title: A genome-wide association study identifies a new locus associated with the response to anti-TNF therapy in rheumatoid arthritis.
abstract: 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.
authors.affiliation: Rheumatology Research Group, Vall d'Hebron Hospital Research Institute, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Julià
authors.affiliation: UGC Reumatología, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain.
authors.forename: A
authors.identifier: http://orcid.org/0000-0002-2962-9844
authors.initials: A
authors.lastname: Fernandez-Nebro
authors.affiliation: Rheumatology Service, INIBIC-Hospital Universitario A Coruña, A Coruña, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Blanco
authors.affiliation: Rheumatology Service, Hospital Universitario La Princesa, IIS Princesa, IIS La Princesa, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Ortiz
authors.affiliation: Rheumatology Service, Hospital Clínic de Barcelona, Barcelona, Spain.
authors.forename: J D
authors.initials: JD
authors.lastname: Cañete
authors.affiliation: Rheumatology Service, Hospital del Mar, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Maymó
authors.affiliation: Rheumatology Service, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Alperi-López
authors.affiliation: Rheumatology Service, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Fernández-Gutierrez
authors.affiliation: Rheumatology Service, Hospital Universitari Germans Trias i Pujol, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Olivè
authors.affiliation: Rheumatology Service, Hospital Moisès Broggi, Barcelona, Spain.
authors.forename: H
authors.initials: H
authors.lastname: Corominas
authors.affiliation: Rheumatology Service, Hospital Sant Rafael, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Erra
authors.affiliation: Rheumatology Research Group, Vall d'Hebron Hospital Research Institute, Barcelona, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Acosta-Colman
authors.affiliation: Rheumatology Research Group, Vall d'Hebron Hospital Research Institute, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Alonso
authors.affiliation: Rheumatology Research Group, Vall d'Hebron Hospital Research Institute, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: López-Lasanta
authors.affiliation: Rheumatology Research Group, Vall d'Hebron Hospital Research Institute, Barcelona, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Tortosa
authors.affiliation: Rheumatology Service, Hospital Universitario De Guadalajara, Guadalajara, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Tornero
authors.affiliation: Rheumatology Research Group, Vall d'Hebron Hospital Research Institute, Barcelona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Marsal
mesh_terms: D000068879:Adalimumab / Q000627:therapeutic use; D000328:Adult; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics; D000068800:Etanercept / Q000627:therapeutic use; D005260:Female; D056426:Genetic Loci; D005819:Genetic Markers; D055106:Genome-Wide Association Study; D006801:Humans; D000069285:Infliximab / Q000627:therapeutic use; D051258:MafB Transcription Factor / Q000235:genetics; D008297:Male; D056892:Mediator Complex / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D018501:Antirheumatic Agents; D005819:Genetic Markers; C490407:MAFB protein, human; C416944:MED15 protein, human; D051258:MafB Transcription Factor; D056892:Mediator Complex; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept