Primary open-angle glaucoma (POAG) is a common disease requiring early diagnosis and treatment to avoid asymptomatic visual field loss and eventual blindness. LMX1B mutations cause dominantly-inherited Nail-Patella syndrome in which approximately 33% of patients develop glaucoma. This study investigated the wider role of LMX1B in POAG. The contribution of variation at the LMXIB locus to risk of glaucoma was investigated in a case-control genetic association study in 272 patients with high-tension glaucoma (HTG), 37 patients with normal-tension glaucoma (NTG), 58 patients with ocular hypertension (OHT), and 276 controls. Significant SNP associations were found for each patient group: rs7859156 was associated with HTG (P=0.0015; odds ratio [OR], 0.64) and OHT (P=0.0482; OR, 0.59); rs7854658 was associated with NTG (P=0.0041; OR, 0.30). A protective ATG haplotype (including rs7859156) was less prevalent in patients with raised intraocular pressure (22.7% in combined HTG+OHT group vs. 31.7% in controls; P=0.0005), and in patients with glaucoma (22.9% in combined HTG+NTG group vs. 31.7% in controls; P=0.0008). ATG carriers in these combined groups had a decreased risk of developing glaucoma (OR, 0.72 and OR, 0.73, respectively). A GCAGAC haplotype (including rs7854658) was also less prevalent in glaucoma patients (16.5% vs. 24.7%; P=0.0005) and carriers had a decreased risk of developing glaucoma (OR, 0.70). LMX1B haplotypes influence susceptibility to glaucoma in the general population, suggesting altered LMX1B function predisposes to glaucomatous damage and that this role may be independent of raised intraocular pressure.