Genetic Studies of Diabetic Complications

糖尿病并发症的遗传学研究

• 批准号: 7224586
• 负责人: Nancy J Cox
• 金额: $ 48.16万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-30 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7224586
• 关键词: acute renal failure; clinical research; diabetes mellitus genetics; diabetic nephropathy; family genetics; functional /structural genomics; genetic mapping; genetic polymorphism; genetic susceptibility; genotype; human data; information systems; interdisciplinary collaboration; medical complication; microarray technology; phenotype

DESCRIPTION (provided by applicant): We, as a society, have made tremendous investments in developing the scientific infrastructure to enable breakthrough discoveries on the primary biological risk factors for common disorders, such as diabetes, and its common complications, including kidney failure. These disorders account for a disproportionate and growing share of public health care expenditures. While it is clear that the relationships between genetic variation and these common disease phenotypes are complex, there is good preliminary evidence that identifying genetic risk factors for common disorders will improve understanding of their etiology and pathogenesis, leading to more specific and effective therapies. Moreover, since virtually all common disease arises as a consequence of the actions and interactions of both genetic and non-genetic risk factors, the identification of genetic risk factors should allow design of epidemiological studies to identify more specific non-genetic risk factors that might be cost-effective targets for prevention of disease. The recent development of high-throughput platforms for very large-scale SNP genotyping makes genome-wide association (GWA) mapping a viable additional tool in the effort to identify genetic risk factors for diabetic complications including kidney failure and related phenotypes. Effective use of this tool, however, requires both investment in methods of genetic analysis and a keen understanding of the phenotypes. We have thus put together a multi-disciplinary team including statistical geneticists, molecular geneticists, and experts on kidney function and failure and propose to apply a variety of approaches for genome-wide association studies on kidney failure and related quantitative phenotypes using the GoKinD samples. Specifically, we propose to 1) genotype all probands and parents in the GoKinD collection (2,807 individuals) using the Illumina HapMap 300 beadchip platform; 2) conduct both standard and novel genetic analyses of the data to map genes associated with diabetic nephropathy and related phenotypes; 3) verify genotyping and carry out fine-mapping studies in genes or regions showing association with diabetic nephropathy, related quantitative phenotypes, and other measures of diabetic complications measured in the GoKinD samples. Identification of the genes and the specific genetic variants that contribute to the development of diabetic nephropathy will lead to new approaches for preventing and treating this common long-term complication of diabetes.

描述（由申请人提供）： 作为一个社会，我们在开发科学基础设施方面做出了巨大的投资，以使人们对常见疾病的主要生物学风险因素（例如糖尿病及其常见并发症，包括肾脏衰竭）的突破性进行突破。这些疾病解释了公共卫生保健支出的不成比例和不断增长的份额。虽然很明显，遗传变异与这些常见疾病表型之间的关系很复杂，但有良好的初步证据表明，鉴定常见疾病的遗传危险因素将改善对其病因和发病机理的理解，从而导致更具体而有效的疗法。此外，由于几乎所有常见的疾病都是由于遗传和非遗传危险因素的作用和相互作用而产生的，因此遗传危险因素的鉴定应允许设计流行病学研究，以确定可能是预防疾病的更具体的非遗传危险因素。最近开发了针对非常大规模SNP基因分型的高通量平台的开发，使整个基因组关联（GWA）绘制了可行的额外工具，以识别糖尿病并发症（包括肾衰竭和相关表型）的遗传风险因素。但是，有效使用该工具需要对遗传分析方法进行投资，又需要对表型的敏锐理解。因此，我们已经组建了一个多学科团队，包括统计遗传学家，分子遗传学家以及有关肾功能和失败的专家，并建议将各种方法应用于肾衰竭和使用Gokind样品的肾衰竭和相关定量表型的研究。具体而言，我们建议使用Illumina Hapmap 300 Beadchip平台，在Gokind Collection（2,807个个人）中的所有证据和父母的基因型； 2）数据对数据进行标准和新的遗传分析，以绘制与糖尿病性肾病和相关表型相关的基因； 3）验证基因分型并在基因或区域进行精细映射研究，以显示与糖尿病性肾病相关，相关定量表型和其他在Gokind样品中测得的糖尿病并发症的度量。鉴定基因和有助于糖尿病肾病发展的特定遗传变异将导致预防和治疗这种常见的糖尿病长期并发症的新方法。