Genetics and Pathophysiology of Systemic Onset Juvenile Idiopathic Arthritis

全身性幼年特发性关节炎的遗传学和病理生理学

基本信息

批准号：
8175283
负责人：
Daniel Kastner
金额：
$ 96.99万
依托单位：
NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/8175283
关键词：
16 year old Accounting Age of Onset Argentina Arthritis Australia Biochemical Bioinformatics Brazil Candidate Disease Gene Child Childhood Chronic Chronic Childhood Arthritis Clinical Clinical Trials Color Complex Computer Simulation Cytokine Gene DNA Data Analyses Databases Disease Disseminated Intravascular Coagulation Ensure Enzymes Etiology Europe Exanthema Family Fever Frequencies Functional disorder Genetic Genetic Polymorphism Genotype Goals Hospitals Housing Human Inflammation Inflammatory Informed Consent Institutes International Joints Laboratories Life Light Liver London Lymphatic Diseases Macrophage Activation Major Histocompatibility Complex Medical center Meleagris gallopavo North America Odds Ratio Paris, France Patients Pattern Phenotype Philadelphia Predisposition Prevalence Recruitment Activity Regulation Reporting Research Personnel Rheumatoid Arthritis Rheumatology Risk Running Salmon Sampling Sampling Studies Serositis Serum Specimen Spleen Syndrome Turkey bird United States National Institutes of Health Universities Utah base boys cohort genome wide association study genome-wide analysis girls meetings new therapeutic target thrombocytosis tool trait

项目摘要

During the reporting period we have established an international consortium for the purpose of identifying and obtaining DNA specimens from at least 1000 well-characterized cases of systemic onset JIA and 1000 ethnically-matched controls. This includes investigators from several of the major pediatric rheumatology centers in North America, including the Childrens Hospital of Philadelphia, Cincinnati Childrens Hospital Medical Center, the Hospital for Sick Children in Toronto, Stanford University, and the University of Utah; from several of the major pediatric rheumatology centers in Europe, including Great Ormand Street Hospital in London, Hopital Necker-Enfants Malades in Paris, the Gaslini Institute in Genova, and the Wilhelmena Hospital in Utrecht; and other centers in Turkey, Argentina, Brazil, and Australia. In early May, 2010, we hosted a meeting of international collaborators at the NIH, in which there were discussions regarding recruitment strategies, appropriate informed consent for genome-wide association studies (GWAS), sample shipment, genotyping, and data analysis. Because of the difficulties for some centers to recruit appropriate ethnically matched controls, where necessary in silico controls will be drawn from existing online databases, using bioinformatic tools to ensure appropriate matching by ancestry. The current plan is for all genotyping to take place at the NIH, using Illumina Human Omni 1M-Quad, v1.0 bead chips and an Illumina iScan Beadarray scanner housed in the Laboratory of Clinical Investigation. To date, we have genotyped 747 study samples, 444 cases and 303 controls. This includes 208 cases and 207 controls from Cincinnati, 108 cases from the UK, 54 cases and 96 controls from Turkey, 42 cases from Utah, and 32 cases from Stanford. Overall, 98% of these samples had greater than a 99% genotype call-rate. During the next year we anticipate genotyping a similar number of cases to the number genotyped this year, bringing the total of cases close to the target of 1000.

在报告期内，我们成立了一个国际联盟，目的是从至少 1000 个特征明确的系统性 JIA 病例和 1000 个种族匹配的对照中识别和获取 DNA 样本。其中包括来自北美几个主要儿科风湿病中心的研究人员，包括费城儿童医院、辛辛那提儿童医院医疗中心、多伦多病童医院、斯坦福大学和犹他大学；来自欧洲几家主要的儿科风湿病中心，包括伦敦的大奥曼德街医院、巴黎的内克尔儿童马拉德医院、热那亚的加斯利尼研究所和乌得勒支的威廉梅纳医院；以及土耳其、阿根廷、巴西和澳大利亚的其他中心。 2010 年 5 月初，我们在 NIH 主办了一次国际合作者会议，会议讨论了招募策略、全基因组关联研究 (GWAS) 的适当知情同意、样本运输、基因分型和数据分析。由于一些中心很难招募适当的种族匹配对照，必要时将从现有的在线数据库中提取计算机对照，使用生物信息学工具确保按血统进行适当匹配。目前的计划是所有基因分型均在 NIH 进行，使用临床研究实验室中的 Illumina Human Omni 1M-Quad、v1.0 微珠芯片和 Illumina iScan Beadarray 扫描仪。迄今为止，我们已经对 747 个研究样本、444 个病例和 303 个对照进行了基因分型。其中包括来自辛辛那提的 208 例病例和 207 例对照病例、来自英国的 108 例病例、来自土耳其的 54 例病例和 96 例对照病例、来自犹他州的 42 例病例和来自斯坦福大学的 32 例病例。总体而言，这些样本中 98% 的基因型检出率高于 99%。我们预计明年对病例进行基因分型的数量与今年相似，使病例总数接近 1000 例的目标。