Division of Psychiatry, UCL, London, UK.
UCL Genetics Institute, UCL, London, UK.
Nat Genet. 2024 Feb;56(2):222-233. doi: 10.1038/s41588-023-01596-4. Epub 2024 Jan 4.
Most genome-wide association studies (GWAS) of major depression (MD) have been conducted in samples of European ancestry. Here we report a multi-ancestry GWAS of MD, adding data from 21 cohorts with 88,316 MD cases and 902,757 controls to previously reported data. This analysis used a range of measures to define MD and included samples of African (36% of effective sample size), East Asian (26%) and South Asian (6%) ancestry and Hispanic/Latin American participants (32%). The multi-ancestry GWAS identified 53 significantly associated novel loci. For loci from GWAS in European ancestry samples, fewer than expected were transferable to other ancestry groups. Fine mapping benefited from additional sample diversity. A transcriptome-wide association study identified 205 significantly associated novel genes. These findings suggest that, for MD, increasing ancestral and global diversity in genetic studies may be particularly important to ensure discovery of core genes and inform about transferability of findings.
大多数重度抑郁症（MD）的全基因组关联研究（GWAS）都是在欧洲血统的样本中进行的。在这里，我们报告了一项多血统的 MD GWAS，将来自 21 个队列的 88316 例 MD 病例和 902757 例对照的数据添加到之前报告的数据中。这项分析使用了一系列措施来定义 MD，包括非洲血统（有效样本量的 36%）、东亚血统（26%）和南亚血统（6%）以及西班牙裔/拉丁裔参与者（32%）的样本。多血统的 GWAS 确定了 53 个与 MD 显著相关的新位点。对于来自欧洲血统样本的 GWAS 中的位点，能够转移到其他血统群体的位点数量低于预期。精细映射得益于更多的样本多样性。全转录组关联研究确定了 205 个与 MD 显著相关的新基因。这些发现表明，对于 MD 而言，在遗传研究中增加祖先和全球多样性可能特别重要，以确保核心基因的发现，并提供有关研究结果可转移性的信息。
