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

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Abstract
Ankylosing spondylitis (AS) is a common, highly heritable, inflammatory arthritis for which HLA-B*27 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-B*27 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-B*27 but also found in HLA-B*40:01 carriers independently of HLA-B*27 genotype.
Keywords
HLA-B27, BEHCETS-DISEASE, ENDOPLASMIC-RETICULUM, TRANSGENIC RATS, HLA, UNFOLDED PROTEIN RESPONSE, SUSCEPTIBILITY LOCI, ANTIGEN, MHC, GENOME-WIDE ASSOCIATION

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MLA
Cortes, Adrian et al. “Major Histocompatibility Complex Associations of Ankylosing Spondylitis Are Complex and Involve Further Epistasis with ERAP1.” NATURE COMMUNICATIONS 6 (2015): n. pag. Print.
APA
Cortes, A., Pulit, S. L., Leo, P. J., Pointon, J. J., Robinson, P. C., Weisman, M. H., Ward, M., et al. (2015). Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1. NATURE COMMUNICATIONS, 6.
Chicago author-date
Cortes, Adrian, Sara L Pulit, Paul J Leo, Jenny J Pointon, Philip C Robinson, Michael H Weisman, Michael Ward, et al. 2015. “Major Histocompatibility Complex Associations of Ankylosing Spondylitis Are Complex and Involve Further Epistasis with ERAP1.” Nature Communications 6.
Chicago author-date (all authors)
Cortes, Adrian, Sara L Pulit, Paul J Leo, Jenny J Pointon, Philip C Robinson, Michael H Weisman, Michael Ward, Lianne S Gensler, Xiaodong Zhou, Henri-Jean Garchon, Gilles Chiocchia, Johannes Nossent, Benedicte A Lie, Øystein Forre, Jaakko Tuomilehto, Kari Laiho, Linda A Bradbury, Dirk Elewaut, Ruben Burgos-Vargas, Simon Stebbings, Louise Appleton, Claire Farrah, Jonathan Lau, Nigil Haroon, Juan Mulero, Francisco J Blanco, Miguel A Gonzalez-Gay, C Lopez-Larrea, Paul Bowness, Karl Gaffney, Hill Gaston, Dafna D Gladman, Proton Rahman, Walter P Maksymowych, J Bart A Crusius, Irene E van der Horst-Bruinsma, Raphael Valle-Onate, Consuelo Romero-Sánchez, Inger Myrnes Hansen, Fernanco M Pimentel-Santos, Robert D Inman, Javier Martin, Maxime Breban, Bryan Paul Wordsworth, John D Reveille, David M Evans, Paul IW de Bakker, and Matthew A Brown. 2015. “Major Histocompatibility Complex Associations of Ankylosing Spondylitis Are Complex and Involve Further Epistasis with ERAP1.” Nature Communications 6.
Vancouver
1.
Cortes A, Pulit SL, Leo PJ, Pointon JJ, Robinson PC, Weisman MH, et al. Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1. NATURE COMMUNICATIONS. 2015;6.
IEEE
[1]
A. Cortes et al., “Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1,” NATURE COMMUNICATIONS, vol. 6, 2015.
@article{6887791,
  abstract     = {Ankylosing spondylitis (AS) is a common, highly heritable, inflammatory arthritis for which HLA-B*27 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-B*27 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-B*27 but also found in HLA-B*40:01 carriers independently of HLA-B*27 genotype.},
  articleno    = {7146},
  author       = {Cortes, Adrian and Pulit, Sara L and Leo, Paul J and Pointon, Jenny J and Robinson, Philip C and Weisman, Michael H and Ward, Michael and Gensler, Lianne S and Zhou, Xiaodong and Garchon, Henri-Jean and Chiocchia, Gilles and Nossent, Johannes and Lie, Benedicte A and Forre, Øystein and Tuomilehto, Jaakko and Laiho, Kari and Bradbury, Linda A and Elewaut, Dirk and Burgos-Vargas, Ruben and Stebbings, Simon and Appleton, Louise and Farrah, Claire and Lau, Jonathan and Haroon, Nigil and Mulero, Juan and Blanco, Francisco J and Gonzalez-Gay, Miguel A and Lopez-Larrea, C and Bowness, Paul and Gaffney, Karl and Gaston, Hill and Gladman, Dafna D and Rahman, Proton and Maksymowych, Walter P and Crusius, J Bart A and van der Horst-Bruinsma, Irene E and Valle-Onate, Raphael and Romero-Sánchez, Consuelo and Hansen, Inger Myrnes and Pimentel-Santos, Fernanco M and Inman, Robert D and Martin, Javier and Breban, Maxime and Wordsworth, Bryan Paul and Reveille, John D and Evans, David M and de Bakker, Paul IW and Brown, Matthew A},
  issn         = {2041-1723},
  journal      = {NATURE COMMUNICATIONS},
  keywords     = {HLA-B27,BEHCETS-DISEASE,ENDOPLASMIC-RETICULUM,TRANSGENIC RATS,HLA,UNFOLDED PROTEIN RESPONSE,SUSCEPTIBILITY LOCI,ANTIGEN,MHC,GENOME-WIDE ASSOCIATION},
  language     = {eng},
  pages        = {8},
  title        = {Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1},
  url          = {http://dx.doi.org/10.1038/ncomms8146},
  volume       = {6},
  year         = {2015},
}

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