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 genome-wide 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 ZMIZ1, 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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  1. 1.

    Singh JA, Saag KG, Bridges SL Jr, Akl EA, Bannuru RR, Sullivan MC, et al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol. 2016;68:1–26.

  2. 2.

    van Vollenhoven RF. Treatment of rheumatoid arthritis: state of the art 2009. Nat Rev Rheumatol. 2009;5:531–41.

  3. 3.

    Smolen JS, Aletaha D, Bijlsma JW, Breedveld FC, Boumpas D, Burmester G, et al. Treating rheumatoid arthritis to target: recommendations of an international task force. Ann Rheum Dis. 2010;69:631–7.

  4. 4.

    Schoels M, Knevel R, Aletaha D, Bijlsma JW, Breedveld FC, Boumpas DT, et al. Evidence for treating rheumatoid arthritis to target: results of a systematic literature search. Ann Rheum Dis. 2010;69:638–43.

  5. 5.

    Stoffer MA, Schoels MM, Smolen JS, Aletaha D, Breedveld FC, Burmester G, et al. Evidence for treating rheumatoid arthritis to target: results of a systematic literature search update. Ann Rheum Dis. 2016;75:16–22.

  6. 6.

    Hyrich KL, Watson KD, Silman AJ, Symmons DP, British Society for Rheumatology Biologics R. Predictors of response to anti-TNF-alpha therapy among patients with rheumatoid arthritis: Results from the British Society for Rheumatology Biologics Register. Rheumatology (Oxford). 2006;45:1558–65.

  7. 7.

    Dervieux T, Greenstein N, Kremer J. Pharmacogenomic and metabolic biomarkers in the folate pathway and their association with methotrexate effects during dosage escalation in rheumatoid arthritis. Arthritis Rheum. 2006;54:3095–103.

  8. 8.

    Lee YC, Cui J, Costenbader KH, Shadick NA, Weinblatt ME, Karlson EW. Investigation of candidate polymorphisms and disease activity in rheumatoid arthritis patients on methotrexate. Rheumatology (Oxford). 2009;48:613–7.

  9. 9.

    Jekic B, Lukovic L, Bunjevacki V, Milic V, Novakovic I, Damnjanovic T, et al. Association of the TYMS 3G/3G genotype with poor response and GGH 354GG genotype with the bone marrow toxicity of the methotrexate in RA patients. Eur J Clin Pharmacol. 2013;69:377–83.

  10. 10.

    Lima A, Monteiro J, Bernardes M, Sousa H, Azevedo R, Seabra V, et al. Prediction of methotrexate clinical response in Portuguese rheumatoid arthritis patients: implication of MTHFR rs1801133 and ATIC rs4673993 polymorphisms. Biomed Res Int. 2014;2014:368681.

  11. 11.

    Plant D, Wilson AG, Barton A. Genetic and epigenetic predictors of responsiveness to treatment in RA. Nat Rev Rheumatol. 2014;10:329–37.

  12. 12.

    Kung TN, Dennis J, Ma Y, Xie G, Bykerk V, Pope J, et al. RFC1 80G A is a genetic determinant of methotrexate efficacy in rheumatoid arthritis: a human genome epidemiologic review and meta-analysis of observational studies. Arthritis Rheumatol. 2014;66:1111–20.

  13. 13.

    Senapati S, Singh S, Das M, Kumar A, Gupta R, Kumar U, et al. Genome-wide analysis of methotrexate pharmacogenomics in rheumatoid arthritis shows multiple novel risk variants and leads for TYMS regulation. Pharmacogenet Genomics. 2014;24:211–9.

  14. 14.

    Cobb J, Cule E, Moncrieffe H, Hinks A, Ursu S, Patrick F, et al. Genome-wide data reveal novel genes for methotrexate response in a large cohort of juvenile idiopathic arthritis cases. Pharmacogenomics J. 2014;14:356–64.

  15. 15.

    Barton A, Pitzalis C. Stratified medicine in rheumatoid arthritis-the MATURA programme. Rheumatology (Oxford). 2016;56:1247–50.

  16. 16.

    Conaghan PG, Hensor EM, Keenan AM, Morgan AW, Emery P, Consortium Y. Persistently moderate DAS-28 is not benign: loss of function occurs in early RA despite step-up DMARD therapy. Rheumatology (Oxford). 2010;49:1894–9.

  17. 17.

