Whole-Genome Sequencing of Glaucoma Risk Variants in the Yoruba Population: Implications for Pharmacogenomics

Primary open-angle glaucoma in persons of African ancestry is characterised by younger age at onset, higher IOP at presentation, more aggressive progression, and poorer treatment response, suggesting population-specific genetic architectures that whole-genome sequencing can elucidate. This study conducts whole-genome sequencing to identify glaucoma risk variants in the Yoruba population and examines their pharmacogenomic implications for anti-glaucoma drug response. A case-control genome-wide association study design will be employed. Five hundred POAG cases and 500 matched healthy controls of confirmed Yoruba ancestry from Ibadan and Lagos will be recruited. Whole-genome sequencing at 30x coverage will be performed. Genome-wide association analysis, haplotype mapping, and polygenic risk score construction will be conducted. Pharmacogenomic analysis will specifically examine variants in CYP1A2, ADRB2, and prostanoid receptor genes known to influence prostaglandin analogue and beta-blocker response. Bioinformatics pipelines will include quality control filtering, imputation, and functional annotation using African-specific reference panels. Most published GWAS data for glaucoma are derived from European and Asian populations, with African populations dramatically underrepresented despite carrying the highest global glaucoma burden. Variants identified in non-African populations may not replicate in the Yoruba genome, and population-specific variants of large effect may have been missed entirely. This study generates the first Yoruba whole-genome dataset for glaucoma, contributing to the H3Africa consortium and the global diversity of ophthalmic genomics. Findings will have direct implications for personalised glaucoma treatment selection in Nigerian patients. Keywords: whole-genome sequencing, glaucoma, Yoruba population, pharmacogenomics, GWAS