title: A family-based genome-wide association study reveals an association of spondyloarthritis with MAPK14.
abstract: 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.
authors.affiliation: Faculty of Health Sciences Simone Veil, University of Versailles Saint-Quentin-en-Yvelines, Montigny-le-Bretonneux, France.|INSERM U1173 University of Versailles Saint-Quentin-en-Yvelines, Montigny-le-Bretonneux, France.|Université Paris Diderot, Sorbonne Paris Cité, Laboratoire d'Excellence, Paris, France.|Rheumatology Division, Ambroise Paré Hospital (AP-HP), Boulogne-Billancourt, France.
authors.forename: Félicie
authors.initials: F
authors.lastname: Costantino
authors.affiliation: Faculty of Health Sciences Simone Veil, University of Versailles Saint-Quentin-en-Yvelines, Montigny-le-Bretonneux, France.|INSERM U1173 University of Versailles Saint-Quentin-en-Yvelines, Montigny-le-Bretonneux, France.|Université Paris Diderot, Sorbonne Paris Cité, Laboratoire d'Excellence, Paris, France.|Department of Medicine, University of California, San Francisco, California, USA.
authors.forename: Alice
authors.initials: A
authors.lastname: Talpin
authors.affiliation: Rheumatology Division, Ambroise Paré Hospital (AP-HP), Boulogne-Billancourt, France.
authors.forename: Roula
authors.initials: R
authors.lastname: Said-Nahal
authors.affiliation: Rheumatology Division, Ambroise Paré Hospital (AP-HP), Boulogne-Billancourt, France.
authors.forename: Ariane
authors.initials: A
authors.lastname: Leboime
authors.affiliation: Faculty of Health Sciences Simone Veil, University of Versailles Saint-Quentin-en-Yvelines, Montigny-le-Bretonneux, France.|INSERM U1173 University of Versailles Saint-Quentin-en-Yvelines, Montigny-le-Bretonneux, France.|Université Paris Diderot, Sorbonne Paris Cité, Laboratoire d'Excellence, Paris, France.
authors.forename: Elena
authors.initials: E
authors.lastname: Zinovieva
authors.affiliation: National Genotyping Center (CNG), Evry, France.
authors.forename: Diana
authors.initials: D
authors.lastname: Zelenika
authors.affiliation: National Genotyping Center (CNG), Evry, France.
authors.forename: Ivo
authors.initials: I
authors.lastname: Gut
authors.affiliation: National Genotyping Center (CNG), Evry, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Charon
authors.affiliation: Faculty of Health Sciences Simone Veil, University of Versailles Saint-Quentin-en-Yvelines, Montigny-le-Bretonneux, France.|INSERM U1173 University of Versailles Saint-Quentin-en-Yvelines, Montigny-le-Bretonneux, France.|Université Paris Diderot, Sorbonne Paris Cité, Laboratoire d'Excellence, Paris, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Izac
authors.affiliation: Rheumatology Division, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Weissman
authors.affiliation: Faculty of Health Sciences Simone Veil, University of Versailles Saint-Quentin-en-Yvelines, Montigny-le-Bretonneux, France.|INSERM U1173 University of Versailles Saint-Quentin-en-Yvelines, Montigny-le-Bretonneux, France.|Université Paris Diderot, Sorbonne Paris Cité, Laboratoire d'Excellence, Paris, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Chiocchia
authors.affiliation: Department of Rheumatology and Clinical Immunogenetics, University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors.forename: John
authors.identifier: http://orcid.org/0000-0001-5950-0913
authors.initials: J
authors.lastname: Reveille
authors.affiliation: Faculty of Health Sciences Simone Veil, University of Versailles Saint-Quentin-en-Yvelines, Montigny-le-Bretonneux, France.|INSERM U1173 University of Versailles Saint-Quentin-en-Yvelines, Montigny-le-Bretonneux, France.|Université Paris Diderot, Sorbonne Paris Cité, Laboratoire d'Excellence, Paris, France.|Rheumatology Division, Ambroise Paré Hospital (AP-HP), Boulogne-Billancourt, France.
authors.forename: Maxime
authors.identifier: http://orcid.org/0000-0002-6932-9395
authors.initials: M
authors.lastname: Breban
authors.affiliation: Faculty of Health Sciences Simone Veil, University of Versailles Saint-Quentin-en-Yvelines, Montigny-le-Bretonneux, France.|INSERM U1173 University of Versailles Saint-Quentin-en-Yvelines, Montigny-le-Bretonneux, France.|Université Paris Diderot, Sorbonne Paris Cité, Laboratoire d'Excellence, Paris, France.|Genetics Division, Ambroise Paré Hospital (AP-HP), Boulogne-Billancourt, France.
authors.forename: Henri-Jean
authors.initials: HJ
authors.lastname: Garchon
mesh_terms: D000328:Adult; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D048308:Mitogen-Activated Protein Kinase 14 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D025241:Spondylarthritis / Q000235:genetics*
chemical_list: D048308:Mitogen-Activated Protein Kinase 14
keywords: Ankylosing Spondylitis; Gene Polymorphism; Spondyloarthritis