July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Family-Based Association Tests of Myopia reveal a potentially hidden association signal upstream of two GABA receptor genes
Author Affiliations & Notes
  • Candace Middlebrooks
    National Human Genome Research Inst, National Institutes of Health, Baltimore, Maryland, United States
  • Claire L. Simpson
    Department of Genetics, Genomics and Informatics, Univ of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Anthony Musolf
    National Human Genome Research Inst, National Institutes of Health, Baltimore, Maryland, United States
  • Laura Portas
    CNR, Institute of Population Genetics, Li Punti, Sassari, Italy
  • Federico Murgia
    CNR, Institute of Population Genetics, Li Punti, Sassari, Italy
  • Elise B. Ciner
    Salus University, Elkins, Park, Pennsylvania, United States
  • Dwight Stambolian
    Ophthalmology-Stellar Chance Lab, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Joan E Bailey-Wilson
    National Human Genome Research Inst, National Institutes of Health, Baltimore, Maryland, United States
  • Footnotes
    Commercial Relationships   Candace Middlebrooks, None; Claire Simpson, None; Anthony Musolf, None; Laura Portas, None; Federico Murgia, None; Elise Ciner, None; Dwight Stambolian, None; Joan Bailey-Wilson, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 702. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Candace Middlebrooks, Claire L. Simpson, Anthony Musolf, Laura Portas, Federico Murgia, Elise B. Ciner, Dwight Stambolian, Joan E Bailey-Wilson; Family-Based Association Tests of Myopia reveal a potentially hidden association signal upstream of two GABA receptor genes. Invest. Ophthalmol. Vis. Sci. 2018;59(9):702.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Myopia is an eye condition in which distant objects appear out of focus. Within recent years, the incidence and prevalence of Myopia have increased in most populations. While population based association studies are well-powered for the identification of common variants, they are not well suited for the identification of rare variants. We sought to identify both population-specific and general rare variants that increase risk for Myopia.

Methods : We performed a family-based association test (FBAT) of Myopia using Exome Chip genotyping (Illumina Human Exome v1.1 array plus 24,263 custom SNPs) in five family cohorts for a total of 1718 subjects in 261 multiplex Myopia families. Individuals in the families were defined as myopic if their average refractive error was <= -1 Diopter (D) and were considered unaffected if it was > 0.0 D. After quality control, there were ~127,000 polymorphic SNPs. We used FBAT software to test for associations at the variant and gene-level.

Results : FBAT analysis resulted in a significant association in a region upstream of two gamma-Aminobutryric Acid (GABA) receptor genes (GABRA6; GABRB2). GABA is a neurotransmitter that has been implicated in refractive development. The associated SNP, rs1373602, is not found in the Genotype-Tissue Expression (GTEx) project, but a nearby SNP, rs62381591, has been identified as an expression quantitative trait locus for the GABRA6 gene. As the significant variant is common, we wondered why the larger, population-based association studies of Myopia have not detected an association in this region. We found that this variant is not in high linkage disequilibrium with any other variants in our dataset (highest r2 was ~0.002) and is indicated as triallelic in the 1000 genomes dataset (although it was biallelic in our dataset).

Conclusions : Potentially, this region harbors a missed signal that is tagged by a variant which is filtered out before GWAS analysis due to it being triallelic and not tagged by any other variant in the region. Additionally, using a family-based study may have increased our power to detect the effect. We plan to follow-up this analysis by collaborating with groups that have performed genome-wide genotyping studies of Myopia to determine if this signal was missed due to the aforementioned reasons.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×