International Genetics of Ankylosing Spondylitis Consortium (IGAS) None., Cortes A., Hadler J., Pointon JP., Robinson PC., Karaderi T., Leo P., Cremin K., Pryce K., Harris J., Lee S., Joo KB., Shim S-C., Weisman M., Ward M., Zhou X., Garchon H-J., Chiocchia G., Nossent J., Lie BA., Førre Ø., Tuomilehto J., Laiho K., Jiang L., Liu Y., Wu X., Bradbury LA., Elewaut D., Burgos-Vargas R., Stebbings S., Appleton L., Farrah C., Lau J., Kenna TJ., Haroon N., Ferreira MA., Yang J., Mulero J., Fernandez-Sueiro JL., Gonzalez-Gay MA., Lopez-Larrea C., Deloukas P., Donnelly P., Australo-Anglo-American Spondyloarthritis Consortium (TASC) None., Groupe Française d'Etude Génétique des Spondylarthrites (GFEGS) None., Nord-Trøndelag Health Study (HUNT) None., Spondyloarthritis Research Consortium of Canada (SPARCC) None., Wellcome Trust Case Control Consortium 2 (WTCCC2) None., Bowness P., Gafney K., Gaston H., Gladman DD., Rahman P., Maksymowych WP., Xu H., Crusius JBA., van der Horst-Bruinsma IE., Chou C-T., Valle-Oñate R., Romero-Sánchez C., Hansen IM., Pimentel-Santos FM., Inman RD., Videm V., Martin J., Breban M., Reveille JD., Evans DM., Kim T-H., Wordsworth BP., Brown MA.

Ankylosing spondylitis is a common, highly heritable inflammatory arthritis affecting primarily the spine and pelvis. In addition to HLA-B*27 alleles, 12 loci have previously been identified that are associated with ankylosing spondylitis in populations of European ancestry, and 2 associated loci have been identified in Asians. In this study, we used the Illumina Immunochip microarray to perform a case-control association study involving 10,619 individuals with ankylosing spondylitis (cases) and 15,145 controls. We identified 13 new risk loci and 12 additional ankylosing spondylitis-associated haplotypes at 11 loci. Two ankylosing spondylitis-associated regions have now been identified encoding four aminopeptidases that are involved in peptide processing before major histocompatibility complex (MHC) class I presentation. Protective variants at two of these loci are associated both with reduced aminopeptidase function and with MHC class I cell surface expression.

Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci.

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