July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Exome-chip Association Study of Refractive Error in U.S. Caucasians
Author Affiliations & Notes
  • Deyana Lewis
    National Human Genome Research Institute, Owings Mills, Maryland, United States
  • Ishika Jain
    National Human Genome Research Institute, Owings Mills, Maryland, United States
  • Theresa Alexander
    National Human Genome Research Institute, Owings Mills, Maryland, United States
    National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland, United States
  • Anthony Musolf
    National Human Genome Research Institute, Owings Mills, Maryland, United States
  • Dwight Stambolian
    Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, California, United States
  • Joan E Bailey-Wilson
    National Human Genome Research Institute, Owings Mills, Maryland, United States
  • Footnotes
    Commercial Relationships   Deyana Lewis, None; Ishika Jain, None; Theresa Alexander, None; Anthony Musolf, None; Dwight Stambolian, None; Joan Bailey-Wilson, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 5860. doi:
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      Deyana Lewis, Ishika Jain, Theresa Alexander, Anthony Musolf, Dwight Stambolian, Joan E Bailey-Wilson; Exome-chip Association Study of Refractive Error in U.S. Caucasians. Invest. Ophthalmol. Vis. Sci. 2019;60(9):5860.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Consequently, great efforts have been undertaken to identify and understand the mechanisms underlying the development and progression of myopia, a refractive error condition where light fails to properly focus on the retina of the eye, causing blurry vision. Genome-wide association studies and linkage studies have identified loci influencing the risk of developing myopia but, few causal variants have been identified with the majority of them being common (minor allele frequency > 0.05). Therefore, this study aims to determine whether rare variants may account for some of the variation of refractive error.

Methods : 1562 Caucasians who were controls with refractive error measurements from the Age-Related Eye Disease Study (AREDS) were genotyped using the Illumina Human Exome v1.1 array plus at CIDR. Myopia is defined in terms of refractive error (RE), a quantitative trait measured in Diopters (D), such that individuals with RE of -0.5D or more negative generally require glasses to correct their vision. Quality control was performed using PLINK. After quality control, over 100,000 rare variants were analyzed using EMMAX in the EPACTS software package to perform gene-based association tests, Combined Multivariate and Collapsing (CMC) and Variable Threshold (VT).

Results : EMMAX single-marker analysis identified 18 rare variants that were genome wide significant (p< 5 x 10-8). Interesting candidate variants were found in genes NIPSNAP2, TSSK3 and IDH1. Gene-based analyses for both tests yielded the most significant association for SH3GLB2. This gene’s function related to Myopia is unknown. IDH1 yielded a p-value of 6.4x10-4 within the top 5,000 variants for both CMC and VT gene-based tests. One study identified a role for IDH1 in bovine eyes, where the enzyme protein fulfills the criteria for a corneal epithelial crystallin, which may be involved in maintaining corneal epithelial transparency. We are extending our analyses by performing a joint mega-analyses across major ethnic groups by combining data from other studies in the CREAM consortium.

Conclusions : We identified 18 rare variants that were genome-wide significant for myopia in Caucasians. However, these novel specific signals still need to be replicated. We are extending our analyses by performing a joint mega-analyses across major ethnic groups by combining data from other studies in the CREAM consortium.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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