title: Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci.
abstract: 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.
authors.affiliation: University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia.
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authors.lastname: Lopez-Larrea
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authors.lastname: Deloukas
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authors.lastname: Gafney
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authors.lastname: Gladman
authors.forename: Proton
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authors.lastname: Rahman
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authors.lastname: Maksymowych
authors.forename: Huji
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authors.lastname: Xu
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authors.lastname: Crusius
authors.forename: Irene E
authors.initials: IE
authors.lastname: van der Horst-Bruinsma
authors.forename: Chung-Tei
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authors.lastname: Valle-Oñate
authors.forename: Consuelo
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authors.lastname: Romero-Sánchez
authors.forename: Inger Myrnes
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authors.lastname: Hansen
authors.forename: Fernando M
authors.initials: FM
authors.lastname: Pimentel-Santos
authors.forename: Robert D
authors.initials: RD
authors.lastname: Inman
authors.forename: Vibeke
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authors.lastname: Videm
authors.forename: Javier
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authors.lastname: Martin
authors.forename: Maxime
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authors.lastname: Breban
authors.forename: John D
authors.initials: JD
authors.lastname: Reveille
authors.forename: David M
authors.initials: DM
authors.lastname: Evans
authors.forename: Tae-Hwan
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authors.lastname: Kim
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authors.lastname: Wordsworth
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authors.lastname: Brown
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D004252:DNA Mutational Analysis / Q000379:methods; D056426:Genetic Loci / Q000276:immunology; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D060005:Genotyping Techniques / Q000379:methods; D015796:HLA-B27 Antigen / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D055633:Immune System Phenomena / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013167:Spondylitis, Ankylosing / Q000208:ethnology / Q000235:genetics* / Q000276:immunology
chemical_list: D015796:HLA-B27 Antigen