英国伦敦大学学院遗传学研究所Karoline Kuchenbaecker小组发现，重度抑郁症（MD）全基因组关联研究（GWAS）有助于发现基因座、精细绘图、确定基因优先级和因果推断。2024年1月4日出版的《自然-遗传学》杂志发表了这项成果。

研究人员开展了一项关于重度抑郁症的多人种GWAS研究，在之前报告数据的基础上增加了21个其它队列数据，包括88,316例重度抑郁症病例和902,757例对照。这项分析采用了一系列测量方法来定义MD，包括非洲人种（占有效样本量的36%）、东亚人种（26%）和南亚人种（6%）以及西班牙裔/拉美裔参与者（32%）。多人种GWAS发现了53个显著相关的新基因位点。

在欧洲人种中进行的样本基因组学分析可转移到其他人种群体的基因位点比预期的要少。精细绘图得益于样本的多样性。全转录组关联研究发现了205个明显相关的新基因。这些研究结果表明，对于MD来说，增加遗传研究中的人种多样性可能对发现核心基因和了解研究结果的可转移性尤为重要。

研究人员表示，大多数重度抑郁症的全基因组关联研究都是在欧洲人中进行。

附：英文原文

Title: Multi-ancestry genome-wide association study of major depression aids locus discovery, fine mapping, gene prioritization and causal inference

Author: Meng, Xiangrui, Navoly, Georgina, Giannakopoulou, Olga, Levey, Daniel F., Koller, Dora, Pathak, Gita A., Koen, Nastassja, Lin, Kuang, Adams, Mark J., Rentera, Miguel E., Feng, Yanzhe, Gaziano, J. Michael, Stein, Dan J., Zar, Heather J., Campbell, Megan L., van Heel, David A., Trivedi, Bhavi, Finer, Sarah, McQuillin, Andrew, Bass, Nick, Chundru, V. Kartik, Martin, Hilary C., Huang, Qin Qin, Valkovskaya, Maria, Chu, Chia-Yi, Kanjira, Susan, Kuo, Po-Hsiu, Chen, Hsi-Chung, Tsai, Shih-Jen, Liu, Yu-Li, Kendler, Kenneth S., Peterson, Roseann E., Cai, Na, Fang, Yu, Sen, Srijan, Scott, Laura J., Burmeister, Margit, Loos, Ruth J. F., Preuss, Michael H., Actkins, KyEra V., Davis, Lea K., Uddin, Monica, Wani, Agaz H., Wildman, Derek E., Aiello, Allison E., Ursano, Robert J., Kessler, Ronald C., Kanai, Masahiro, Okada, Yukinori, Sakaue, Saori, Rabinowitz, Jill A., Maher, Brion S., Uhl, George, Eaton, William, Cruz-Fuentes, Carlos S., Martinez-Levy, Gabriela A., Campos, Adrian I., Millwood, Iona Y., Chen, Zhengming, Li, Liming

Issue&Volume: 2024-01-04

Abstract: 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.

DOI: 10.1038/s41588-023-01596-4

Source: https://www.nature.com/articles/s41588-023-01596-4