Genome Wide Association of Renal Progression in the CRIC Study

CRIC 研究中肾脏进展的全基因组关联

• 批准号: 7814547
• 负责人: HAROLD I FELDMAN
• 金额: $ 210万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7814547
• 关键词: African; African American; Aging; American; Atherosclerosis; Baltimore; Biological; Blood Pressure; Caucasians; Caucasoid Race; Chronic Kidney Failure; Chronic Kidney Insufficiency; Clinical; Cohort Studies; Communities; Computer Simulation; Consent; Creatinine; Data; Data Set; Development; Diabetes Mellitus; Dimensions; Disease Outcome; Disease Progression; Economics; End stage renal failure; Equation; European; Event; Funding; Genetic; Genetic Variation; Genomics; Genotype; Glomerular Filtration Rate; Goals; Health; Heart; Hypertension; Individual; Iothalamate; Kidney; Kidney Diseases; Laboratory Technicians; Longitudinal Studies; Measurement; Measures; Mediating; Modification; Outcome; Participant; Pathway interactions; Phenotype; Principal Investigator; Production; Proteinuria; Recovery; Renal function; Renin-Angiotensin System; Risk; Risk Factors; Serum; Severities; Single Nucleotide Polymorphism; Subgroup; Therapeutic Intervention; Time; United States National Institutes of Health; Variant; base; caucasian American; cohort; disorder risk; follow-up; genetic variant; genome wide association study; genome-wide; inhibitor/antagonist; insight; novel; post gamma-globulins; prospective

DESCRIPTION (provided by applicant): In this NIH Recovery Act Funds for Competitive Revision Application proposal, we propose to leverage the unique rich data set available from the NIDDK-funded Chronic Renal Insufficiency Cohort (CRIC) study, as related to its principal aims of better understanding factors associated with progression of chronic kidney disease (CKD). The goal is to significantly expand the scope of the original study by adding comprehensive genotyping as an added dimension of critical variables to be studied in the context of progressive CKD and related outcomes. Our primary hypothesis is that unidentified gene variants contribute significantly to the variable progressive loss of renal function in subjects with established CKD. The CRIC study is a large prospective, multi-center, CKD cohort with 3939 participants. We plan to complete a genome-wide genotyping on 3750 participants who have consented for genetic studies using the Affymetrix(R) 6.0 array. We will be able to take advantage of the serial standardized measurement of numerous CKD risk factors and intermediate phenotypes and plan to associated SNP markers and copy number variants with renal outcomes including change in glomerular filtration rate, time to development of end-stage renal disease, and change in measures of cystatin C. We will also investigate potential pathways and effect modifiers of our top identified gene variants. All statistical analyses will be undertaken separately within white (CEU) and African American (AA) participants. We will replicate our findings in silico using existing genome-wide results available from several large cohort studies representing Caucasian and AA subjects without CKD. RELEVANCE: The results from this study is expected to increase our understanding the genetic underpinning of progressive CKD and associated outcomes.

描述（由申请人提供）： 在这个NIH恢复法案基金竞争性修订申请提案中，我们建议利用NIDDK资助的慢性肾功能不全队列（CRIC）研究中提供的独特丰富的数据集，因为其主要目的是更好地了解与慢性肾脏病（CKD）进展相关的因素。我们的目标是通过增加全面的基因分型作为在进行性CKD和相关结局背景下研究的关键变量的额外维度来显著扩大原始研究的范围。我们的主要假设是，未鉴定的基因变异对已确诊的CKD受试者的可变进行性肾功能丧失有显著影响。CRIC研究是一项大型前瞻性、多中心、CKD队列研究，共有3939名受试者。我们计划对3750名同意使用Affytron（R）6.0阵列进行遗传研究的参与者进行全基因组基因分型。我们将能够利用众多CKD风险因素和中间表型的系列标准化测量，并计划将SNP标记物和拷贝数变异与肾脏结局（包括肾小球滤过率的变化、发展为终末期肾病的时间以及胱抑素C测量的变化）相关联。我们还将研究我们最常见的基因变异的潜在途径和效应调节剂。将在白色（CEU）和非洲裔美国人（AA）受试者中单独进行所有统计分析。我们将使用来自代表无CKD的高加索人和AA受试者的几项大型队列研究的现有全基因组结果，通过计算机模拟复制我们的发现。 相关性：这项研究的结果有望增加我们对进展性CKD及其相关结局的遗传基础的理解。