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

Nat Genet. 2013 Jul;45(7):730-8. doi: 10.1038/ng.2667. Epub 2013 Jun 9.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Case-Control Studies
  • DNA Mutational Analysis / methods
  • Genetic Loci* / immunology
  • Genetic Predisposition to Disease / ethnology
  • Genetic Predisposition to Disease / genetics*
  • Genome-Wide Association Study / methods
  • Genotype
  • Genotyping Techniques / methods
  • HLA-B27 Antigen / genetics
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Immune System Phenomena / genetics*
  • Polymorphism, Single Nucleotide*
  • Risk Factors
  • Spondylitis, Ankylosing / ethnology
  • Spondylitis, Ankylosing / genetics*
  • Spondylitis, Ankylosing / immunology

Substances

  • HLA-B27 Antigen