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

Research output: Contribution to journalJournal articleResearchpeer-review

  • Adrian Cortes
  • Johanna Hadler
  • Jenny P. Pointon
  • Philip C. Robinson
  • Paul Leo
  • Katie Cremin
  • Karena Pryce
  • Jessica Harris
  • Seunghun Lee
  • Kyung Bin Joo
  • Seung Cheol Shim
  • Michael Weisman
  • Michael Ward
  • Xiaodong Zhou
  • Henri Jean Garchon
  • Gilles Chiocchia
  • Johannes Nossent
  • Benedicte A. Lie
  • Øystein Førre
  • Jaakko Tuomilehto
  • Kari Laiho
  • Lei Jiang
  • Xin Wu
  • Linda A. Bradbury
  • Dirk Elewaut
  • Ruben Burgos-Vargas
  • Simon Stebbings
  • Louise Appleton
  • Claire Farrah
  • Jonathan Lau
  • Tony J. Kenna
  • Nigil Haroon
  • Manuel A. Ferreira
  • Jian Yang
  • Juan Mulero
  • Jose Luis Fernandez-Sueiro
  • Miguel A. Gonzalez-Gay
  • Carlos Lopez-Larrea
  • Panos Deloukas
  • Peter Donnelly
  • Paul Bowness
  • Karl Gafney
  • Hill Gaston
  • Dafna D. Gladman
  • Proton Rahman
  • Walter P. Maksymowych
  • Huji Xu
  • J. Bart A. Crusius

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.

Original languageEnglish
JournalNature Genetics
Volume45
Issue number7
Pages (from-to)730-738
Number of pages9
ISSN1061-4036
DOIs
Publication statusPublished - 1 Jul 2013
Externally publishedYes

ID: 226396293