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.; Øystein, Førre; Tuomilehto, Jaakko; Laiho, Kari; Bradbury, Linda A.; Elewaut, Dirk; Burgos-Vargas, Rubén; Stebbings, Simon; Appleton, Louise; Farrah, Claire; Lau, Jonathan; Haroon, Nigil; Mulero, Juan; Blanco García, Francisco J; González-Gay, Miguel Á.; López-Larrea, Carlos; Bowness, Paul; Gaffney, Karl; Gaston, Hill; Gladman, Dafna D.; Rahman, Proton; Maksymowych, Walter P.; Crusius, Bart A.; van der Horst-Buinsma, Irene E.; Valle-Oñate, Raphael; Romero-Sánchez, Consuelo; Hansen, Inger Myrnes; Pimentel-Santos, Fernando M.; Inman, Robert D.; Martín, Javier; Breban, Maxime; Wordsworth, Bryan Paul; Reveille, John D.; Evans, David M.; Bakker, Paul I.W. de; Brown, Matthew A.

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http://hdl.handle.net/2183/25300

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

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Identifiers

URI: http://hdl.handle.net/2183/25300

Publication date

2015-05-21

Authors

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

Bibliographic citation

Cortes A, Pulit SL, Leo PJ, Pointon JJ, Robinson PC, Weisman MH, Ward M, Gensler LS, Zhou X, Garchon HJ, Chiocchia G, Nossent J, Lie BA, Førre Ø, Tuomilehto J, Laiho K, Bradbury LA, Elewaut D, Burgos-Vargas R, Stebbings S, Appleton L, Farrah C, Lau J, Haroon N, Mulero J, Blanco FJ, Gonzalez-Gay MA, Lopez-Larrea C, Bowness P, Gaffney K, Gaston H, Gladman DD, Rahman P, Maksymowych WP, Crusius JB, van der Horst-Bruinsma IE, Valle-Oñate R, Romero-Sánchez C, Hansen IM, Pimentel-Santos FM, Inman RD, Martin J, Breban M, Wordsworth BP, Reveille JD, Evans DM, de Bakker PI, Brown MA. Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1. Nat Commun. 2015 May 21;6:7146.

Abstract

[Abstract] Article Open Access Published: 21 May 2015 Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1 Adrian Cortes, 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 Førre, 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-Oñate, Consuelo Romero-Sánchez, Inger Myrnes Hansen, Fernando M. Pimentel-Santos, Robert D. Inman, Javier Martin, Maxime Breban, Bryan Paul Wordsworth, John D. Reveille, David M. Evans, Paul I.W. de Bakker & Matthew A. Brown - Show fewer authors Nature Communications volume 6, Article number: 7146 (2015) Cite this article 1320 Accesses 97 Citations 2 Altmetric Metricsdetails 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.