Two major examples of "crowdsourcing" genetic explanations for rheumatic diseases: a competition to explain the genetics of anti-TNF response in rheumatoid arthritis, and 14 newfound genes for juvenile idiopathic arthritis.
Last week's articles on rheumatology topics in the major nonspecialty journals
Crowdsourcing genetic prediction of clinical utility in the Rheumatoid Arthritis Responder Challenge Nature Genetics (2013) 45:468-469. Free full text.
A large international group of rheumatologists and geneticists has launched the Rheumatoid Arthritis Responder Challenge, a competition to find the best genetic predictor response to anti-TNF agents in rheumatoid arthritis (RA). Because (like the risk of RA development) treatment-response patterns are probably compex and involve many genes, the effort will rely on sharing of genetic datasets and algorithms on a common workspace (the Synapse platform of Sage Bionetworks). A discovery phase, building predictive models based on genome-wide association (GWAS) data from 2,700 RA patients treated with anti-TNF therapy, will be followed by a validation phase, testing each model against a different GWAS dataset from 1,100 patients. The Rheumatoid Arthritis Responder Challenge is a partnership between the Consortium of Rheumatology Researchers of North America, Inc. (CORRONA) and the US government-sponsored Pharmacogenomics Research Network. Funding has come from industry, foundation, and academic sources. A similar crowd-sourcing effort has been used previously to predict breast cancer survival from clinical and "omics" data.
Juvenile Idiopathic Arthritis
Dense genotyping of immune-related disease regions identifies 14 new susceptibility loci for juvenile idiopathic arthritisNature Genetics, online first, April 21, 2013. Full text $32
Forty collaborating pediatric rheumatology centers in the US, UK, and Germany have found 14 new genes associated with juvenile idiopathic arthritis (JIA). Only three genes were known previously for JIA, which has a strong inherited component. The study was done with a custom gene chip designed for autoimmune diseases, based on experience with 12 other autoimmune diseases, with particularly dense coverage of the HLA region. The HLA region explains 13% of the risk. The interleukin-2 pathway was also important. There was strong overlap with rheumatoid arthritis, type 1 diabetes, and celiac disease. The study examined two subtypes of JIA, oligoarticular and RFFF-negative polyarticular JIA, which had similar expression except for one region.
Case Records of the Massachusetts General Hospital. Case 13-2013: A 6-Year-Old Girl with Bone and Joint Pain and Abdominal DistentionN Engl J Med, April 25, 2013. Full text $15
A 6-Year-Old Girl with Bone and Joint Pain
NOW@NEJM, April 26, 2013. Free full text
Patients referred to rheumatology centers and later found to have cancer most commonly have (by frequency) leukemia, neuroblastoma, lymphoma, and Ewing’s sarcoma, says the discussion section in this case study of a six-year-old girl referred to a rheumatology clinic after a fall on a knee remained painful. She was admitted with one-year history of bone and joint pain, recent fever and abdominal distention. The history fit a rheumatologic condition such as JIA, but the acute presentation suggested a malignant condition. Dr. Michael J. Kelly explains the differential diagnosis that pointed to B-cell lymphoblastic leukemia-lymphoma.