MALD FIND Renewal

MALD FIND 续订

• 批准号: 7126729
• 负责人: RULAN S PAREKH
• 金额: $ 15.3万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7126729
• 关键词: African American; caucasian American; chronic renal failure; clinical research; cooperative study; diabetes mellitus genetics; diabetic nephropathy; family genetics; gene mutation; genetic markers; genetic polymorphism; genetic susceptibility; genotype; health disparity; human genetic material tag; human subject; linkage disequilibriums; patient oriented research; racial /ethnic difference

DESCRIPTION (provided by applicant): End stage renal disease (ESRD) is a major clinical and public health problem, especially in African- Americans. This proposal is a renewal application for the NIH-NIDDK-funded Family Investigation of Diabetes and Nephropathy (FIND), an ongoing multicenter study to identify susceptibility genes for nephropathy. The overall objective of this proposal is to identify novel loci, and ultimately genes, that may partially account for excess risk of ESRD in African Americans compared to whites using Mapping by Admixture Linkage Disequilibrium (MALD) analysis. Our central hypothesis is that some renal disease susceptibility alleles are present at higher frequency in African-Americans than in whites and that specific regions of the genome in African-Americans contain marker alleles that are in admixture linkage disequilibrium with ESRD susceptibility alleles. MALD is a specialized form of linkage disequilibrium mapping and will be used to perform a genome-wide association study in approximately 1,500 African-American cases and 1,300 African-American controls from FIND and 250 similarly phenotyped African-American cases from the CHOICE study, also funded by NIH-NIDDK. In this proposal, we are requesting funds to recruit an additional 300 ESRD cases and 300 controls without renal disease to achieve a final sample size of approximately 3,000 cases and controls. The Johns Hopkins center differs from other FIND centers which use either a family-based linkage approach or MALD in Mexican Americans. Furthermore, it is the only FIND study site that has recruited nondiabetic ESRD cases, thus providing an opportunity to examine whether susceptibility genes are similar for diabetic and nondiabetic ESRD. Additional recruitment is justified by the need to have an adequate number of cases with nondiabetic ESRD. Genotyping for this study is funded by an RO-1 to Dr. Kao. Since FIND began, our team has developed a dense (about 3,000 markers) genome map of highly informative African-American MALD markers as well as new approaches to statistical analysis. The proposed genetic analyses are innovative and complementary to the more traditional linkage techniques used by other FIND study sites. This study will provide key insights into the genetic susceptibility of ESRD.

描述（由申请人提供）： 末期肾脏疾病（ESRD）是一个主要的临床和公共卫生问题，尤其是在非裔美国人。该建议是对NIH-NIDDK资助的糖尿病和肾病（FIND）的续签应用，这是一项正在进行的多中心研究，以识别肾病的易感基因。该提案的总体目的是确定新的基因座，最终是基因，这些基因群可能部分解释了非洲裔美国人的ESRD过量风险，而使用使用混合物链接不平衡（MALD）分析的白人相比。我们的中心假设是，与白人相比，非裔美国人的某些肾脏疾病易感性等位基因在非裔美国人的频率更高，而非裔美国人中基因组的特定区域包含与ESRD易感性等位基因相结合链接不平衡的标记等位基因。 马尔德是一种连锁不平衡映射的一种专业形式，将用于在大约1,500个非裔美国人病例和1,300个非裔美国人对照组中进行全基因组的关联研究，并从发现的250种非裔美国人对照组中进行，同样是由Nih-Nih-Niddk资助的选择研究的250种类似表型的非裔美国人病例。在此提案中，我们要求资金招募另外300例ESRD病例和300个没有肾脏疾病的对照，以达到约3,000例病例和对照的最终样本量。 约翰·霍普金斯中心（Johns Hopkins Center）不同于其他发现中心，这些中心使用基于家庭的联系方法或墨西哥裔美国人的马尔德。此外，它是唯一招募了非糖尿病ESRD病例的研究地点，因此提供了一个机会来检查易感性基因是否与糖尿病和非糖尿病性ESRD相似。需要有足够数量的非糖尿病性ESRD病例来证明额外的招聘是合理的。这项研究的基因分型由KAO博士提供的RO-1资助。 自发现开始以来，我们的团队已经开发了一个密集的（约3,000个标记）基因组图，该图具有高度信息丰富的非裔美国人MALD MARKERS以及统计分析的新方法。所提出的遗传分析是创新的，并且与其他发现研究地点使用的更传统的连锁技术互补。这项研究将为ESRD的遗传敏感性提供关键的见解。