Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Outros Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | https://doi.org/10.1038/ncomms8146 |
Resumo: | 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. |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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7160 |
spelling |
Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1UNFOLDED PROTEIN RESPONSEGENOME-WIDE ASSOCIATIONSUSCEPTIBILITY LOCITRANSGENIC RATSENDOPLASMIC-RETICULUMBEHCETS-DISEASEHLA-B27HLAMHCANTIGENChemistry(all)Biochemistry, Genetics and Molecular Biology(all)Physics and Astronomy(all)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.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)Centro de Estudos de Doenças Crónicas (CEDOC)RUNCortes, AdrianPulit, Sara L.Leo, Paul J.Pointon, Jenny J.Robinson, Philip C.Weisman, Michael H.Ward, MichaelGensler, Lianne S.Zhou, XiaodongGarchon, Henri JeanChiocchia, GillesNossent, JohannesLie, Benedicte A.Førre, ØysteinTuomilehto, JaakkoLaiho, KariBradbury, Linda A.Elewaut, DirkBurgos-Vargas, RubenStebbings, SimonAppleton, LouiseFarrah, ClaireLau, JonathanHaroon, NigilMulero, JuanBlanco, Francisco J.Gonzalez-Gay, Miguel A.Lopez-Larrea, C.Bowness, PaulGaffney, KarlGaston, HillGladman, Dafna D.Rahman, ProtonMaksymowych, Walter P.Crusius, J. Bart AVan Der Horst-Bruinsma, Irene E.Valle-Oñate, RaphaelRomero-Sánchez, ConsueloHansen, Inger MyrnesPimentel-Santos, Fernando M.Inman, Robert D.Martin, JavierBreban, MaximeWordsworth, Bryan PaulReveille, John D.Evans, David M.De Bakker, Paul I WBrown, Matthew A.2017-09-18T22:03:15Z2015-05-212015-05-21T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article8application/pdfhttps://doi.org/10.1038/ncomms8146eng2041-1723PURE: 3137518http://www.scopus.com/inward/record.url?scp=84930216606&partnerID=8YFLogxKhttps://doi.org/10.1038/ncomms8146info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T04:11:36Zoai:run.unl.pt:10362/23365Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:27:46.369426Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1 |
title |
Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1 |
spellingShingle |
Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1 Cortes, Adrian UNFOLDED PROTEIN RESPONSE GENOME-WIDE ASSOCIATION SUSCEPTIBILITY LOCI TRANSGENIC RATS ENDOPLASMIC-RETICULUM BEHCETS-DISEASE HLA-B27 HLA MHC ANTIGEN Chemistry(all) Biochemistry, Genetics and Molecular Biology(all) Physics and Astronomy(all) |
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 |
author |
Cortes, Adrian |
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_role |
author |
author2 |
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. |
author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) Centro de Estudos de Doenças Crónicas (CEDOC) RUN |
dc.contributor.author.fl_str_mv |
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. |
dc.subject.por.fl_str_mv |
UNFOLDED PROTEIN RESPONSE GENOME-WIDE ASSOCIATION SUSCEPTIBILITY LOCI TRANSGENIC RATS ENDOPLASMIC-RETICULUM BEHCETS-DISEASE HLA-B27 HLA MHC ANTIGEN Chemistry(all) Biochemistry, Genetics and Molecular Biology(all) Physics and Astronomy(all) |
topic |
UNFOLDED PROTEIN RESPONSE GENOME-WIDE ASSOCIATION SUSCEPTIBILITY LOCI TRANSGENIC RATS ENDOPLASMIC-RETICULUM BEHCETS-DISEASE HLA-B27 HLA MHC ANTIGEN Chemistry(all) Biochemistry, Genetics and Molecular Biology(all) Physics and Astronomy(all) |
description |
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. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015-05-21 2015-05-21T00:00:00Z 2017-09-18T22:03:15Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://doi.org/10.1038/ncomms8146 |
url |
https://doi.org/10.1038/ncomms8146 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2041-1723 PURE: 3137518 http://www.scopus.com/inward/record.url?scp=84930216606&partnerID=8YFLogxK https://doi.org/10.1038/ncomms8146 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
8 application/pdf |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799137904983801856 |