Genetics of Diabetic Retinopathy

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DESCRIPTION (provided by applicant): Type 2 diabetes continues to assault the health of individuals, families, and populations with the morbidity and mortality largely attributable to the chronic complications of diabetes, such as diabetic retinopathy. We have developed a singular resource to enable identification of genetic variation contributing to the risk of diabetic retinopathy having identified more than 1,100 individuals, encompassing both family and population-based subsets, for whom we have stereoscopic fundus photographs and genome-wide -linkage data. We will soon have first-pass genome-wide association data (100,000+ single nucleotide polymorphisms - SNPs) on a substantial proportion of these. Results from this study now establish a role for genes contributing to moderate to severe diabetic retinopathy and demonstrate increased morbidity associated with familial cases of type 2 diabetes. Our genome-wide linkage scan for diabetic retinopathy identifies 14 LOD score peaks that are candidates for follow-up; 9 of which appear to be retinopathy specific. These genetic and clinical resources will be used in this continuation to achieve: AIM 1: Identify genetic variation responsible for susceptibility to diabetic retinopathy based on follow-up of genome-wide linkage and association testing. AIM 2: Determine the ability of identified genetic variation to predict incident cases and progression of retinopathy among familial and representative type 2 diabetes cases. In Aim 2 we place genetic effects in the context of the epidemiology of diabetic retinopathy. The longitudinal data available in this study will allow determining whether those factors that predict incident retinopathy are the same as those that predict progression of retinopathy and the extent to which genetic factors are mediated through other known risk factors such as glycemic control. Such studies hold the promise that central mechanisms leading to retinopathy will be understood and subsequently exploited for moving retinopathy treatment from palliative to preventive.