    Sergeant JC, Hyrich KL, Anderson J, Kopec-Harding K, Hope HF, Barton A, et al. OP0013 prediction of non-response to methotrexate therapy in the Rheumatoid Arthritis Medication Study (RAMS). Ann Rheum Dis. 2016;75:57–58.

  18. 18.

    Dumitru RB, Horton S, Hodgson R, Wakefield RJ, Hensor EM, Emery P, et al. A prospective, single-centre, randomised study evaluating the clinical, imaging and immunological depth of remission achieved by very early versus delayed Etanercept in patients with Rheumatoid Arthritis (VEDERA). BMC Musculoskelet Disord. 2016;17:61.

  19. 19.

    Nam JL, Villeneuve E, Hensor EM, Conaghan PG, Keen HI, Buch MH, et al. Remission induction comparing infliximab and high-dose intravenous steroid, followed by treat-to-target: a double-blind, randomised, controlled trial in new-onset, treatment-naive, rheumatoid arthritis (the IDEA study). Ann Rheum Dis. 2014;73:75–85.

  20. 20.

    Nam JL, Villeneuve E, Hensor EM, Wakefield RJ, Conaghan PG, Green MJ, et al. A randomised controlled trial of etanercept and methotrexate to induce remission in early inflammatory arthritis: the EMPIRE trial. Ann Rheum Dis. 2014;73:1027–36.

  21. 21.

    Choy EH, Smith CM, Farewell V, Walker D, Hassell A, Chau L, et al. Factorial randomised controlled trial of glucocorticoids and combination disease modifying drugs in early rheumatoid arthritis. Ann Rheum Dis. 2008;67:656–63.

  22. 22.

    Scott IC, Ibrahim F, Simpson G, Kowalczyk A, White-Alao B, Hassell A, et al. A randomised trial evaluating anakinra in early active rheumatoid arthritis. Clin Exp Rheumatol. 2016;34:88–93.

  23. 23.

    Moreland LW, O’Dell JR, Paulus HE, Curtis JR, Bathon JM, St Clair EW, et al. A randomized comparative effectiveness study of oral triple therapy versus etanercept plus methotrexate in early aggressive rheumatoid arthritis: the treatment of Early Aggressive Rheumatoid Arthritis Trial. Arthritis Rheum. 2012;64:2824–35.

  24. 24.

    van Vollenhoven RF, Ernestam S, Geborek P, Petersson IF, Coster L, Waltbrand E, et al. Addition of infliximab compared with addition of sulfasalazine and hydroxychloroquine to methotrexate in patients with early rheumatoid arthritis (Swefot trial): 1-year results of a randomised trial. Lancet. 2009;374:459–66.

  25. 25.

    de Hair MJ, Lehmann KA, van de Sande MG, Maijer KI, Gerlag DM, Tak PP. The clinical picture of rheumatoid arthritis according to the 2010 American College of Rheumatology/European League Against Rheumatism criteria: Is this still the same disease? Arthritis Rheum. 2012;64:389–93.

  26. 26.

    Kronisch C, McLernon DJ, Dale J, Paterson C, Ralston SH, Reid DM, et al. Brief report: predicting functional disability: one-year results from the Scottish Early Rheumatoid Arthritis Inception Cohort. Arthritis Rheumatol. 2016;68:1596–602.

  27. 27.

    Jones G, Sebba A, Gu J, Lowenstein MB, Calvo A, Gomez-Reino JJ, et al. Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study. Ann Rheum Dis. 2010;69:88–96.

  28. 28.

    Emery P, Deodhar A, Rigby WF, Isaacs JD, Combe B, Racewicz AJ, et al. Efficacy and safety of different doses and retreatment of rituximab: a randomised, placebo-controlled trial in patients who are biological naive with active rheumatoid arthritis and an inadequate response to methotrexate (Study Evaluating Rituximab’s Efficacy in MTX iNadequate rEsponders (SERENE)). Ann Rheum Dis. 2010;69:1629–35.

  29. 29.

    Rubbert-Roth A, Tak PP, Zerbini C, Tremblay JL, Carreno L, Armstrong G, et al. Efficacy and safety of various repeat treatment dosing regimens of rituximab in patients with active rheumatoid arthritis: results of a Phase III randomized study (MIRROR). Rheumatology (Oxford). 2010;49:1683–93.

  30. 30.

    Tak PP, Rigby WF, Rubbert-Roth A, Peterfy CG, van Vollenhoven RF, Stohl W, et al. Inhibition of joint damage and improved clinical outcomes with rituximab plus methotrexate in early active rheumatoid arthritis: the IMAGE trial. Ann Rheum Dis. 2011;70:39–46.

