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We report a genome-wide association study for open-angle glaucoma (OAG) blindness using a discovery cohort of 590 individuals with severe visual field loss (cases) and 3,956 controls. We identified associated loci at TMCO1 (rs4656461[G] odds ratio (OR) = 1.68, P = 6.1 × 10⁻¹⁰) and CDKN2B-AS1 (rs4977756[A] OR = 1.50, P = 4.7 × 10⁻⁹). We replicated these associations in an independent cohort of cases with advanced OAG (rs4656461 P = 0.010; rs4977756 P = 0.042) and two additional cohorts of less severe OAG (rs4656461 combined discovery and replication P = 6.00 × 10⁻¹⁴, OR = 1.51, 95% CI 1.35–1.68; rs4977756 combined P = 1.35 × 10⁻¹⁴, OR = 1.39, 95% CI 1.28–1.51). We show retinal expression of genes at both loci in human ocular tissues. We also show that CDKN2A and CDKN2B are upregulated in the retina of a rat model of glaucoma.