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）： 在这项NIH Recovery Act用于竞争性修订申请建议中，我们建议利用NIDDK资助的慢性肾功能不全队列（CRIC）研究可提供的独特丰富数据集，因为其与其与慢性肾脏疾病进展相关的更好理解因素（CKD）相关的主要目标相关。目的是通过添加全面的基因分型来显着扩大原始研究的范围，作为在渐进式CKD和相关结果的背景下进行研究的关键变量的附加维度。我们的主要假设是，身份不明的基因变体对已建立CKD受试者的肾脏功能的可变进行性丧失显着贡献。 CRIC研究是一项庞大的前瞻性，多中心的CKD队列，有3939名参与者。我们计划在3750名参与者上完成全基因组的基因分型，他们同意使用Affymetrix（R）6.0阵列进行遗传研究。我们将能够利用众多CKD风险因素和中间表型的串行标准化测量，并计划与肾脏结局相关联的SNP标记和拷贝数变体，包括肾小球过滤率的变化，终末期肾脏疾病的发展时间的变化，以及cinstatin的测量路径的变化以及我们将在cintatatin C的变化中调查潜在的PATERACE和“鉴定”的变化，我们将识别替代基因的替代品，而我们的替代品的变化很高。所有统计分析将在白人（CEU）和非裔美国人（AA）参与者中分别进行。我们将使用代表没有CKD的高加索人和AA受试者的几项大型队列研究获得现有的全基因组结果来复制我们的发现。 相关性：预计这项研究的结果将增加我们的理解，对进行性CKD和相关结果的遗传基础。