title: The histone demethylase JARID1A is associated with susceptibility to ankylosing spondylitis.
abstract: Associations with disease identified by genome-wide association studies (GWAS) must be replicated and refined to validate causative variants. In the Wellcome Trust Case Control Consortium (WTCCC) GWAS using 14 500 non-synonymous single nucleotide polymorphisms (nsSNP), rs11062385 (a nsSNP in JARID1A) showed nominal association with ankylosing spondylitis (AS) (P=0.0006, odds ratio (OR)=1.26, 95% confidence interval (95% CI)=1.1-1.4). To replicate and refine the association of JARID1A, rs11062385 was genotyped in 730 further cases and compared with allele frequencies in non-AS disease cohorts typed by WTCCC. We replicated the initial association (P=0.04, OR=1.16, 95% CI=1.01-1.34) and identified a strengthened association with AS in a meta-analysis of this new study combined with the original WTCCC study (P=0.0001, OR=1.21, 95% CI=1.10-1.33). We also genotyped nine further intronic tagging SNPs in JARID1A in 1604 AS cases and 1020 new control samples, but none was associated with AS. JARID1A or a locus in strong linkage disequilibrium with it is a positional candidate for susceptibility to AS.
authors.affiliation: National Institute for Health Research Oxford Musculoskeletal Biomedical Research Unit and Botnar Research Centre, Nuffield Orthopaedic Centre, Oxford, UK. jenny.pointon@ndorms.ox.ac.uk
authors.forename: J J
authors.initials: JJ
authors.lastname: Pointon
authors.forename: D
authors.initials: D
authors.lastname: Harvey
authors.forename: T
authors.initials: T
authors.lastname: Karaderi
authors.forename: L H
authors.initials: LH
authors.lastname: Appleton
authors.forename: C
authors.initials: C
authors.lastname: Farrar
authors.forename: B P
authors.initials: BP
authors.lastname: Wordsworth
mesh_terms: D016022:Case-Control Studies; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D056466:Histone Demethylases / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D056485:Retinoblastoma-Binding Protein 2 / Q000235:genetics* / Q000378:metabolism; D013167:Spondylitis, Ankylosing / Q000201:enzymology / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D056466:Histone Demethylases; C070050:KDM5A protein, human; D056485:Retinoblastoma-Binding Protein 2