  31. 31.

    Emery P, Rigby W, Tak PP, Dorner T, Olech E, Martin C, et al. Safety with ocrelizumab in rheumatoid arthritis: results from the ocrelizumab phase III program. PLoS ONE. 2014;9:e87379.

  32. 32.

    Reich D, Price AL, Patterson N. Principal component analysis of genetic data. Nat Genet. 2008;40:491–2.

  33. 33.

    Howie BN, Donnelly P, Marchini J. A flexible and accurate genotype imputation method for the next generation of genome-wide association studies. PLoS Genet. 2009;5:e1000529.

  34. 34.

    Delaneau O, Howie B, Cox AJ, Zagury JF, Marchini J. Haplotype estimation using sequencing reads. Am J Hum Genet. 2013;93:687–96.

  35. 35.

    Spiliopoulou A, Colombo M, Orchard P, Agakov F, McKeigue P. GeneImp: fast imputation to large reference panels using genotype likelihoods from ultra-low coverage sequencing. Genetics. 2017;91–104.

  36. 36.

    Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007;81:559–75.

  37. 37.

    Marchini J, Howie B, Myers S, McVean G, Donnelly P. A new multipoint method for genome-wide association studies by imputation of genotypes. Nat Genet. 2007;39:906–13.

  38. 38.

    Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–58.

  39. 39.

    Mikkelsen TS, Thorn CF, Yang JJ, Ulrich CM, French D, Zaza G, et al. PharmGKB summary: methotrexate pathway. Pharmacogenet Genomics. 2011;21:679–86.

  40. 40.

    Plenge RM, Cotsapas C, Davies L, Price AL, de Bakker PI, Maller J, et al. Two independent alleles at 6q23 associated with risk of rheumatoid arthritis. Nat Genet. 2007;39:1477–82.

  41. 41.

    Julia A, Ballina J, Canete JD, Balsa A, Tornero-Molina J, Naranjo A, et al. Genome-wide association study of rheumatoid arthritis in the Spanish population: KLF12 as a risk locus for rheumatoid arthritis susceptibility. Arthritis Rheum. 2008;58:2275–86.

  42. 42.

    Okada Y, Wu D, Trynka G, Raj T, Terao C, Ikari K, et al. Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature. 2014;506:376–81.

  43. 43.

    Kataoka H. EGFR ligands and their signaling scissors, ADAMs, as new molecular targets for anticancer treatments. J Dermatol Sci. 2009;56:148–53.

  44. 44.

    Rivera-Valentin RK, Hua YQ, Zhang Y, Lala N, Yang YW, Hughes DPM. Her-4 mediates anoikis resistance, chemoresistance, and metastatic potential in osteosarcoma. Cancer Res. 2014;74:(20 Suppl):Abstract nr A71.

  45. 45.

    Bansard C, Lequerre T, Derambure C, Vittecoq O, Hiron M, Daragon A, et al. Gene profiling predicts rheumatoid arthritis responsiveness to IL-1Ra (anakinra). Rheumatology (Oxford). 2011;50:283–92.

  46. 46.

    Martin P, McGovern A, Orozco G, Duffus K, Yarwood A, Schoenfelder S, et al. Capture Hi-C reveals novel candidate genes and complex long-range interactions with related autoimmune risk loci. Nat Commun. 2015;6:10069.

  47. 47.

    Cairns J, Freire-Pritchett P, Wingett SW, Varnai C, Dimond A, Plagnol V, et al. CHiCAGO: robust detection of DNA looping interactions in Capture Hi-C data. Genome Biol. 2016;17:127.

  48. 48.

    Wang YC, Chiang EP. Low-dose methotrexate inhibits methionine S-adenosyltransferase in vitro and in vivo. Mol Med. 2012;18:423–32.

  49. 49.

    Ellinghaus D, Ellinghaus E, Nair RP, Stuart PE, Esko T, Metspalu A, et al. Combined analysis of genome-wide association studies for Crohn disease and psoriasis identifies seven shared susceptibility loci. Am J Hum Genet. 2012;90:636–47.

  50. 50.

    International Multiple Sclerosis Genetics C, Beecham AH, Patsopoulos NA, Xifara DK, Davis MF, Kemppinen A, et al. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis. Nat Genet. 2013;45:1353–60.

