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Xuejuan Jiang, Darryl Nousome, Roberta McKean-Cowdin, Bruce Burkemper, Mina Torres, Rohit Varma; Association of Glaucoma-Susceptible Genes to Retinal Nerve Fiber Layer Thickness in Two Racial/Ethnic Populations in the US. Invest. Ophthalmol. Vis. Sci. 2018;59(9):778.
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Genome wide association studies (GWAS) of primary open angle glaucoma (POAG), intraocular pressure (IOP), and quantitative optic nerve head (ONH) parameters have identified multiple genetic loci. Thinning of the retinal nerve fiber layer (RNFL) is recognized as an important early sign of POAG. The aims of this study were to evaluate the association between the earlier reported POAG/IOP/ONH-related genes and RNFL thickness in normal eyes and assess if the genetic effects on RNFL manifest differently in different populations.
We identified 113 single nucleotide polymorphisms (SNPs) associated with POAG, IOP, and ONH parameters from the NHGRI-EBI GWAS Catalog. Genetic and phenotypic data were obtained from two population based-studies: the Los Angeles Latino Eye Study (LALES, n=2322) and the Chinese American Eye Study (CHES, n=1672). Participants were 49 years or older and free of POAG and other major ocular diseases. RNFL thickness was obtained from the right eye using Cirrus HD-OCT (Carl Zeiss Meditec Inc.). LALES participants were genotyped using either the llumina OmniExpress BeadChip or Illumina Hispanic/SOL BeadChip; CHES participants were genotyped using the Illumina HumanExome BeadChip. Linear regression was used to assess the relationship of SNPs with RNFL thickness assuming an additive model, with adjustments for population structure, age, sex, and signal strength.
In CHES, rs6598351 (near FAM169B) on chromosome 15, which has been associated with cup area, was associated with thinner average RNFL (MAF=0.25, β=-2.25 μm, p=0.0004). This SNP was not replicated in LALES (p=0.53, MAF=0.13). Additionally, in LALES, rs10998036 (near ATOH7) on chromosome 10, which has been associated with cup area and vertical cup-disc ratio, was associated with thinner average RNFL (MAF=0.31, β=-1.31 μm, p=0.0003). This association was not replicated in the CHES population (p=0.13, MAF=0.29).
Our findings support a role of glaucoma-susceptible genes on RNFL thickness in Mexican Americans and Chinese Americans with normal eyes. These SNPs exhibited relatively strong effect sizes, equivalent to the effect from 5-10 years of aging. There was also evidence for a modification of the genetic effects by race/ethnicity. Further investigations are needed to explore differences in linkage disequilibrium between the two populations to identify causative SNPs.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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