baya, Nikolas, Palmer, Duncan S., Goldstein, Jacqueline I., Sarma, Gopal, Solomonson, Matthew, Cheng, Nathan, Bryant, Sam, Churchhouse, Claire, Cusick, Caroline M., Poterba, Timothy, Compitello, John, King, Daniel, Zhou, Wei, Seed, Cotton, Finucane, Hilary K., Daly, Mark J., Neale, Benjamin M., Atkinson, Elizabeth G., Martin, Alicia R.

Issue&Volume: 2025-09-18

Abstract: Large biobanks, such as the UK Biobank (UKB), enable massive phenome by genome-wide association studies that elucidate genetic etiology of complex traits. However, people from diverse genetic ancestry groups are often excluded from association analyses due to concerns about population structure introducing false positive associations. Here we generate mixed model associations and meta-analyses across genetic ancestry groups, inclusive of a larger fraction of the UK Biobank than previous efforts, to produce freely available summary statistics for 7,266 traits. We build a quality control and analysis framework informed by genetic architecture. Overall, we identify 14,676 significant loci (P<5×108) in the meta-analysis that were not found in the EUR genetic ancestry group alone, including new associations, for example between CAMK2D and triglycerides. We also highlight associations from ancestry-enriched variation, including a known pleiotropic missense variant in G6PD associated with several biomarker traits. We release these results publicly alongside frequently asked questions that describe caveats for interpretation of results, enhancing available resources for interpretation of risk variants across diverse populations.

DOI: 10.1038/s41588-025-02335-7

Source: https://www.nature.com/articles/s41588-025-02335-7