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A genome-wide association study identifies a new locus associated with the response to anti-TNF therapy in rheumatoid arthritis
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A genome-wide association study identifies a new locus associated with the response to anti-TNF therapy in rheumatoid arthritis
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Journal Article
A genome-wide association study identifies a new locus associated with the response to anti-TNF therapy in rheumatoid arthritis
2016
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 45/77
/ Adalimumab - therapeutic use
/ Adult
/ Antirheumatic Agents - therapeutic use
/ Arthritis, Rheumatoid - drug therapy
/ Arthritis, Rheumatoid - genetics
/ Biomedical and Life Sciences
/ Etanercept - therapeutic use
/ Female
/ Genome-wide association studies
/ Genome-Wide Association Study
/ Genomes
/ Humans
/ Identification and classification
/ Infliximab - therapeutic use
/ MafB Transcription Factor - genetics
/ Male
/ Oncology
/ Patients
/ Polymorphism, Single Nucleotide
