June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
G6P missense variant (rs1671152)and risk of primary open-angle glaucoma in African Americans from a biorepository linked to de-identified electronic medical records
Author Affiliations & Notes
  • Nicole Restrepo
    Center for Human Genetics Research, Vanderbilt University, Nashville, TN
  • Robert Goodloe
    Center for Human Genetics Research, Vanderbilt University, Nashville, TN
  • Eric Eager-Farber
    Center for Human Genetics Research, Vanderbilt University, Nashville, TN
  • Dana Crawford
    Department of Epidemiology & Biostatistics, Case Western Reserve University, Cleveland, OH
    Institute for Computational Biology, Case Western Reserve University, Cleveland, OH
  • Footnotes
    Commercial Relationships Nicole Restrepo, None; Robert Goodloe, None; Eric Eager-Farber, None; Dana Crawford, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 3681. doi:
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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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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract
 
Purpose
 

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.

 
Methods
 

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.

 
Results
 

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.

 
Conclusions
 

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.  

 
Table: Most significant associations in African American POAG association study
 
Table: Most significant associations in African American POAG association study

 
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