Dataset Information

Glaucoma Risk Alleles in the Ocular Hypertension Treatment Study.

ABSTRACT: 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. We measured the relative risk for glaucoma that these factors contribute to participants in the Ocular Hypertension Treatment Study (OHTS). DESIGN:Comparative series. PARTICIPANTS:One thousand fifty-seven of 1636 participants (65%) of the OHTS were enrolled in this genetics ancillary study. METHODS:Samples of DNA 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 analyses of variance. The 2 largest subgroups, non-Hispanic whites (n = 752; 70.7%) and blacks (n = 249, 23.7%), also were analyzed separately. The probability of glaucoma developing over the course of the OHTS was compared between participants stratified for transmembrane and coiled-coil domains 1 (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 glaucoma developing than participants with no TMCO1 risk alleles. Moreover, the Cox proportional hazard analysis demonstrated that TMCO1 alleles increased relative risk comparable with that of some previously analyzed clinical measures (i.e., intraocular pressure). CONCLUSIONS:The size of the OHTS cohort and its composition of 2 large racial subgroups may limit its power to detect some glaucoma risk factors. However, TMCO1 genotype was found to increase the risk of glaucoma developing among non-Hispanic whites, the largest racial subgroup in the OHTS cohort, at a magnitude similar to clinical predictors of disease that long have been associated with glaucoma.

SUBMITTER: Scheetz TE

PROVIDER: S-EPMC5121091 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Glaucoma Risk Alleles in the Ocular Hypertension Treatment Study.

Scheetz Todd E TE Faga Ben B Ortega Lizette L Roos Ben R BR Gordon Mae O MO Kass Michael A MA Wang Kai K Fingert John H JH

Ophthalmology 20161001 12

<h4>Purpose</h4>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. We measured the relative risk for glaucoma that these factors contribute to participants in the Ocular Hypertension Treatment Study (OHTS).<h4>Design</h4>Comparative series.<h4>Participants</h4>One thousand fifty-seven of 1636 participants (65%) of the OHTS were enrolled in this genetics ancillary study.<h4>Me ...[more]

PMID: 27707548

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Project description:BACKGROUND:Both glaucoma and obstructive sleep apnea (OSA) are widespread diseases. OSA may presumably partly cause or worsen glaucoma, although the etiopathogenesis is unclear. Here we analyze for the first time the possible association between different glaucoma phenotypes and OSA. METHODS:110 patients (47 females, 63 males; median age 64.3?years, median BMI 26.62?kg/m2) with suspected glaucoma and without any prior diagnosis of OSA were prospectively studied by one-night home sleep apnea testing (HSAT), 101 of the patients were analyzed. HSAT parameters, like apnea hypopnea index (AHI) and oxygen desaturation index as well as opthalmological parameters like intraocular pressure (IOP) and mean defect depth (MD) were collected. Moreover, HSAT results were compared across four phenotypic groups: primary open angle glaucoma (POAG), low-tension-glaucoma (LTG), ocular hypertension (OH), and controls. RESULTS:There was no strong correlation between IOP or MD and AHI. BMI, age and gender did not differ between groups. Significant differences between POAG and LTG were found for all HSAT parameters. The AHI showed the most prominent group difference (Wilcoxon-Kruskal-Wallis rank sum test was highly significant with chi2?=?22, df?=?3 p?<?0.0001) with severely lower event rates in the LTG (9.45/h) compared to POAG (22.7/h) and controls (21.9/h; p?<?0.0001 and 0.02, respectively). Highly significant differences were found between the four groups regarding AHI (Chi2?=?22, df?=?3, p?<?0.0001) with significantly lower events per hour in the LTG compared to POAG (Hodges-Lehmann?=?-?13.8, 95% CI (-?18.6 - -?8.8; p?<?0.0001) and to controls (Hodges-Lehmann?=?12.1, 95% CI -19.9 - -?2.4; p?<?0.02). Severe and moderate OSA was more prevalent in POAG (69.8%) and OH (33.3%) than in LTG (9%). The effect of the glaucoma phenotype on the AHI was more prominent in females (p?=?0.0006) than in males (p?=?0.011). CONCLUSION:Although physical endpoints, such as MD and IOP, do not correlate with AHI, there was a strong correlation between the POAG and OH clinical glaucoma phenotypes and the AHI. Further studies should investigate the necessity to test routine screening for OSA by HSAT in patients with diagnosed POAG and OH. Besides, some characteristics of LTG differed widely from other glaucoma types and controls. LTG patients had a significantly lower rate of OSA compared to other glaucoma types and even controls. This might be due to a different pathogenesis of LTG. TRIAL REGISTRATION:Retrospectively registered at DRKS ( nr. S00021201 ) on April 9th 2020.

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Dataset Information

Glaucoma Risk Alleles in the Ocular Hypertension Treatment Study.

Publications

Glaucoma Risk Alleles in the Ocular Hypertension Treatment Study.

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