Genomic and Genetic Studies of Diabetic Retinopathy

描述（由申请人提供）：十多年来，为了了解糖尿病视网膜病变的遗传学，人们进行了大量的研究工作。迄今为止，连锁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，遗传变异的鉴定，从而暗示参与糖尿病视网膜病变发病机制的基因和途径，为产生新疗法和更好地预防这种疾病提供了重要机制。随着人类基因组计划和 HapMap 计划的完成，以及 Affymetrix 500k SNP 芯片等平台与生物信息学计算方法的结合，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。主要限制因素仍然是接触大量具有良好表型特征的患者群体。为此，我们建立了合作关系，对两大 1 型糖尿病视网膜病变患者群体进行分析。 具体目标 1. 在患有严重眼病的 1 型糖尿病受试者和通过糖尿病肾脏遗传学 (GoKinD) 研究确定的对照人群中进行 SNP 的全基因组关联研究，以绘制与糖尿病视网膜病变相关的基因图谱。具体目标 2. 在患有严重眼病的 1 型糖尿病个体和威斯康星州糖尿病视网膜病变流行病学研究 (WESDR) 确定的对照组的单独队列中，证实这种全基因组关联的显着发现。 具体目标 3. 对与糖尿病视网膜病变相关的基因或区域进行精细定位研究，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带来预防这种糖尿病并发症的新疗法和方法。

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.