美国密歇根大学 Cristen J. Willer 和美国斯坦福大学 Themistocles L. Assimes 合作，并联合众多单位共同探讨了遗传多样性在血脂全基因组关联研究（GWAS）中的作用，这一研究成果于2021年12月9日在线发表在《自然》杂志上。

在这里，研究人员对大约 165 万人的血脂水平进行了多血统、全基因组遗传的系统分析，其中包括35万非欧洲血统的人。研究人员量化了研究非欧洲祖先的数据，并提供证据支持扩大招募额外血统，即使样本量相对较小。研究人员发现，只有增加血统多样性而不是研究更多的欧洲血统的个体，才能实质性的提高绘制功能变异图谱的精细度和改善多基因预测的可移接性 (评估了大约29.5万人，来自7个血统)。在发现的基因座和遗传特异性变异的数量上也得到了一定的增加。随着 GWAS 将侧重点从基因和基础生物学的识别扩展到预防和精准医学的遗传变异上，研究人员预期，参与者多样性的增加将导致多基因评价在临床实践中更准确、更公平的应用。

据了解，由于不同的饮食模式和药物使用，血脂水平升高是心血管疾病的遗传危险因素，在世界范围内患病率各不相同。尽管在预防和治疗方面取得了进展，特别是通过降低低密度脂蛋白胆固醇水平，但是心脏病仍然是目前全世界死亡的主要原因。血脂水平的全基因组关联研究 (GWAS) 为心血管疾病带来了重要的生物学和临床见解，以及新的药物靶点。然而，在此之前，大多数 GWAS 是在欧洲血统人群中进行的，并且可能遗漏了导致其他血统群体血脂水平变化的遗传变异因素，包括等位基因频率、效应大小和连锁不平衡模式的差异。

附：英文原文

Title: The power of genetic diversity in genome-wide association studies of lipids

Author: Graham, Sarah E., Clarke, Shoa L., Wu, Kuan-Han H., Kanoni, Stavroula, Zajac, Greg J. M., Ramdas, Shweta, Surakka, Ida, Ntalla, Ioanna, Vedantam, Sailaja, Winkler, Thomas W., Locke, Adam E., Marouli, Eirini, Hwang, Mi Yeong, Han, Sohee, Narita, Akira, Choudhury, Ananyo, Bentley, Amy R., Ekoru, Kenneth, Verma, Anurag, Trivedi, Bhavi, Martin, Hilary C., Hunt, Karen A., Hui, Qin, Klarin, Derek, Zhu, Xiang, Thorleifsson, Gudmar, Helgadottir, Anna, Gudbjartsson, Daniel F., Holm, Hilma, Olafsson, Isleifur, Akiyama, Masato, Sakaue, Saori, Terao, Chikashi, Kanai, Masahiro, Zhou, Wei, Brumpton, Ben M., Rasheed, Humaira, Ruotsalainen, Sanni E., Havulinna, Aki S., Veturi, Yogasudha, Feng, QiPing, Rosenthal, Elisabeth A., Lingren, Todd, Pacheco, Jennifer Allen, Pendergrass, Sarah A., Haessler, Jeffrey, Giulianini, Franco, Bradford, Yuki, Miller, Jason E., Campbell, Archie, Lin, Kuang, Millwood, Iona Y., Hindy, George, Rasheed, Asif, Faul, Jessica D., Zhao, Wei, Weir, David R., Turman, Constance, Huang, Hongyan, Graff, Mariaelisa, Mahajan, Anubha, Brown, Michael R., Zhang, Weihua

Issue&Volume: 2021-12-09

Abstract: Increased blood lipid levels are heritable risk factors of cardiovascular disease with varied prevalence worldwide owing to different dietary patterns and medication use1. Despite advances in prevention and treatment, in particular through reducing low-density lipoprotein cholesterol levels2, heart disease remains the leading cause of death worldwide3. Genome-wideassociation studies (GWAS) of blood lipid levels have led to important biological and clinical insights, as well as new drug targets, for cardiovascular disease. However, most previous GWAS4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23 have been conducted in European ancestry populations and may have missed genetic variants that contribute to lipid-level variation in other ancestry groups. These include differences in allele frequencies, effect sizes and linkage-disequilibrium patterns24. Here we conduct a multi-ancestry, genome-wide genetic discovery meta-analysis of lipid levels in approximately 1.65million individuals, including 350,000 of non-European ancestries. We quantify the gain in studying non-European ancestries and provide evidence to support the expansion of recruitment of additional ancestries, even with relatively small sample sizes. We find that increasing diversity rather than studying additional individuals of European ancestry results in substantial improvements in fine-mapping functional variants and portability of polygenic prediction (evaluated in approximately295,000 individuals from 7ancestry groupings). Modest gains in the number of discovered loci and ancestry-specific variants were also achieved. As GWAS expand emphasis beyond the identification of genes and fundamental biology towards the use of genetic variants for preventive and precision medicine25, we anticipate that increased diversity of participants will lead to more accurate and equitable26 application of polygenic scores in clinical practice.

DOI: 10.1038/s41586-021-04064-3

Source: https://www.nature.com/articles/s41586-021-04064-3