A multi-cohort genome-wide association study in African ancestry individuals reveals risk loci for primary open-angle glaucoma
Publication information:
Verma S, Gudiseva H, Chavali V, Salowe R, Bradford Y, Guare L, Lucas A, Collins D, Vrathasha V, Nair R, Rathi S, Zhao B, He J, Lee R, Zenebe-Gete S, Bowman A, McHugh C, Zody M, Pistilli M, Khachatryan N, Daniel E, Murphy W, Henderer J, Kinzy T, Iyengar S, Peachey N, Taylor K, Guo X, Chen YDI, Zangwill L, Girkin C, Ayyagari R, Liebmann J, Chuka-Okosa C, Williams S, Akafo S, Budenz D, Olawoye O, Ramsay M, Ashaye A, Akpa O, Aung T, Wiggs J, Ross A, Cui Q, Addis V, Lehman A, Miller-Ellis E, Sankar P, Williams S, Ying GS, Bailey JC, Rotter J, Weinreb R, Khor CC, Hauser M, Ritchie M, O’Brien J. A multi-cohort genome-wide association study in African ancestry individuals reveals risk loci for primary open-angle glaucoma.
Cell. 2024;187(2):464–480.e10. PMID: 38242088
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.