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

doi:10.1038/ncomms8146

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

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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, …

Nature communications, Vol.6(1), pp.7146-7146

21/05/2015

DOI: https://doi.org/10.1038/ncomms8146

PMCID: PMC4443427

PMID: 25994336

Abstract

Aminopeptidases - genetics

Case-Control Studies

Epistasis, Genetic

Genetic Predisposition to Disease

HLA-B27 Antigen - genetics

HLA-B40 Antigen - genetics

Humans

Major Histocompatibility Complex

Minor Histocompatibility Antigens

Polymorphism, Single Nucleotide

Spondylitis, Ankylosing - etiology

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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Title: Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1
Creators - without role: Adrian Cortes - Princess Alexandra Hospital
Sara L Pulit - University Medical Center Utrecht
Paul J Leo - Princess Alexandra Hospital
Jenny J Pointon - Nuffield Orthopaedic Centre
Philip C Robinson - Princess Alexandra Hospital
Michael H Weisman - Cedars-Sinai Medical Center
Michael Ward - National Institute of Arthritis and Musculoskeletal and Skin Diseases
Lianne S Gensler - University of California, San Francisco
Xiaodong Zhou - The University of Texas Health Science Center at Houston
Henri-Jean Garchon - Inserm
Gilles Chiocchia - Université de Versailles Saint-Quentin-en-Yvelines
Johannes Nossent - Sir Charles Gairdner Hospital
Benedicte A Lie - Oslo University Hospital
Øystein Førre - Oslo University Hospital
Jaakko Tuomilehto - King Abdulaziz University
Kari Laiho - Päijät-Hämeen Keskussairaala
Linda A Bradbury - Princess Alexandra Hospital
Dirk Elewaut - Ghent University Hospital
Ruben Burgos-Vargas - Hospital General de México
Simon Stebbings - University of Otago
Louise Appleton - Nuffield Orthopaedic Centre
Claire Farrah - Nuffield Orthopaedic Centre
Jonathan Lau - Nuffield Orthopaedic Centre
Nigil Haroon - Toronto Western Hospital
Juan Mulero - Hospital Universitario Puerta de Hierro Majadahonda
Francisco J Blanco - Complexo Hospitalario Universitario A Coruña
Miguel A Gonzalez-Gay - Fundación Marques de Valdecilla
C Lopez-Larrea - Central University Hospital of Asturias
Paul Bowness - Nuffield Orthopaedic Centre
Karl Gaffney - Norfolk and Norwich University Hospital
Hill Gaston - University of Cambridge
Dafna D Gladman - University of Toronto
Proton Rahman - Memorial University of Newfoundland
Walter P Maksymowych - University of Alberta
J Bart A Crusius - Amsterdam UMC Location VUmc
Irene E van der Horst-Bruinsma - Amsterdam UMC Location VUmc
Raphael Valle-Oñate - Hospital Militar Central
Consuelo Romero-Sánchez - Universidad de La Sabana
Inger Myrnes Hansen - Helgelandssykehuset, 8613 Mo i Rana, Norway
Fernando M Pimentel-Santos - Universidade Nova de Lisboa
Robert D Inman - Toronto Western Hospital
Javier Martin - Instituto de Parasitología y Biomedicina "López - Neyra"
Maxime Breban - Université de Versailles Saint-Quentin-en-Yvelines
Bryan Paul Wordsworth - Nuffield Orthopaedic Centre
John D Reveille - The University of Texas Health Science Center at Houston
David M Evans - University of Bristol
Paul I W de Bakker - University Medical Center Utrecht
Matthew A Brown - University of Queensland
Publication Details: Nature communications, Vol.6(1), pp.7146-7146
Grant note: 20796 / Arthritis Research UK 20796 / Versus Arthritis P01 AR052915 / NIAMS NIH HHS 1R01AR062886-1 / NIAMS NIH HHS 19356 / Arthritis Research UK 19356 / Versus Arthritis 084767 / Wellcome Trust 19536 / Arthritis Research UK 18797 / Arthritis Research UK Intramural NIH HHS 1U01AI09090-01 / NIAID NIH HHS R01 AR062886 / NIAMS NIH HHS MC_UU_12013/4 / Medical Research Council
Identifiers: 9938318208331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article