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John H Fingert, Kai Wang, Ben Faga, Lizette Ortega, Mae O Gordon, Michael A Kass, Todd Scheetz; TMCO1 is associated with POAG in the Ocular Hypertension Treatment Study (OHTS). Invest. Ophthalmol. Vis. Sci. 2014;55(13):2145. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To determine if previously detected genetic risk factors are associated with developing POAG in participants in the Ocular Hypertension Treatment Study (OHTS).
OHTS participants had ocular hypertension and no clinical evidence of glaucoma at baseline. DNA and genotypes were available from 1057 OHTS participants. Of these, 209 developed POAG (cases) and 848 did not (controls) over 14 year follow-up. The allele frequencies of 14 previously discovered glaucoma risk alleles were compared between cases and controls using ANOVA. Secondary analyses examined allele frequency and POAG risk in self-reported non-Hispanic whites (70.7%) and self-reported blacks (23.7%). Kaplan-Meier and Cox proportional hazards analyses were used to determine if participants with POAG risk alleles were at higher risk of developing glaucoma those with no POAG risk alleles.
No association between known risk alleles and POAG were detected in the analysis of all 1057 participants in the OHTS. However, the allele frequencies of the risk factors (the TMCO1 locus) were statistically different between the non-Hispanic white cases and controls, p = 0.00028 (significant with multiple measures corrections for analysis of 14 genes). Kaplan-Meier analysis, showed that non-Hispanic white participants in the OHTS who have 1 or 2 TMCO1 risk alleles were at higher risk of developing POAG than those with no risk alleles (~10% more glaucoma at 14 years, log rank p = 0.0014).
While the size of the OHTS cohort may limit its power to detect some of the known glaucoma risk factors, our analysis demonstrates that the TMCO1 genotype contributes a detectable increase in the risk of developing glaucoma in the largest subgroup of the OHTS cohort (non-Hispanic whites).
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