  51. 51.

    Fewings NL, Gatt PN, McKay FC, Parnell GP, Schibeci SD, Edwards J, et al. The autoimmune risk gene ZMIZ1 is a vitamin D responsive marker of a molecular phenotype of multiple sclerosis. J Autoimmun. 2017;78:57–69.

  52. 52.

    Jennewein C, Zacharowski K. Abstracts of Sepsis 2012. Paris, France. November 14-16, 2012. Crit Care. 2012;16 Suppl 3:P22.

  53. 53.

    Arciuch VGA, Tedesco L, Fuertes M, Arzt E. Role of RSUME in inflammation and cancer. FEBS Lett. 2015;589:3330–5.

  54. 54.

    Sieberts SK, Zhu F, Garcia-Garcia J, Stahl E, Pratap A, Pandey G, et al. Crowdsourced assessment of common genetic contribution to predicting anti-TNF treatment response in rheumatoid arthritis. Nat Commun. 2016;7:12460.

  55. 55.

    Umicevic Mirkov M, Janss L, Vermeulen SH, van de Laar MA, van Riel PL, Guchelaar HJ, et al. Estimation of heritability of different outcomes for genetic studies of TNFi response in patients with rheumatoid arthritis. Ann Rheum Dis. 2015;74:2183–7.

  56. 56.

    van Gestel AM, Prevoo ML, van ‘t Hof MA, van Rijswijk MH, van de Putte LB, van Riel PL. Development and validation of the European League Against Rheumatism response criteria for rheumatoid arthritis. Comparison with the preliminary American College of Rheumatology and the World Health Organization/International League Against Rheumatism Criteria. Arthritis Rheum. 1996;39:34–40.

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We thank all the patients who have contributed to this research, clinical staff who supported patient recruitment and laboratory staff who undertook sample processing. We thank the Medical Research Council (MRC) and Arthritis Research UK (ARUK) for their joint funding of PEAC and MATURA (grant codes 36661 and MR/K015346/1 and 20670 & 20022 (Experimental Arthritis Treatment Centre), respectively). The RAMS cohort was part funded by ARUK (grant code 20385) and the National Institute for Health Research (NIHR) Manchester Musculoskeletal Biomedical Research Unit (BRU). The YEAR and IACON studies were part funded by program grants from ARUK (grant codes 18475 and 18387), the NIHR Leeds Musculoskeletal BRU and Diagnostic Evaluation Co-operative, the British Medical Association (Doris Hillier Award) and the Ann Wilks Charitable Foundation. The IDEA study was supported by a research grant from Investigator-Initiated Studies Program of Merck Sharp & Dohme Limited. The opinions expressed in this paper are those of the authors and do not necessarily represent those of Merck Sharp & Dohme Limited. Pfizer provided study drug and unrestricted grant funding for the EMPIRE study. The authors had the sole responsibility for data analysis and manuscript preparation. ARUK paid for the genotyping of CARDERA-1 and 2 (grant reference 19739). The SERA cohort was funded by Pfizer and the Scottish Government (ETM40), and the SERA genomic analysis was funded by the Stratified Medicine Scotland Innovation Centre (SMS-IC007). Research in the Newcastle University Musculoskeletal Research Group is supported by the National Institute for Health Research Newcastle Biomedical Research Centre based at Newcastle Hospitals NHS Foundation Trust and Newcastle University. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. I.C.S. and ST held Academic Clinical Lectureships funded by the NIHR. This article presents independent research partly funded by the NIHR. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The funders had no role in the study design, data collection and analysis, data interpretation, the writing of the manuscript or the decision to submit the manuscript for publication. B.M. holds an MRC eMedLab Medical Bioinformatics Career Development Fellowship, funded from award MR/L016311/1. Part of this project was enabled through access to the MRC eMedLab Medical Bioinformatics infrastructure (grant code MR/L016311/1) and the MRC Leeds Medical Bioinformatics infrastructure (grant code MR/L01629X/1). PAMERA was supported by the US NIH Pharmacogenomics Research Network (PGRN) funded by NIGMS (U19 GM61388) and the RIKEN Center for Integrative Medical Sciences. It was funded in part by the Biobank Japan Project, funded by the Ministry of Education, Culture, Sports, Science and Technology of Japan. Acquisition and analysis of genetic and treatment response data from the TEAR Trial were supported in part by NIH R01 AR052658 (SLB, Jr., PI) Predictors of Treatment Response in Early Aggressive RA. The Synoviomics study was supported by the Dutch Arthritis Foundation (grant NR06/1/303).

