Genome-wide data reveal novel genes for methotrexate response in a large cohort of juvenile idiopathic arthritis cases

J. Cobb*, E. Cule, H. Moncrieffe, A. Hinks, S. Ursu, F. Patrick, L. Kassoumeri, E. Flynn, M. Bulatović, N. Wulffraat, B. Van Zelst, R. De Jonge, M. Bohm, P. Dolezalova, S. Hirani, S. Newman, P. Whitworth, T. R. Southwood, M. De Iorio, L. R. WedderburnW. Thomson

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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.

Original languageEnglish
Pages (from-to)356-364
Number of pages9
JournalPharmacogenomics Journal
Issue number4
Publication statusPublished - Aug 2014

Cite this