Genetics of Diabetic Retinopathy

描述(申请人提供)：2型糖尿病继续危害个人、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来识别导致糖尿病视网膜病变风险的基因变异，已经确定了1100多个个体，包括基于家庭和基于人群的亚组，我们有他们的立体眼底照片和全基因组联系数据。我们很快就会有关于其中相当大一部分的首个全基因组关联数据(100,000+单核苷酸多态-SNP)。 这项研究的结果现在确定了导致中到重度糖尿病视网膜病变的基因的作用，并证明了与2型糖尿病家族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，这些峰是后续研究的候选对象；其中9个似乎是视网膜病变特有的。这些遗传和临床资源将在这次延续中用于实现以下目标： 目的1：基于全基因组连锁和关联测试的随访，确定与糖尿病视网膜病变易感性有关的基因变异。 目的2：在家族性和代表性的2型糖尿病患者中，确定已识别的基因变异预测视网膜病变发病和进展的能力。 在目标2中，我们将遗传效应放在糖尿病视网膜病变的流行病学背景下。这项研究中可获得的纵向数据将有助于确定预测视网膜病变发生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)调节的程度。这些研究认为，视网膜病变的中枢机制将被理解，并随后被用于将视网膜病变的治疗从姑息性治疗转向预防性治疗。

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.