Journal
PHARMACOGENOMICS JOURNAL
Volume 18, Issue 4, Pages 528-538Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41397-018-0025-5
Keywords
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Categories
Funding
- Medical Research Council (MRC) [36661, MR/K015346/1, 20670, 20022]
- Arthritis Research UK (ARUK) [36661, MR/K015346/1, 20670, 20022]
- ARUK [20385, 18475, 18387, 19739]
- National Institute for Health Research (NIHR) Manchester Musculoskeletal Biomedical Research Unit (BRU)
- NIHR Leeds Musculoskeletal BRU and Diagnostic Evaluation Co-operative
- British Medical Association (Doris Hillier Award)
- Ann Wilks Charitable Foundation
- Investigator-Initiated Studies Program of Merck Sharp Dohme Limited
- Pfizer
- Scottish Government [ETM40]
- Stratified Medicine Scotland Innovation Centre [SMS-IC007]
- National Institute for Health Research Newcastle Biomedical Research Centre based at Newcastle Hospitals NHS Foundation Trust and Newcastle University
- NIHR
- MRC eMedLab Medical Bioinformatics Career Development Fellowship [MR/L016311/1]
- MRC eMedLab Medical Bioinformatics infrastructure [MR/L016311/1]
- MRC Leeds Medical Bioinformatics infrastructure [MR/L01629X/1]
- US NIH Pharma-cogenomics Research Network (PGRN) - NIGMS [U19 GM61388]
- RIKEN Center for Integrative Medical Sciences
- Biobank Japan Project
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- NIH [R01 AR052658]
- Dutch Arthritis Foundation [NR06/1/303]
- MRC [MR/L016311/1, MR/K015346/1, G1001518, MR/L01629X/1, G0800648] Funding Source: UKRI
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Methotrexate (MTX) monotherapy is a common first treatment for rheumatoid arthritis (RA), but many patients do not respond adequately. In order to identify genetic predictors of response, we have combined data from two consortia to carry out a genome-wide study of response to MTX in 1424 early RA patients of European ancestry. Clinical endpoints were change from baseline to 6 months after starting treatment in swollen 28-joint count, tender 28-joint count, C-reactive protein and the overall 3-component disease activity score (DAS28). No single nucleotide polymorphism (SNP) reached genomewide statistical significance for any outcome measure. The strongest evidence for association was with rs168201 in NRG3 (p =10(-7) for change in DAS28). Some support was also seen for association with ZM/Z/, previously highlighted in a study of response to MTX in juvenile idiopathic arthritis. Follow-up in two smaller cohorts of 429 and 177 RA patients did not support these findings, although these cohorts were more heterogeneous.
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