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Author notes

  1. These authors contributed equally: Ann W Morgan, Jennifer H Barrett.


  1. Leeds Institute of Cancer and Pathology, University of Leeds, and NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK

    • John C. Taylor
    • , Jenna L. Strathdee
    •  & Jennifer H. Barrett
  2. Vanderbilt University, Nashville, TN, USA

    • Tim Bongartz
  3. Arthritis Research UK Centre for Genetics and Genomics, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK

    • Jonathan Massey
    • , Darren Plant
    • , Suzanne M. M. Verstappen
    •  & Anne Barton
  4. NIHR Manchester BRC, Central Manchester Foundation Trust, Manchester, UK

    • Jonathan Massey
    • , Darren Plant
    • , Suzanne M. M. Verstappen
    •  & Anne Barton
  5. Clinical Pharmacology, William Harvey Research Institute, Queen Mary University, London, UK

    • Borbala Mifsud
  6. Centre for Population Health Sciences, Usher Institute, University of Edinburgh Old Medical School, Teviot Place, Edinburgh, UK

    • Athina Spiliopoulou
    • , Marco Colombo
    •  & Paul McKeigue
  7. Pharmatics Ltd., 9, Little France Road, Edinburgh, UK

    • Athina Spiliopoulou
    • , Peter Orchard
    •  & Felix Agakov
  8. Research Institute for Primary Care and Health Sciences, Primary Care Sciences, Keele University and Department of Rheumatology, Haywood Hospital, High Lane, Burslem, Staffordshire, UK

    • Ian C. Scott
  9. Department of Medical and Molecular Genetics, King’s College London, London, UK

    • Ian C. Scott
  10. Roche Products, Welwyn Garden City, UK

    • Jianmei Wang
  11. Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, and NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK

    • Michael Morgan
    • , Sarah Twigg
    • , Jane E. Freeston
    • , Jackie L. Nam
    • , Paul Emery
    •  & Ann W. Morgan
  12. Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge, UK

    • Michael Morgan
  13. Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK

    • Iain B. McInnes
    •  & Duncan Porter
  14. Institute of Genetic Medicine, Newcastle University, Newcastle, UK

    • Heather J. Cordell
  15. Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University and NIHR Newcastle Biomedical Research Centre in Ageing and Long Term Conditions, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK

    • John D. Isaacs
  16. University of Kentucky College of Public Health, Lexington, KY, 40536, USA

    • Donna Arnett
  17. University Medical Center Utrecht, Utrecht, The Netherlands

    • Maria J. H. de Hair
  18. Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands

    • Paul P. Tak
  19. GlaxoSmithKline, Stevenage, UK

    • Paul P. Tak
  20. Cambridge University, Cambridge, UK

    • Paul P. Tak
  21. Ghent University, Ghent, Belgium

    • Paul P. Tak
  22. Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, USA

    • Stella Aslibekyan
    •  & S. Louis Bridges
  23. Rheumatology Unit, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden

    • Ronald F. van Vollenhoven
    •  & Leonid Padyukov
  24. Barts and The London School of Medicine & Dentistry, William Harvey Research Institute, Queen Mary University, London, UK

    • Costantino Pitzalis
    •  & Michael R. Barnes
  25. Academic Department of Rheumatology, Faculty of Life Sciences and Medicine, King’s College London, London, UK

    • Andrew P. Cope
  26. RIKEN Center for Integrative Medical Sciences, Tokyo, Japan

    • Taisei Mushiroda
    •  & Michiaki Kubo
  27. Mayo Clinic, Rochester, MN, USA

    • Richard Weinshilboum


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  1. on behalf of the MATURA

    1. and PAMERA

      1. Consortia

        Conflict of interest

        Paul P Tak is an employee and shareholder of GlaxoSmithKline; GSK has not been involved in this study. Jianmei Wang is an employee of Roche Products and Felix Agakov is an employee of Pharmatics Ltd., UK. Dr. Weinshilboum is a co-founder and stockholder in OneOme LLC, a Pharmacogenomics Decision Support Company. Paul Emery has undertaken clinical trials and provided expert advice to Pfizer, MSD, Abbvie, BMS, UCB, Roche, Novartis, Samsung, Sandoz and Lilly. The authors declare no conflict of interest with the content contained in this manuscript.

        Corresponding author

        Correspondence to Ann W. Morgan.

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