Biogen, Cambridge, MA 02142, USA; Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli 35053, Taiwan.
Cell Genom. 2023 Nov 16;3(12):100436. doi: 10.1016/j.xgen.2023.100436. eCollection 2023 Dec 13.
Genome-wide association studies (GWASs) have identified tens of thousands of genetic loci associated with human complex traits. However, the majority of GWASs were conducted in individuals of European ancestries. Failure to capture global genetic diversity has limited genomic discovery and has impeded equitable delivery of genomic knowledge to diverse populations. Here we report findings from 102,900 individuals across 36 human quantitative traits in the Taiwan Biobank (TWB), a major biobank effort that broadens the population diversity of genetic studies in East Asia. We identified 968 novel genetic loci, pinpointed novel causal variants through statistical fine-mapping, compared the genetic architecture across TWB, Biobank Japan, and UK Biobank, and evaluated the utility of cross-phenotype, cross-population polygenic risk scores in disease risk prediction. These results demonstrated the potential to advance discovery through diversifying GWAS populations and provided insights into the common genetic basis of human complex traits in East Asia.
全基因组关联研究（GWAS）已经确定了数以万计与人类复杂特征相关的遗传位点。然而，大多数 GWAS 都是在欧洲血统的个体中进行的。未能捕捉到全球遗传多样性限制了基因组的发现，并阻碍了基因组知识在不同人群中的公平传播。在这里，我们报告了来自台湾生物银行（TWB）的 102900 个人的 36 个人类定量特征的研究结果，这是一项重大的生物银行努力，拓宽了东亚遗传研究的人群多样性。我们确定了 968 个新的遗传位点，通过统计精细映射确定了新的因果变异，比较了 TWB、日本生物银行和英国生物银行的遗传结构，并评估了跨表型、跨人群多基因风险评分在疾病风险预测中的应用。这些结果表明，通过多样化 GWAS 人群来推进发现具有潜力，并为东亚人类复杂特征的共同遗传基础提供了见解。
