MALD FIND Renewal

MALD FIND 续订

• 批准号: 7408938
• 负责人: RULAN S PAREKH
• 金额: $ 1.5万
• 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/7408938
• 关键词: Accounting; Admixture; African; African American; Alleles; Caring; Chromosome Mapping; Clinical; Collaborations; Complex; DNA; Data; Data Analyses; Development; Diabetes Mellitus; Disease; Disease susceptibility; End stage renal failure; Enrollment; Epidemiology; Family; Frequencies; Funding; Genes; Genetic; Genetic Predisposition to Disease; Genome; Genome Mappings; Genotype; Investigation; Kidney Diseases; Linkage Disequilibrium; Linkage Disequilibrium Mapping; Maps; Mexican Americans; Multicenter Studies; National Institute of Diabetes and Digestive and Kidney Diseases; Numbers; Outcome; Parents; Participant; Phenotype; Predisposition; Public Health; Recruitment Activity; Request for Proposals; Research; Research Personnel; Risk; Sample Size; Site; Staging; Susceptibility Gene; System; Techniques; Testing; base; case control; density; design; diabetic; disorder control; experience; genetic analysis; genetic epidemiology; genetic linkage analysis; genome wide association study; genotyping technology; innovation; insight; multidisciplinary; non-diabetic; novel; novel strategies; programs

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-Americansthan 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.

末期肾脏疾病（ESRD）是一个主要的临床和公共卫生问题，尤其是在非洲 美国人。该提案是NIH-NIDDK资助的家庭调查的续签申请 糖尿病和肾病（发现），这是一项正在进行的多中心研究，以识别易感基因 肾病。该提议的总体目的是确定可能 与白人使用映射相比 混合连锁不平衡（MALD）分析。我们的中心假设是一些肾脏疾病 在白人中，非洲裔美国人的易感性等位基因存在较高的频率 非裔美国人中基因组的区域包含与混合链接的标记等位基因 与ESRD易感性等位基因不平衡。 马尔德是一种连锁不平衡映射的专业形式，将用于执行基因组 - 大约1,500例非裔美国人案件和1,300名非裔美国人对照组进行的广泛协会研究 从发现和250种类似表型的非裔美国人案件中，从选择研究中也由 NIH-NIDDK。在此提案中，我们要求资金招募另外300个ESRD案件和300个案件 没有肾脏疾病的对照，达到了大约3,000例病例和对照的最终样本量。 约翰·霍普金斯中心与使用基于家庭的联系的其他发现中心不同 墨西哥裔美国人的接近或马尔德。此外，它是唯一招募的研究网站 非糖尿病ESRD病例，因此提供了一个机会来检查敏感性基因是否相似 用于糖尿病和非糖尿病性ESRD。额外的招聘是合理的 非糖尿病性ESRD病例数。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高度密集（约3,000个标记）的基因组图 信息丰富的非裔美国人马尔德标记以及统计分析的新方法。这 提出的遗传分析是创新的，并且与更传统的连锁技术互补 由其他查找研究地点使用。这项研究将为ESRD的遗传敏感性提供关键的见解。

项目成果

Genetic epidemiology of chronic kidney disease.

慢性肾脏病的遗传流行病学。

• DOI: 10.1097/mnh.0b013e328338185f
• 发表时间: 2010
• 期刊: Current opinion in nephrology and hypertension
• 影响因子: 3.2
• 作者: Estrella,MichelleM;Sperati,ChistopherJ;Kao,WenHL;Parekh,RulanS
• 通讯作者: Parekh,RulanS

Re-Sequencing of the APOL1-APOL4 and MYH9 Gene Regions in African Americans Does Not Identify Additional Risks for CKD Progression.

• DOI: 10.1159/000439448
• 发表时间: 2015
• 期刊: American journal of nephrology
• 影响因子: 4.2
• 作者: Hawkins GA;Friedman DJ;Lu L;McWilliams DR;Chou JW;Sajuthi S;Divers J;Parekh RS;Li M;Genovese G;Pollack MR;Hicks PJ;Bowden DW;Ma L;Freedman BI;Langefeld CD
• 通讯作者: Langefeld CD