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Sudha K. Iyengar, Y-D Ida Chen, Emily Y. Chew, Robert P. Igo, Jr., Robert G. Nelson, Ronald P. Danis, Barry I. Freedman, John R. Sedor, Jerome I. Rotter, FIND Consortium; Identification of Novel Loci for Diabetic Retinopathy in European Americans: The Family Investigation of Nephropathy and Diabetes (FIND). Invest. Ophthalmol. Vis. Sci. 2011;52(14):4820.
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Diabetic Retinopathy (DR) is a common microvascular complication of type 1 and 2 diabetes mellitus (DM). It affects over 60% of diabetic individuals, and is a leading cause of visual impairment. DR ranges in severity from mild/moderate non-proliferative disease to proliferative disease, and is often accompanied by macular edema. In the hopes of gaining insights into DR susceptibility, we conducted a genome-wide association study (GWAS) in a European American sample with and without DR.
In FIND, participants had ophthalmological exams and stereoscopic seven-field retinal photos graded, and assessed according to the methods of the Early Treatment Diabetic Retinopathy Study Group (ETDRS). DNA from participants was genotyped using the Affymetrix 6.0 chip with ~ 950,000 markers, imputed to >2.4 million markers. Logistic regression was used to contrast cases with DR (N=105) versus controls (N = 627) who were disease free, adjusting for the effects of sex, study center, DM duration, and two principal components for population structure. Glycosylated hemoglobin was examined as a covariate, but not included because it was not significant.
The best p-value was on chromosome 20 at rs2425644 (Odds Ratio = 3.0; p = 1.2 x 10-7) within the serine incorporator 3 locus (SERINC3). SERINC3 is a transmembrane protein whose function has not been well characterized. In addition to SERINC3, several other loci with similar evidence on chromosomes 2, 3, 4, 5 and 14 were also observed. Genotyped and imputed markers in previously reported candidate genes such as EPO, VEGFA and its receptor KDR showed no association at p<0.05.
Our analysis has identified several novel loci for DR that may provide insights into DR etiology. We are pursuing replication of these results in additional samples in order to provide better support for these findings.
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