Genetics of Diabetic Retinopathy

描述（由申请人提供）：2型糖尿病继续损害个人、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。我们已经开发了一种独特的资源，以识别导致糖尿病视网膜病变风险的遗传变异，已经确定了1,100多个个体，包括家庭和基于人群的子集，我们拥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大一部分的首过全基因组关联数据（10万多个单核苷酸多态性-SNP）。 这项研究的结果现在确立了基因在中重度糖尿病视网膜病变中的作用，并证明了与2型糖尿病家族性病例相关的发病率增加。我们对糖尿病视网膜病变的全基因组连锁扫描确定了14个LOD评分峰值，这些峰值是后续的候选者;其中9个似乎是视网膜病变特异性的。这些遗传和临床资源将用于本延续项目，以实现： 目标1：基于全基因组连锁和关联检测的随访，确定导致糖尿病视网膜病变易感性的遗传变异。 目标2：在家族性和代表性2型糖尿病病例中，确定已鉴定的遗传变异预测视网膜病变发病病例和进展的能力。 在目标2中，我们将遗传效应置于糖尿病视网膜病变流行病学的背景下。本研究中可用的纵向数据将允许确定预测视网膜病变事件的因素是否与预测视网膜病变进展的因素相同，以及遗传因素通过其他已知风险因素（如血糖控制）介导的程度。这些研究有望使人们了解导致视网膜病变的中枢机制，并随后将其用于将视网膜病变治疗从姑息性转为预防性。

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.