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Gala Beykin, Michelle Grunin, Shira Levi, Batya Rinsky, Sarah Elbaz-Hayoun, Itay Chowers; Genome Wide Association Analysis for Sub Retinal Drusenoid Deposits. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1836. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Sub retinal drusenoid deposits (SRDD) are associated with age related macular degeneration (AMD). Limited data is available with respect to the genetic factors which are associated with this phenotype. We aimed to gain additional insight into the genetics of SRDD in AMD.
155 AMD patients, which were recruited at a single tertiary referral center, and that underwent genotyping using an exome-chip technique as part of the International AMD Genomic Consortium (IAMDGC) project, participated in this study. ~250K variants were genotyped and imputed to ~12 million variants by the IAMDGC. All 155 patients had available spectral domain optical coherence tomography (SD-OCT) and Infrared Reflectance (IR) images. SD-OCT sections and IR images were evaluated for the presence of SRDD by an observer who was masked to the genetic findings. After quality control and exclusion of variants with a minor allele frequency less than 0.05, 8,892,303 variants were analyzed via the bioinformatics software PLINK and epacts, including informative principle components, gender and age as covariates analysis. Logistic regression was performed in an unbiased approach, as well as a biased approach via regression and single variant testing, investigating 17,450 variants in the 34 loci known to be associated with AMD.
68 of the 155 patients had SRDD, seen both in OCT and IR [C1] in at least one eye. Variants were compared between AMD patients with or without SRDD via an unbiased analysis. Top hitting variants in this analysis approached a significance level of P≤0.00003; none of these significant variants was known to be associated with a risk locus for AMD. Via a biased approach on 34 known AMD loci, 11/34 loci had P<0.05 associated with SRDD in AMD compared with AMD without SRDD. The top association was found for SNPs in the CFH locus (P=0.0002, OR=0.31, 95% CI[0.17-0.58]), ABCA1 (P=0.0004, OR=5.4, 95% CI[2.11-14.01]), and in HTRA1 (P=0.001, OR=0.31, 95%CI[0.14-0.64]).
The presence of SRDD in AMD patients may be associated with novel genetic risk variants and/or with variants that were previously associated with the risk for having AMD. It remains to be seen if these loci are also associated with SRDD in other populations, and if they are related to the pathogenesis of this phenotype.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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