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Nicole Restrepo, Robert Goodloe, Eric Eager-Farber, Dana Crawford; G6P missense variant (rs1671152)and risk of primary open-angle glaucoma in African Americans from a biorepository linked to de-identified electronic medical records. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3681.
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Primary open-angle glaucoma (POAG) is the second leading cause of permanent vision loss and blindness in the U.S. Genome-wide and candidate gene association studies have identified loci associated with POAG risk in European-descent and Japanese populations. African Americans are ~15 times as likely to develop permanent vision impairment from glaucoma vs. European Americans, yet few studies have been performed in this population. We as the Epidemiologic Architecture for Genes Linked to Environment (EAGLE) study accessed the Vanderbilt University Medical Center’s BioVU, a DNA repository linked to de-identified electronic medical records, to identify cases and controls of POAG among African Americans to perform a genetic association study.
Using a combination of International Classification of Diseases diagnostic codes, Current Procedural Terminology billing codes, and manual review of clinical records, we identified 114 African American POAG cases and 1341 controls. Cases/controls were genotyped on the Metabochip, an Illumina genotype array targeting ~200,000 SNPs chosen with an emphasis on metabolic diseases and traits. After quality control, ~116k SNPs were included in analyses. We performed single SNP tests of association for common variants (MAF>0.05) using logistic regression in PLINK assuming an additive genetic model adjusted for age, sex, and first three principal components.
None of the tests of association passed a strict Bonferroni correction (p<4.3x10-7). The five most significant associations are shown in the table.
Our study did not detect a strong association for POAG risk in African Americans on the Metabochip. Small sample sizes and lack of genome wide coverage are major limitations in this study. Of interest for future studies is rs1671152 (OR=1.87; p =4.53x10-5), a known missense variant in the glycoprotein VI (GP6) gene. GP6, a collagen receptor, is involved in platelet aggregation but is expressed in the eye and brain. Potential implications may include scleral collagen organization and integrity of the blood-retinal barrier in glaucoma susceptibility.
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