Defining the complex genetics of JIA

定义幼年特发性关节炎的复杂遗传学

• 批准号: 7941791
• 负责人: SUSAN D THOMPSON
• 金额: $ 50万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-28 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7941791
• 关键词: Address; Admixture; Affect; Age; Age of Onset; Algorithms; American; Area; Autoimmune Diseases; Autoimmune Process; Childhood; Chronic Childhood Arthritis; Classification; Clinical; Collection; Complex; Complex Genetic Trait; Controlled Study; Copy Number Polymorphism; DNA; Data; Data Set; Diagnosis; Disease; European; Evaluation; Family history of; Funding; Gender; Genes; Genetic; Genomics; Genotype; Germany; Goals; Grant; HLA Antigens; Human; Immunoglobulin M; Individual; International; Joints; Laboratories; Lead; Linkage Disequilibrium; Mission; Molecular; Molecular Profiling; Musculoskeletal Diseases; National Institute of Arthritis and Musculoskeletal and Skin Diseases; Odds Ratio; Onset of illness; Other Genetics; Outcome; Pathogenesis; Pathway interactions; Patients; Phase; Phenotype; Predisposition; Principal Component Analysis; Quality Control; Reporting; Research Design; Research Personnel; Research Proposals; Rheumatism; Rheumatoid Factor; Rheumatology; Risk; Risk Factors; Sampling; Series; Single Nucleotide Polymorphism; Skin; Subgroup; Susceptibility Gene; Technology; Testing; Therapeutic; Variant; arthropathies; base; case control; cohort; college; database of Genotypes and Phenotypes; disability; disabling disease; disorder subtype; genetic association; genetic variant; genome wide association study; genome-wide; novel; prevent; programs; response; trait

DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (08): Genomics and specific Challenge Topic, 08-AR-101 Genotyping of Existing Cohorts in Rheumatic, Skin, and Musculoskeletal Diseases. Juvenile idiopathic arthritis (JIA) is the most common autoimmune rheumatic disease of childhood and represents a series of childhood arthropathies that are largely based on clinically defined phenotypes. The two most common subtypes, and the focus of this study, are the oligoarticular and IgM rheumatoid factor negative (RF-) polyarticular forms of JIA. It is hypothesized that there are multiple genetic variants that predispose an individual to JIA and that the subtypes of JIA will differ in at least some of their susceptibility traits. Markers for these traits can be identified by systematically applying high throughput genotyping and copy number technology in a case:control genome-wide association study (GWAS) design. Phase I (GWAS I) genotyping has been completed and includes 1.8 million single nucleotide polymorphisms (SNPs) or copy number markers for 946 JIA cases and 1000 controls (Affymetrix(R) Genome-Wide Human SNP Array 6.0). Through this challenge grant opportunity, a second GWAS (GWAS-II) is proposed for 1100 additional existing JIA samples available from U.S. investigators of the Consortium on Juvenile Arthritis Genetics (CJAG) and international collaborators in Germany. Phenotypic information includes ILAR classification, age at disease onset, and joint counts. Approximately 1450 out-of-study controls are available through the GAIN study will be used for comparison in association testing for GWAS-II. This additional dataset when combined with existing complementary data from GWAS-I provides an unprecedented opportunity to reveal novel risk factors for JIA and is necessary for advancement of the field. This information may eventually lead to treatments for these disabling diseases and in the long-term contribute to preventing disability. In additional, this opportunity will contribute to a fundamental shift toward molecular definitions and reevaluation of the present criteria for defining subtypes of disease. This research proposal tests the view that juvenile idiopathic arthritis or JIA, is influenced by many genes conferring susceptibility to and protection from disease. As the genetic basis of the major autoimmune rheumatic disease of childhood becomes evident, eventually the treatment of these disabling diseases will become possible with the long term aim of preventing disability.

描述（由申请人提供）：此申请涉及广泛的挑战领域（08）：基因组学和特定挑战主题，08-AR-101对风湿病，皮肤和肌肉骨骼疾病中现有同类群体的基因分型。青少年特发性关节炎（JIA）是最常见的儿童自身免疫性疾病，代表了一系列儿童期关节病，主要基于临床定义的表型。两种最常见的亚型以及这项研究的重点是JIA的寡头和IgM类风湿因子阴性（RF-）多关节形式。假设存在多种遗传变异，使个人容易成为Jia，而JIA的亚型至少在其某些易感性性状上会有所不同。这些特征的标记可以通过系统地应用高通量基因分型和拷贝数技术来识别：全基因组协会研究（GWAS）设计。第一阶段（GWAS I）基因分型已经完成，包括946例JIA病例和1000个对照组（Affymetrix（r）全基因组人类SNP阵列6.0）的180万个单核苷酸多态性（SNP）或拷贝数标记。通过这个挑战赠款机会，提议了第二个GWAS（GWAS-II）为美国少年关节炎遗传学（CJAG）和德国国际合作者的美国研究人员提供了1100个现有的JIA样品。表型信息包括ILAR分类，疾病发病年龄和关节计数。通过增益研究可获得大约1450个未成熟的控制措施，用于比较GWAS-II的关联测试。当与GWAS-I的现有补充数据结合使用时，此额外的数据集为揭示JIA的新风险因素提供了前所未有的机会，对于该领域的发展是必要的。这些信息最终可能会导致这些残疾疾病的治疗，并在长期内有助于预防残疾。另外，这种机会将有助于朝着分子定义的基本转变，并重新评估定义疾病亚型的当前标准。该研究提案测试了以下观点：少年特发性关节炎或JIA受许多基因赋予易感性和保护疾病的影响。随着儿童期主要自身免疫性风湿病的遗传基础变得明显，最终以预防残疾的长期目的将成为可能的治疗这些残疾疾病。