Purpose Primary open angle glaucoma (POAG) is a major cause of blindness and visual disability. Several genetic risk factors for POAG and optic nerve features have been identified. Here we measure the relative risk for glaucoma these factors contribute to participants in the Ocular Hypertension Treatment Study (OHTS). Design Comparative Series Participants 1057 (65%) of the 1636 participants of the OHTS were enrolled in this genetics ancillary study. Methods DNA samples were available from 1057 OHTS participants. Of these, 209 developed POAG (cases) and 848 did not develop glaucoma (controls) between 1994 and 2009. The frequencies of 13 risk alleles previously associated with POAG or with optic disc features in other cohorts were compared between POAG cases and controls in the OHTS cohort using ANOVA. The two largest subgroups non-Hispanic whites (n = 752; 70.7%) and blacks (n = 249, 23.7%) were also analyzed separately. The probability of developing glaucoma over the course of the OHTS was compared between participants stratified for TMCO1 risk alleles using Kaplan-Meier and Cox proportional hazards analyses. Main Outcome Measures Association of POAG with known genetic factors. Results No association was detected between the known POAG risk alleles when the OHTS cohort was examined as a whole. However, in the subgroup of non-Hispanic whites, allele frequencies at the TMCO1 locus were statistically different between cases and controls (p = 0.00028). By 13 years, non-Hispanic white participants with TMCO1 risk alleles had a 12% higher cumulative frequency of developing glaucoma than participants with no TMCO1 risk alleles. Moreover, the Cox proportional hazard analysis demonstrated that TMCO1 alleles increase relative risk comparable to that of some previously analyzed clinical measures (i.e. intraocular pressure). Conclusions The size of the OHTS cohort and its composition of two large racial subgroups may limit its power to detect some glaucoma risk factors. However, TMCO1 genotype was found to increase risk for developing glaucoma among non-Hispanic whites, the largest racial subgroup in the OHTS cohort, at a magnitude similar to clinical predictors of disease that have long been associated with glaucoma.

No abstract