Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1

Cortes, Adrian, Pulit, Sara L., Leo, Paul J., Pointon, Jenny J., Robinson, Philip C., Weisman, Michael H., Ward, Michael, Gensler, Lianne S., Zhou, Xiaodong, Garchon, Henri-Jean, Chiocchia, Gilles, Nossent, Johannes, Lie, Benedicte A., Førre, Øystein, Tuomilehto, Jaakko, Laiho, Kari, Bradbury, Linda A., Elewaut, Dirk, Burgos-Vargas, Ruben, Stebbings, Simon, Appleton, Louise, Farrah, Claire, Lau, Jonathan, Haroon, Nigil, Mulero, Juan, Blanco, Francisco J., Gonzalez-Gay, Miguel A., Lopez-Larrea, C, Bowness, Paul, Gaffney, Karl, Gaston, Hill, Gladman, Dafna D., Rahman, Proton, Maksymowych, Walter P., Crusius, J. Bart A., van der Horst-Bruinsma, Irene E., Valle-Oñate, Raphael, Romero-Sánchez, Consuelo, Hansen, Inger Myrnes, Pimentel-Santos, Fernando M., Inman, Robert D., Martin, Javier, Breban, Maxime, Wordsworth, Bryan Paul, Reveille, John D., Evans, David M., de Bakker, Paul I.W., & Brown, Matthew A. (2015) Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1. Nature Communications, 6(May), Article number: 7146.

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Abstract

Ankylosing spondylitis (AS) is a common, highly heritable, inflammatory arthritis for which HLA-B27 is the major genetic risk factor, although its role in the aetiology of AS remains elusive. To better understand the genetic basis of the MHC susceptibility loci, we genotyped 7,264 MHC SNPs in 22,647 AS cases and controls of European descent. We impute SNPs, classical HLA alleles and amino-acid residues within HLA proteins, and tested these for association to AS status. Here we show that in addition to effects due to HLA-B27 alleles, several other HLA-B alleles also affect susceptibility. After controlling for the associated haplotypes in HLA-B, we observe independent associations with variants in the HLA-A, HLA-DPB1 and HLA-DRB1 loci. We also demonstrate that the ERAP1 SNP rs30187 association is not restricted only to carriers of HLA-B27 but also found in HLA-B40:01 carriers independently of HLA-B*27 genotype.

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ID Code: 89170
Item Type: Journal Article
Refereed: Yes
DOI: 10.1038/ncomms8146
ISSN: 2041-1723
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2015 Macmillan Publishers Limited
Deposited On: 15 Oct 2015 04:15
Last Modified: 16 Feb 2016 02:22

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