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

Cell. 2024 Jan 18;187(2):464-480.e10. doi: 10.1016/j.cell.2023.12.006.

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.

Keywords: African ancestry; Black; genetic risk factors; genome-wide association study; glaucoma; health disparities; neurodegeneration; ophthalmology; optic nerve; primary open-angle glaucoma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Black People / genetics
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study*
  • Glaucoma, Open-Angle* / genetics
  • Humans
  • Polymorphism, Single Nucleotide / genetics