IBD Genetics Consortium Data Coordinating Center

IBD 遗传学联盟数据协调中心

• 批准号: 7936388
• 负责人: JUDY H. CHO
• 金额: $ 39.4万
• 依托单位: YALE UNIVERSITY
• 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 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7936388
• 关键词: Admixture; African American; Algorithms; Antibodies; Biological Markers; Candidate Disease Gene; Classification; Classification Scheme; Clinical; Clinical Management; Collection; Communication; Complex; Crohn' s disease; Data; Data Coordinating Center; Development; Disease; Doctor of Medicine; European; Foundations; Functional disorder; Funding; Future; Genes; Genetic; Genetic Research; Genetic Variation; Genome; Genotype; Goals; Healed; Hereditary Disease; Individual; Inflammatory Bowel Diseases; Linkage Disequilibrium; Maps; Minority; Modeling; Molecular; National Institute of Diabetes and Digestive and Kidney Diseases; Pathogenesis; Pathway Analysis; Pathway interactions; Patients; Phenotype; Predisposition; Principal Investigator; Puerto Rican; Quality Control; Research; Research Infrastructure; Research Personnel; Resources; Risk; Role; Sampling; Serum; Signal Transduction; Staging; Structure; Study Subject; Susceptibility Gene; Ulcerative Colitis; United States National Institutes of Health; Universities; Variant; base; cohort; comparative; disorder subtype; early onset; follow-up; gene discovery; gene environment interaction; gene interaction; genetic association; genome wide association study; healing; improved; interleukin-23; lymphoblastoid cell line; meetings; programs; prospective; receptor; response; sample collection; skills

DESCRIPTION (provided by applicant): This Research Plan is submitted in response to the RFA DK-06-504 for continuing the NIDDK Inflammatory Bowel Disease Genetics Consortium (IBDGC). This Master Application, submitted as a Data Coordinating Center application (DCC) from Yale University, describes prior research accomplishments, a prospective research plan, and the operational infrastructure of the entire IBDGC. This DCC application (Principal Investigator, PI: Judy H. Cho, M.D.) has been coordinated with Genetics Research Center (GRC) applications from the Cedars-Sinai Genetics Research Center (CSGRC), the Johns Hopkins Genetics Research Center (JHGRC), the University of Montreal Genetics Research Center (UMGRC), the University of Pittsburgh Genetics Research Center (UPGRC), the University of Toronto Genetics Research Center (UTGRC), and the Yale University Genetics Research Center (YUGRC). The central goal of this Consortium is to identify susceptibility genes contributing to the pathogenesis of IBD. This large challenge is optimally met through a Consortium structure due to synergy in a group with complementary skills, enhanced statistical power, ongoing NIH oversight and optimized quality control. The showpiece of the first funding period has been the identification of IL23R (interleukin-23 receptor) as a major susceptibility gene for IBD, highlighting the significant pathogenic role of genetic variation in IBD. Here, we propose to build on present progress to comprehensively define genetic contributions in IBD. Three specific aims include: 1) Expansion, Development and Management of Consortium Resources. Increased recruitment of key cohorts, including early-onset cases, will provide improved statistical power. 2) To employ a variety of approaches to identify genetic variation that contributes to IBD susceptibility. We provide a broad algorithm for follow-up of initial association signals. An ulcerative colitis genome-wide association study is proposed. 3) To build a risk model of IBD by understanding genetic influence on variations in phenotypic expressivity, gene pathway, and gene-gene (G x G) and gene-environmental (G x E) interactions. A basic model for identifying genetic predictors of phenotypic variability is provided. Specific stages of workup, optimally utilizing the strengths provided by uniform, well-powered, large Consortium-wide studies with the greater individualization and specialization of approaches achievable with GRC-led studies are described.

描述（由申请人提供）：该研究计划是针对RFA DK-06-504提交的，用于继续NIDDK炎症性肠病遗传学财团（IBDGC）。该主应用程序是耶鲁大学作为数据协调中心应用程序（DCC）提交的，描述了先前的研究成就，前瞻性研究计划以及整个IBDGC的运营基础架构。该DCC申请（PI：Judy H. Cho，M.D。）已与遗传学研究中心（GRC）的应用协调，来自雪松 - 西奈遗传学研究中心（CSGRC），约翰斯·霍普金斯遗传学研究中心（JHGRC），蒙特雷尔遗传学研究中心（UPGRC），UPGRC，UPITBUN，PITSBUN GUNGH GENTIC SENTICER研究中心（JHGRC）多伦多遗传学研究中心（UTGRC）和耶鲁大学遗传学研究中心（YUGRC）。该财团的核心目标是确定有助于IBD发病机理的敏感性基因。由于具有互补技能，增强统计能力，正在进行的NIH监督和优化质量控制的团队的协同作用，因此通过财团结构通过财团结构进行了最佳挑战。第一个融资期的展示是将IL23R（白介素23受体）鉴定为IBD的主要易感基因，强调了遗传变异在IBD中的重要致病作用。在这里，我们建议以当前进展为基础，以全面定义IBD中的遗传贡献。三个具体目标包括：1）财团资源的扩展，开发和管理。包括早发病​​例在内的关键队列的招募增加将提供改善的统计能力。 2）采用多种方法来确定有助于IBD易感性的遗传变异。我们提供了一种广泛的算法，用于随访初始关联信号。提出了一项溃疡性结肠炎全基因组关联研究。 3）通过了解对表型表达，基因途径和基因基因（G x G）和基因 - 环境（G x e）相互作用的遗传影响的遗传影响来建立IBD的风险模型。提供了一个基本模型，用于识别表型变异性的遗传预测因子。描述了通过统一，驱动的大型联盟范围的研究提供的优势，并在最佳的情况下进行了特定的工作阶段，并描述了可以通过GRC领导的研究获得更大的个性化和专业化的方法。