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）：本研究计划是为了响应 RFA DK-06-504 的要求而提交的，以继续 NIDDK 炎症性肠病遗传学联盟 (IBDGC)。该主申请作为耶鲁大学数据协调中心申请 (DCC) 提交，描述了先前的研究成果、前瞻性研究计划以及整个 IBDGC 的运营基础设施。该 DCC 申请（首席研究员，PI：Judy H. Cho，医学博士）已与来自雪松-西奈遗传学研究中心 (CSGRC)、约翰霍普金斯大学遗传学研究中心 (JHGRC)、蒙特利尔大学遗传学研究中心（UMGRC）、匹兹堡大学遗传学研究中心（UPGRC）、多伦多大学遗传学研究中心（UTGRC）和耶鲁大学遗传学研究中心（YUGRC）。该联盟的中心目标是确定导致 IBD 发病机制的易感基因。由于具有互补技能、增强的统计能力、持续的 NIH 监督和优化的质量控制的团队的协同作用，这一巨大的挑战可以通过联盟结构得到最佳解决。第一个资助期的成果是确定了 IL23R（白细胞介素 23 受体）作为 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。在此，我们建议在现有进展的基础上全面定义 IBD 中的遗传因素。三个具体目标包括： 1）联盟资源的扩展、开发和管理。增加关键人群（包括早发病​​例）的招募将提高统计能力。 2) 采用多种方法来识别导致 IBD 易感性的遗传变异。我们提供了一种广泛的算法来跟踪初始关联信号。提议进行溃疡性结肠炎全基因组关联研究。 3) 通过了解遗传对表型表达、基因通路、基因-基因 (G x G) 和基因-环境 (G x E) 相互作用的影响，建立 IBD 风险模型。提供了用于识别表型变异的遗传预测因子的基本模型。描述了检查的具体阶段，最佳地利用统一、有力、大型联盟范围研究提供的优势，以及 GRC 主导的研究可实现的方法的更大个性化和专业化。