Replication Analysis for Severe Diabetic Retinopathy

Purpose: The purpose of this study is to attempt to replicate the top single nucleotide polymorphism (SNP) associations from a previous genome-wide association study (GWAS) for the sight threatening complications of diabetic retinopathy in an independent cohort of diabetic subjects from the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR). Methods: This study included 469 type 1 diabetic, Caucasian subjects from WESDR. Cases (n=208) were defined by prior laser treatment for either proliferative diabetic retinopathy or diabetic macular edema. Controls (n=261) were all other subjects in the cohort. 389 SNPs were tested for association using the Illumina™ GoldenGate™ custom array. A retinopathy only sub-analysis was conducted in 437 subjects by removing those with end-stage renal disease. Evaluation for association between cases and controls was conducted by using Chi-square tests. A combined analysis incorporated the results from WESDR with the prior GWAS. Results: No associations were significant at a genome-wide level. The analysis did identify SNPs that can be pursued in future replication studies. The top association was at rs4865047, an intronic SNP, in the gene CEP135 (p-value 2.06x10-5). The top association from the sub-analysis was at rs1902491 (p-value 2.81x10-5), a SNP that sits upstream of the gene NPY2R. Conclusions: This study nominates several novel genetic loci that may be associated with severe diabetic retinopathy. In order to confirm these findings, replication and extension in additional cohorts will be necessary as susceptibility alleles for diabetic retinopathy appear to be of modest effect.