Genetics of Diabetic Retinopathy

描述（由申请人提供）：2型糖尿病持续威胁着个人、家庭和人群的健康，其发病率和死亡率主要归因于糖尿病的慢性并发症，如糖尿病视网膜病变。我们开发了一种独特的资源，能够识别导致糖尿病视网膜病变风险的遗传变异，已经识别了1100多个人，包括家庭和基于人群的亚群，我们有立体眼底照片和全基因组连锁数据。我们将很快获得其中相当一部分的全基因组关联数据（100,000+单核苷酸多态性- SNPs）。

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.