NIDDK IBD Genetics Consortium Genetic Research Center

NIDDK IBD 遗传学联盟遗传研究中心

• 批准号: 7932316
• 负责人: Richard H Duerr
• 金额: $ 33.78万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7932316
• 关键词: Abbreviations; Affect; Biological; Chronic; Clinical Data; Colitis; Complex; Crohn' s disease; DNA; DNA Resequencing; Data; Data Coordinating Center; Data Linkages; Development; Disease; Disease susceptibility; European; Gastrointestinal tract structure; Gene Frequency; Gene-Modified; Genes; Genetic; Genetic Research; Genetic Variation; Genomics; Goals; Haplotypes; Hereditary Disease; Homologous Gene; IL12B gene; IL12RB1 gene; IRAK4 gene; Individual; Inflammatory; Inflammatory Bowel Diseases; Inherited; Intellectual Property; Interleukin 12 Receptor Beta; Keratin; Leadership; Manuals; Maps; Medical; Medical center; Minor; Modeling; National Institute of Diabetes and Digestive and Kidney Diseases; Nonmuscle Myosin Type IIA; Operative Surgical Procedures; Parents; Pathogenesis; Pathway Analysis; Pathway interactions; Persons; Phenotype; Preventive; Principal Investigator; Publications; Recruitment Activity; Research; Research Personnel; Research Proposals; Resources; Risk; Role; Sampling; Selection for Treatments; Serum; Single Nucleotide Polymorphism; Susceptibility Gene; Testing; Therapeutic Intervention; Ulcerative Colitis; Universities; Variant; Whole Blood; Work; case control; disorder risk; early onset; follow-up; gene interaction; genetic risk factor; genome wide association study; human IL12B protein; human IRAK4 protein; interleukin-23; lymphoblastoid cell line; novel; programs; receptor; repository; response; transmission process

DESCRIPTION (provided by applicant): This application is submitted in response to RFA DK-06-504 to continue the efforts of the Inflammatory Bowel Disease Genetics Consortium and our role as a Genetic Research (GRC) with the central goal of identifying susceptibility genes contributing to the pathogenesis of inflammatory bowel disease (IBD). This will be accomplished through the following specific aims. Specific Aim 1: Expansion, Development and Management of Consortium Resources. Our GRC will recruit additional IBD cases, controls, and parents with a focus on ulcerative colitis and early onset cases. Extensive clinical data will be collected on recruited subjects and biospecimens (EBV-transformed lymphoblastoid cell lines, DNA, serum, whole blood) will be ascertained and stored at the NIDDK Genetics Repository for use by the Consortium, individual GRCs and outside investigators. Specific Aim 2: To employ a variety of approaches to identify genetic variation that contributes to IBD susceptibility. Our GRC will be involved in the follow-up of European ancestry genome-wide association study results. A particular initial focus of our GRC will be on a) integrating the suggestive linkage data and genome-wide association data in the IBD2 linkage region followed by additional association mapping within IBD2, and b) a resequencing, detailed haplotype and additional association study of the IL23R gene region. Specific Aim 3: To build a risk model of IBD through understanding genetic influence on variations in phenotypic expressivity, gene pathway analysis, and gene-gene (G x G) and gene-environmental (G x E) interactions. A particular initial focus of our GRC will be on gene-gene interaction analyses and pathway analyses of genes along the IL23R pathway. Our GRC may also take on other projects as genes/genomic regions advance to confirmed evidence for contribution to disease through follow-up of the Consortium's genome-wide association data. IBD is a chronic inflammatory disease of the gastrointestinal tract which primarily affects young people and is characterized by long-term illness and the need for potent medical therapy and substantial surgical therapy. The work of the IBD Genetics Consortium will enable us to identify important predisposing and disease modifying genes contributing to the pathogenesis of IBD which has the promise to: (1) identify persons at risk for disease, (2) predict disease course, (3) aid in selection of treatment, (4) understand pathophysiologic mechanisms such that novel preventive and therapeutic interventions can be developed. Advances in IBD gene identification and methodologic approaches may also be applicable to other complex genetic disorders.

描述（由申请人提供）：该申请是针对RFA DK-06-504提交的，以继续炎症性肠病遗传学财团的努力，以及我们作为遗传研究（GRC）的作用，旨在识别有助于炎症性肠病病原体（IBD）的易感基因。这将通过以下特定目标来实现。特定目的1：财团资源的扩展，开发和管理。我们的GRC将招募其他IBD病例，对照和父母，重点是溃疡性结肠炎和早期发作病例。将收集广泛的临床数据，以招募受试者和生物测量（EBV转换的淋巴细胞细胞系，DNA，血清，全血）收集，并将在NIDDK遗传学存储库中进行确定并存储，以供联盟，单个GRC和外部研究人员使用。特定目的2：采用多种方法来识别有助于IBD易感性的遗传变异。我们的GRC将参与欧洲祖先全基因组关联研究结果的随访。我们的GRC的一个特殊初始重点将是a）在IBD2连锁区域中整合暗示性的联系数据和全基因组关联数据，然后在IBD2中进行其他关联映射，b）对IL23R基因区域的重新陈述，详细的单倍型和其他关联研究。特定目的3：通过了解对表型表达，基因途径分析以及基因基因（G x G）和基因环境（G x e）相互作用的遗传影响，建立IBD的风险模型。我们的GRC的特定初始重点将是沿IL23R途径的基因的基因相互作用分析和途径分析。我们的GRC还可以通过其他项目进行其他项目，因为基因/基因组区域通过随访，以确认对疾病的贡献证据。 IBD是胃肠道的一种慢性炎症性疾病，主要影响年轻人，其特征是长期疾病，需要有效的医疗治疗和实质性的手术治疗。 IBD遗传学联盟的工作将使我们能够确定有助于IBD发病机理的重要诱发和疾病的重要疾病，该基因有望：（1）确定患有疾病风险的人，（2）预测治疗方法，（3）有助于选择治疗的选择，（4）理解这种新型的预防性且具有新的预防性互动率。 IBD基因鉴定和方法学方法的进步也可能适用于其他复杂的遗传疾病。