Article Text

Download PDFPDF
Concise report
A family-based genome-wide association study reveals an association of spondyloarthritis with MAPK14
  1. Félicie Costantino1,2,3,4,
  2. Alice Talpin1,2,3,5,
  3. Roula Said-Nahal4,
  4. Ariane Leboime4,
  5. Elena Zinovieva1,2,3,
  6. Diana Zelenika6,
  7. Ivo Gut6,
  8. Céline Charon6,
  9. Brigitte Izac1,2,3,
  10. Michael Weissman7,
  11. Gilles Chiocchia1,2,3,
  12. John Reveille8,
  13. Maxime Breban1,2,3,4,
  14. Henri-Jean Garchon1,2,3,9
  1. 1Faculty of Health Sciences Simone Veil, University of Versailles Saint-Quentin-en-Yvelines, Montigny-le-Bretonneux, France
  2. 2INSERM U1173 University of Versailles Saint-Quentin-en-Yvelines, Montigny-le-Bretonneux, France
  3. 3Université Paris Diderot, Sorbonne Paris Cité, Laboratoire d'Excellence, Paris, France
  4. 4Rheumatology Division, Ambroise Paré Hospital (AP-HP), Boulogne-Billancourt, France
  5. 5Department of Medicine, University of California, San Francisco, California, USA
  6. 6National Genotyping Center (CNG), Evry, France
  7. 7Rheumatology Division, Cedars-Sinai Medical Center, Los Angeles, California, USA
  8. 8Department of Rheumatology and Clinical Immunogenetics, University of Texas Health Science Center at Houston, Houston, Texas, USA
  9. 9Genetics Division, Ambroise Paré Hospital (AP-HP), Boulogne-Billancourt, France
  1. Correspondence to Professor Henri Jean Garchon, Genetics Division, Inserm U1173, Simone Veil School of Health Sciences, U Versailles Saint-Quentin, 2 avenue de la Source de la Bièvre, Montigny-le-Bretonneux 78180, France; henri-jean.garchon{at}


Objective More than 40 loci have been associated with ankylosing spondylitis (AS), but less is known about genetic associations in spondyloarthritis (SpA) as a whole. We conducted a family-based genome-wide association study (GWAS) to identify new non-major histocompatibility complex (MHC) genetic factors associated with SpA.

Methods 906 subjects from 156 French multiplex families, including 438 with SpA, were genotyped using Affymetrix 250K microarrays. Association was tested with Unphased. The best-associated non-MHC single nucleotide polymorphisms (SNPs) were then genotyped in two independent familial cohorts (including 215 French and 294 North American patients with SpA, respectively) to replicate associations.

Results 43 non-MHC SNPs yielded an association signal with SpA in the discovery cohort (p<1×10−4). In the extension studies, association was replicated at a nominal p value of p<0.05 for 16 SNPs in the second cohort and for three SNPs in the third cohort. Combined analysis identified an association close to genome-wide significance between rs7761118, an intronic SNP of MAPK14, and SpA (p=3.5×10−7). Such association appeared to be independent of HLA-B27.

Conclusions We report here for the first time a family-based GWAS study on SpA and identified an associated polymorphism near MAPK14. Further analyses are needed to better understand the functional basis of this genetic association.

  • Spondyloarthritis
  • Ankylosing Spondylitis
  • Gene Polymorphism

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Handling editor Tore K Kvien

  • MB and H-JG contributed equally.

  • Contributors All the authors contributed to the manuscript based on (1) substantial contributions to conception and design, acquisition of data or analysis and interpretation of data; (2) drafting the article or revising it critically for important intellectual content; and (3) final approval of the version to be published.

  • Funding This work was supported by grant from Agence Nationale de la Recherche (grant ANR 2010 GEMISA). Félicie Costantino was supported by a grant from the Société Française de Rhumatologie (SFR). Alice Talpin and Elena Zinovieva were supported by a grant from Arthritis Fondation Courtin.

  • Competing interests None declared.

  • Ethics approval Local ethical committees of Cochin Hospital (Paris, France), Ambroise Paré Hospital (Boulogne-Billancourt, France) and University of Texas Medical School (Houston, Texas, USA).

  • Provenance and peer review Not commissioned; externally peer reviewed.