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.
| Kastner, Daniel L; Aksentijevich, Ivona; Goldbach-Mansky, Raphaela (2010) Autoinflammatory disease reloaded: a clinical perspective. Cell 140:784-90 |
