Glaucoma Risk Alleles in the Ocular Hypertension Treatment Study

Todd E Scheetz; Ben Faga; Lizette Ortega; Ben R Roos; Mae O Gordon; Michael A Kass; Kai Wang; John H Fingert

doi:10.1016/j.ophtha.2016.08.036

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Glaucoma Risk Alleles in the Ocular Hypertension Treatment Study

Journal article

Open access

Peer reviewed

Glaucoma Risk Alleles in the Ocular Hypertension Treatment Study

Todd E Scheetz, Ben Faga, Lizette Ortega, Ben R Roos, Mae O Gordon, Michael A Kass, Kai Wang and John H Fingert

Ophthalmology (Rochester, Minn.), Vol.123(12), pp.2527-2536

12/2016

DOI: 10.1016/j.ophtha.2016.08.036

PMCID: PMC5121091

PMID: 27707548

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http://doi.org/10.1016/j.ophtha.2016.08.036View

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Abstract

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). Comparative series. One thousand fifty-seven of 1636 participants (65%) of the OHTS were enrolled in this genetics ancillary study. 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. Association of POAG with known genetic factors. 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). 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.

European Continental Ancestry Group - genetics

Glaucoma, Open-Angle - genetics

Intraocular Pressure

Membrane Proteins - genetics

Gene Frequency

Humans

Middle Aged

Risk Factors

Genotype

Male

Genotyping Techniques

Glaucoma, Open-Angle - ethnology

Ocular Hypertension - genetics

Ocular Hypertension - therapy

Alleles

Tonometry, Ocular

Female

Polymorphism, Single Nucleotide

African Continental Ancestry Group - genetics

Cohort Studies

Details

Title: Subtitle: Glaucoma Risk Alleles in the Ocular Hypertension Treatment Study
Creators: Todd E Scheetz - Department Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa; Stephen A. Wynn Institute for Vision Research, University of Iowa, Iowa City, Iowa
Ben Faga - Department Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa; Stephen A. Wynn Institute for Vision Research, University of Iowa, Iowa City, Iowa
Lizette Ortega - Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa
Ben R Roos - Department Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa; Stephen A. Wynn Institute for Vision Research, University of Iowa, Iowa City, Iowa
Mae O Gordon - Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri
Michael A Kass - Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri
Kai Wang - Stephen A. Wynn Institute for Vision Research, University of Iowa, Iowa City, Iowa; Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa
John H Fingert - Department Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa; Stephen A. Wynn Institute for Vision Research, University of Iowa, Iowa City, Iowa. Electronic address: john-fingert@uiowa.edu
Resource Type: Journal article
Publication Details: Ophthalmology (Rochester, Minn.), Vol.123(12), pp.2527-2536
DOI: 10.1016/j.ophtha.2016.08.036
PMID: 27707548
PMCID: PMC5121091
NLM abbreviation: Ophthalmology
ISSN: 0161-6420
eISSN: 1549-4713
Publisher: United States
Grant note: R01 EY018825 / NEI NIH HHS UG1 EY025180 / NEI NIH HHS UG1 EY025181 / NEI NIH HHS UG1 EY025182 / NEI NIH HHS U10 EY009341 / NEI NIH HHS UG1 EY025183 / NEI NIH HHS R01 EY023512 / NEI NIH HHS U10 EY009307 / NEI NIH HHS
Language: English
Date published: 12/2016
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Electrical and Computer Engineering; Biostatistics; Ophthalmology and Visual Sciences
Record Identifier: 9983980056702771

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