美国宾夕法尼亚大学Joan M. O’Brien团队近期取得重要工作进展，他们通过一项非洲血统个体的多队列全基因组关联研究，揭示出原发性开角型青光眼的风险位点。相关研究成果2024年1月18日在线发表于《细胞》杂志上。

据介绍，原发性开角型青光眼（POAG）是全球不可逆失明的主要原因，对非洲血统人的影响尤为严重。

研究人员对11275名非洲血统的个体（6003例；5272名对照）进行了POAG的全基因组关联研究（GWAS）。研究人员在全基因组意义上检测到46个与POAG相关的风险基因座。复制和GWAS后分析，包括功能信息的精细定位、多性状共定位和计算机验证，表明两个先前未描述的变体（rs1666698映射到DBF4P2；rs34957764映射到ROCK1P1）和一个先前相关的变体（rs11824032映射到ARHGEF12）可能是因果关系。

对于非洲血统的个体，他们的大型分析（非洲血统个体）数据中POAG的多基因风险评分（PRS）优于来自欧洲血统个体的更大GWAS汇总统计中的PRS。

总之，这项研究量化了非洲和非非洲血统人群之间，这种致盲疾病的遗传结构相似性和差异性。

附：英文原文

Title: A multi-cohort genome-wide association study in African ancestry individuals reveals risk loci for primary open-angle glaucoma

Author: Shefali S. Verma, Harini V. Gudiseva, Venkata R.M. Chavali, Rebecca J. Salowe, Yuki Bradford, Lindsay Guare, Anastasia Lucas, David W. Collins, Vrathasha Vrathasha, Rohini M. Nair, Sonika Rathi, Bingxin Zhao, Jie He, Roy Lee, Selam Zenebe-Gete, Anita S. Bowman, Caitlin P. McHugh, Michael C. Zody, Maxwell Pistilli, Naira Khachatryan, Ebenezer Daniel, Windell Murphy, Jeffrey Henderer, Tyler G. Kinzy, Sudha K. Iyengar, Neal S. Peachey, Kent D. Taylor, Xiuqing Guo, Yii-Der Ida Chen, Linda Zangwill, Christopher Girkin, Radha Ayyagari, Jeffrey Liebmann, Chimd M. Chuka-Okosa, Susan E. Williams, Stephen Akafo, Donald L. Budenz, Olusola O. Olawoye, Michele Ramsay, Adeyinka Ashaye, Onoja M. Akpa, Tin Aung, Janey L. Wiggs, Ahmara G. Ross, Qi N. Cui, Victoria Addis, Amanda Lehman, Eydie Miller-Ellis, Prithvi S. Sankar, Scott M. Williams, Gui-shuang Ying, Jessica Cooke Bailey, Jerome I. Rotter, Robert Weinreb, Chiea Chuen Khor, Michael A. Hauser, Marylyn D. Ritchie, Joan M. O’Brien

Issue&Volume: 2024/01/18

Abstract: Primary open-angle glaucoma (POAG), the leading cause of irreversible blindness worldwide, disproportionately affects individuals of African ancestry. We conducted a genome-wide association study (GWAS) for POAG in 11,275 individuals of African ancestry (6,003 cases; 5,272 controls). We detected 46 risk loci associated with POAG at genome-wide significance. Replication and post-GWAS analyses, including functionally informed fine-mapping, multiple trait co-localization, and in silico validation, implicated two previously undescribed variants (rs1666698 mapping to DBF4P2; rs34957764 mapping to ROCK1P1) and one previously associated variant (rs11824032 mapping to ARHGEF12) as likely causal. For individuals of African ancestry, a polygenic risk score (PRS) for POAG from our mega-analysis (African ancestry individuals) outperformed a PRS from summary statistics of a much larger GWAS derived from European ancestry individuals. This study quantifies the genetic architecture similarities and differences between African and non-African ancestry populations for this blinding disease.

DOI: 10.1016/j.cell.2023.12.006

Source: https://www.cell.com/cell/fulltext/S0092-8674(23)01338-7