A genome-wide association study identifies a new locus associated with the response to anti-TNF therapy in rheumatoid arthritis

Pharmacogenomics J. 2016 Apr;16(2):147-50. doi: 10.1038/tpj.2015.31. Epub 2015 Apr 21.


Anti-Tumor Necrosis Factor (anti-TNF) drugs are biologic agents commonly used to treat rheumatoid arthritis (RA). However, anti-TNFs are not effective in approximately one out of four treated patients. We conducted a Genome-Wide Association Study (GWAS) to identify the genetic variation associated with the response to anti-TNF therapy in RA. In the discovery stage, 372 RA patients treated with an anti-TNF agent (infliximab, adalimumab or etanercept) were analyzed and treatment response was defined at 12 weeks of therapy. We found a genome-wide significant association in the MED15 gene with the response to etanercept (P<1.5e-8). Using an independent cohort of 245 RA patients, we performed a replication study of the most significant GWAS associations. We replicated the association at the MED15 locus and found suggestive evidence of association in the previously associated MAFB locus. The results of this study suggest novel mechanisms associated with the response to anti-TNF therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adalimumab / therapeutic use
  • Adult
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / genetics
  • Etanercept / therapeutic use
  • Female
  • Genetic Loci*
  • Genetic Markers
  • Genome-Wide Association Study
  • Humans
  • Infliximab / therapeutic use
  • MafB Transcription Factor / genetics
  • Male
  • Mediator Complex / genetics
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*


  • Antirheumatic Agents
  • Genetic Markers
  • MAFB protein, human
  • MED15 protein, human
  • MafB Transcription Factor
  • Mediator Complex
  • Tumor Necrosis Factor-alpha
  • Infliximab
  • Adalimumab
  • Etanercept