Clinical response to methotrexate (MTX) treatment for children with juvenile idiopathic arthritis (JIA) displays considerable heterogeneity. Currently, there are no reliable predictors to identify non-responders: earlier identification could lead to a targeted treatment. We genotyped 759 JIA cases from the UK, the Netherlands and Czech Republic. Clinical variables were measured at baseline and 6 months after start of the treatment. In Phase I analysis, samples were analysed for the association with MTX response using ordinal regression of ACR-pedi categories and linear regression of change in clinical variables, and identified 31 genetic regions (P<0.001). Phase II analysis increased SNP density in the most strongly associated regions, identifying 14 regions (P<1 × 10 -5): three contain genes of particular biological interest (ZMIZ1, TGIF1 and CFTR). These data suggest a role for novel pathways in MTX response and further investigations within associated regions will help to reach our goal of predicting response to MTX in JIA. © 2014 Macmillan Publishers Limited All rights reserved.
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Cobb, J., Cule, E., Moncrieffe, H., Hinks, A., Ursu, S., Patrick, F., … Thomson, W. (2014). Genome-wide data reveal novel genes for methotrexate response in a large cohort of juvenile idiopathic arthritis cases. Pharmacogenomics Journal, 14(4), 356–364. https://doi.org/10.1038/tpj.2014.3
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