Genomic and Genetic Studies of Diabetic Retinopathy

描述（由申请人提供）：为了了解糖尿病视网膜病变的遗传学，已经进行了十多年的广泛研究。到目前为止，联系和候选基因关联未能提供明确的结果。尽管存在这一挑战，但人们普遍认为，基因变异的鉴定，从而暗示了参与糖尿病视网膜病变发病机制的基因和途径，为产生新的治疗方法和更好地预防这种疾病提供了重要的机制。随着人类基因组计划和HapMap计划的完成，以及Affymetrix 500k SNP芯片等平台的可用性与生物信息学计算方法相结合，现在可以以经济有效的方式在基因组规模上识别遗传变异。主要的限制因素仍然是获得大量的、具有良好表型特征的患者队列。为此，我们建立了合作关系，分析了两组由1型糖尿病引起的视网膜病变患者。具体目标对患有严重眼病的1型糖尿病患者和来自糖尿病肾脏遗传学（GoKinD）研究的对照组的snp进行全基因组关联研究，以绘制与糖尿病视网膜病变相关的基因。具体目标2。在威斯康辛州糖尿病视网膜病变流行病学研究（WESDR）中确定的1型糖尿病严重眼病患者和对照组的单独队列中，证实这种全基因组关联的重要发现。具体目标3。开展与糖尿病视网膜病变相关的基因或区域的精细定位研究，并进行详细的基因型-表型分析。这项研究与公共卫生的相关性在于，了解糖尿病视网膜病变的遗传基础应该会导致新的治疗方法和预防这种糖尿病并发症的方法。

DESCRIPTION (provided by applicant): There have been extensive research efforts for more than a decade to understand the genetics of diabetic retinopathy. To date, linkage and candidate gene associations have failed to deliver definitive results. Despite this challenge, it is well accepted that the identification of genetic variants, thereby implicating genes and pathways involved in the pathogenesis of diabetic retinopathy, offers an important mechanism by which to generate new therapies and better prevent this disease. With the completion of the human genome project, as well as the HapMap project, and the availability of platforms like the Affymetrix 500k SNP chip combined with bioinformatic computational methods, it is now possible to identify genetic variants on a genome scale in a cost effective manner. The major limiting factor remains accessing large, well phenotypically characterized cohorts of patients. To this end, we have established collaborations to analyze two large populations of patients with retinopathy due to type 1 diabetes. Specific Aim 1. To carry out a genome wide association study of SNPs in a cohort of type 1 diabetic subjects with severe eye disease and controls ascertained from the Genetics of Kidneys in Diabetes (GoKinD) study to map genes associated with diabetic retinopathy. Specific Aim 2. To confirm significant findings from this genome wide association in a separate cohort of type 1 diabetic individuals with severe eye disease and controls ascertained from the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR). Specific Aim 3. To carry out fine-mapping studies in genes or regions showing association with diabetic retinopathy and perform detailed genotype-phenotype analyses. The relevance of this research to public health is that an understanding of the genetic basis of diabetic retinopathy should lead to novel treatments and methods for preventing this diabetic complication.