Identification of Genes for ESRD in African Americans

非裔美国人 ESRD 基因的鉴定

• 批准号: 7279104
• 负责人: Wen Hong Linda Kao
• 金额: $ 61.45万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7279104
• 关键词: Accounting; Admixture; African American; Albumins; Alleles; Ancillary Study; Archives; Caring; Chromosome Mapping; Clinical; Collaborations; Complex; Creatinine; DNA; Development; Diabetes Mellitus; Disease; Disease susceptibility; End stage renal failure; Epidemiology; Family; Frequencies; Funding; Genes; Genetic; Genome; Genomics; Genotype; Goals; Individual; Investigation; Kidney; Kidney Diseases; Laboratories; Linkage Disequilibrium; Linkage Disequilibrium Mapping; Maps; Multicenter Studies; National Cancer Institute; Outcome; Parents; Participant; Patients; Phenotype; Predisposition; Prospective Studies; Proteins; Protocols documentation; Public Health; Recruitment Activity; Request for Applications; Research; Research Infrastructure; Research Personnel; Risk; Sampling; Single Nucleotide Polymorphism; Staging; Susceptibility Gene; System; Techniques; Testing; Urine; cardiovascular risk factor; case control; density; design; diabetic; experience; genetic analysis; genetic epidemiology; genetic linkage analysis; genome wide association study; genotyping technology; innovation; insight; multidisciplinary; novel; programs

DESCRIPTION (provided by applicant): End stage renal disease (ESRD) is a major clinical and public health problem, especially in African Americans. This proposal is an ancillary study to the NIH-NIDDK funded Family Investigation of Diabetes and Nephropathy (FIND) and the Choices for Healthy Outcomes in Caring for ESRD patients (CHOICE) studies, ongoing multicenter studies to identify susceptibility genes for nephropathy (FIND), and risk factors for cardiovascular outcomes in ESRD patients (CHOICE). 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. To achieve this goal, we will employ Mapping by Admixture Linkage Disequilibrium (MALD) analysis, a specialized form of linkage disequilibrium mapping, to perform a genome-wide association study in approximately 2,500 African-American participants who have already been recruited and characterized with respect to renal phenotypes and had DNA collected and isolated. We hypothesize 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 ALD with ESRD susceptibility alleles. This hypothesis will be tested by comprehensively evaluating MALD markers in approximately 1,400 African-American cases with ESRD and 750 African-American controls without renal disease. We will: 1) genotype ~3,000 African-American MALD markers (1.2 cM average spacing) in DNA from approximately 2,500 African-American participants (almost 7 million genotypes) using an advanced, high-throughput genotyping system; 2) perform a genome-wide association analysis utilizing a ~1 cM dense genetic map and identify chromosomal loci that are in ALD with ESRD in a case-control design, ESRD attributable to diabetes in a case-control design, and quantitative renal phenotypes amongst 1,100 individuals without ESRD, 3) use closely-spaced SNP markers to fine map putative chromosomal region in ALD with ESRD. The proposed genetic analyses are innovative and complementary to the more traditional linkage techniques and not part of the core protocols of the parent studies. This study will provide key insights into the genetic control of susceptibility of ESRD

描述（由申请人提供）： 终末期肾病（ESRD）是一个主要的临床和公共卫生问题，特别是在非洲裔美国人。该提案是NIH-NIDDK资助的糖尿病和肾病家族调查（FIND）和ESRD患者护理健康结局选择（CHOICE）研究的辅助研究，正在进行的多中心研究，以确定肾病易感基因（FIND）和ESRD患者心血管结局的风险因素（CHOICE）。 这项提案的总体目标是确定新的基因座，并最终基因，这可能部分地解释了非洲裔美国人与白人相比ESRD的过度风险。为了实现这一目标，我们将采用混合物连锁不平衡（MALD）分析，一种特殊形式的连锁不平衡作图，在大约2,500名非洲裔美国人参与者中进行全基因组关联研究，这些参与者已经招募并表征了肾脏表型，并收集和分离了DNA。我们假设，一些肾脏疾病的易感性等位基因在非洲裔美国人中的频率高于白人，并且非洲裔美国人基因组的特定区域包含ALD与ESRD易感性等位基因的标记等位基因。这一假设将通过全面评估大约1,400例非洲裔美国人ESRD病例和750例非裔美国人无肾脏疾病对照的MALD标志物进行检验。我们将：1）基因型~ 3，000个非裔美国人MALD标记（1.2厘米平均间距）的DNA从大约2,500名非洲裔美国人参与者（近700万个基因型）使用先进的高通量基因分型系统; 2）利用~ 1cM密集遗传图谱进行全基因组关联分析，并在病例对照设计中鉴定ALD与ESRD的染色体基因座，在病例-对照设计中，可归因于糖尿病的ESRD，以及在1，100个没有ESRD的个体中定量肾表型，3）使用紧密间隔的SNP标记来精细定位ALD与ESRD中的推定染色体区域。 拟议的遗传分析是创新的，是对更传统的连锁技术的补充，而不是母研究核心方案的一部分。这项研究将为ESRD易感性的遗传控制提供关键的见解