Genome-wide analyses identify 68 new loci associated with intraocular pressure and improve risk prediction for primary open-angle glaucoma

Abstract

Glaucoma is the leading cause of irreversible blindness globally. 1 Despite its gravity, the disease is frequently undiagnosed in the community. 2 Raised intraocular pressure (IOP) is the most important risk factor for primary open-angle glaucoma (POAG). 3, 4 Here we present a meta-analysis of 139,555 European participants that identified 112 genomic loci associated with IOP, 68 of which are novel. These loci suggest a strong role for angiopoietin-receptor tyrosine kinase signaling, lipid metabolism, mitochondrial function and developmental processes underlying risk for elevated IOP. In addition, 48 of these loci were associated with glaucoma in an independent cohort, 14 of which at a Bonferroni-corrected threshold. Regression-based glaucoma prediction models had an area under Receiving Operator Characteristic curve (AUROC) of 0.76 in USA NEIGHBORHOOD study participants and 0.74 in independent glaucoma cases from UK Biobank. Genetic prediction models for POAG offer an opportunity to target screening and timely therapy to individuals most at risk.