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

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 22,64...

Full description

Bibliographic Details
Main 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, 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.
Format:	Online
Language:	English
Published:	Nature Pub. Group 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4443427/

id	pubmed-4443427
recordtype	oai_dc
spelling	pubmed-44434272015-06-18 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. Article 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. Nature Pub. Group 2015-05-21 /pmc/articles/PMC4443427/ /pubmed/25994336 http://dx.doi.org/10.1038/ncomms8146 Text en Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	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.
spellingShingle	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. Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1
author_facet	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.
author_sort	Cortes, Adrian
title	Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1
title_short	Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1
title_full	Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1
title_fullStr	Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1
title_full_unstemmed	Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1
title_sort	major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with erap1
description	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.
publisher	Nature Pub. Group
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4443427/
_version_	1613227470257913856

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

Similar Items