Genomic and Genetic Studies of Diabetic Retinopathy

糖尿病视网膜病变的基因组和遗传学研究

• 批准号: 8138404
• 负责人: MICHAEL A. GRASSI
• 金额: $ 19.29万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-15 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8138404
• 关键词: Genomic; Genetic; Studies; Diabetic; Retinopathy

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.

描述（由申请人提供）：十多年来，人们一直在进行广泛的研究，以了解糖尿病视网膜病变的遗传学。迄今为止，连锁和候选基因关联尚未得出明确的结果。 尽管存在这一挑战，但公认的是，遗传变异的鉴定，从而涉及糖尿病视网膜病变发病机制中涉及的基因和途径，提供了一种重要的机制，通过这种机制可以产生新的疗法并更好地预防这种疾病。随着人类基因组计划和HapMap计划的完成，以及Affytek 500 k SNP芯片等平台与生物信息学计算方法相结合的可用性，现在可以以具有成本效益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的，良好的表型特征的患者队列。为此，我们已经建立了合作，以分析两个大型人群的视网膜病变患者由于1型糖尿病。 具体目标1.在患有严重眼部疾病的1型糖尿病受试者和从糖尿病肾脏遗传学（GoKinD）研究中确定的对照组中进行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。具体目标2。在威斯康星州糖尿病视网膜病变流行病学研究（WESDR）中确定的患有严重眼病的1型糖尿病个体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。在显示与糖尿病视网膜病变相关的基因或区域中进行精细定位研究，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，对糖尿病视网膜病变遗传基础的理解应该导致预防这种糖尿病并发症的新治疗和方法。