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

2013; Nature Portfolio; Volume: 45; Issue: 7 Linguagem: Inglês

10.1038/ng.2667

1546-1718

Adrián Cortés, James L. Hadler, John Pointon, Philip C. Robinson, Tugce Karaderi, Paul Leo, Katie Cremin, Karena Pryce, Jessica Harris, S. Lee, Kyung Bin Joo, Seung Cheol Shim, Michael H. Weisman, Michael M. Ward, Xiaodong Zhou, Garchon Hj, Gilles Chiocchia, Johannes C. Nossent, B A Lie, Øystein Førre, Jaakko Tuomilehto, Kari Laiho, Lei Jiang, Y. Liu, Xinyu Wu, L Bradbury, Dirk Elewaut, Rubén Burgos‐Vargas, Simon Stebbings, Louise Appleton, Claire Farrah, Jonathan C. Lau, Tony Kenna, Nigil Haroon, Manuel A. R. Ferreira, Jian Yang, Juan Mulero, J.L. Fernández-Sueiro, Miguel Á. González‐Gay, Carlos López‐Larrea, Panos Deloukas, Peter Donnelly, Paul Bowness, Karl Gafney, Hill Gaston, Dafna D. Gladman, Proton Rahman, Walter P. Maksymowych, Huji Xu, Crusius Jba., Irene E. van der Horst‐Bruinsma, C-T. Chou, Raphael Valle-Oñate, Consuelo Romero‐Sánchez, Inger Myrnes Hansen, Fernando Pimentel-Santos, Robert D. Inman, Vibeke Videm, Javier Martı́n, Maxime Bréban, J. D. Reveille, David M. Evans, Kim T-H., B P Wordsworth, Matthew A. Brown,

Liver Diseases and Immunity

Matthew Brown and colleagues identify multiple susceptibility variants for ankylosing spondylitis through an association study based on high-density genotyping of immune-related loci. Their findings implicate numerous biological pathways in the pathogenesis of this disease and highlight shared risk factors with other autoimmune diseases. 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.