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

Author

Listed:
  • Adrian Cortes

    (University of Queensland Diamantina Institute, Princess Alexandra Hospital)

  • Sara L. Pulit

    (Center for Molecular Medicine, University Medical Center Utrecht)

  • Paul J. Leo

    (University of Queensland Diamantina Institute, Princess Alexandra Hospital)

  • Jenny J. Pointon

    (NIHR Oxford Musculoskeletal Biomedical Research Unit, Nuffield Orthopaedic Centre)

  • Philip C. Robinson

    (University of Queensland Diamantina Institute, Princess Alexandra Hospital)

  • Michael H. Weisman

    (Cedars-Sinai Medical Center)

  • Michael Ward

    (Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health)

  • Lianne S. Gensler

    (University of California)

  • Xiaodong Zhou

    (University of Texas Health Science Center at Houston)

  • Henri-Jean Garchon

    (INSERM UMR 1173, Université de Versailles Saint Quentin en Yvelines, Laboratoire d’excellence Inflamex
    Hôpital Ambroise Paré, AP-HP, and Université de Versailles Saint Quentin en Yvelines)

  • Gilles Chiocchia

    (INSERM UMR 1173, Université de Versailles Saint Quentin en Yvelines, Laboratoire d’excellence Inflamex)

  • Johannes Nossent

    (School of Medicine, University of Western Australia
    Sir Charles Gairdner Hospital)

  • Benedicte A. Lie

    (University of Oslo and Oslo University Hospital
    Oslo University Hospital)

  • Øystein Førre

    (Oslo University Hospital, and University of Oslo)

  • Jaakko Tuomilehto

    (National Institute for Health and Welfare
    Centre for Vascular Prevention, Danube-University Krems
    Diabetes Research Group, King Abdulaziz University)

  • Kari Laiho

    (Paijat-Hame Central Hospital)

  • Linda A. Bradbury

    (University of Queensland Diamantina Institute, Princess Alexandra Hospital)

  • Dirk Elewaut

    (Gent University Hospital
    VIB Inflammation Research Center, Ghent University)

  • Ruben Burgos-Vargas

    (Hospital General de Mexico and Universidad Nacional Autonoma de Mexico)

  • Simon Stebbings

    (Dunedin School of Medicine, University of Otago)

  • Louise Appleton

    (NIHR Oxford Musculoskeletal Biomedical Research Unit, Nuffield Orthopaedic Centre)

  • Claire Farrah

    (NIHR Oxford Musculoskeletal Biomedical Research Unit, Nuffield Orthopaedic Centre)

  • Jonathan Lau

    (NIHR Oxford Musculoskeletal Biomedical Research Unit, Nuffield Orthopaedic Centre)

  • Nigil Haroon

    (Toronto Western Hospital, University of Toronto)

  • Juan Mulero

    (Hospital Puerta de Hierro)

  • Francisco J. Blanco

    (Complejo Hospitalario La Coruña, INIBIC)

  • Miguel A. Gonzalez-Gay

    (Hospital Marques de Valcecillas, IFIMAV)

  • C Lopez-Larrea

    (Hospital Universitario Central de Asturias
    Fundación Renal ‘Iñigo Álvarez de Toledo’)

  • Paul Bowness

    (NIHR Oxford Musculoskeletal Biomedical Research Unit, Nuffield Orthopaedic Centre)

  • Karl Gaffney

    (Norfolk and Norwich University Hospital)

  • Hill Gaston

    (University of Cambridge, Addenbrookes Hospital)

  • Dafna D. Gladman

    (University of Toronto
    Toronto Western Research Institute
    Psoriatic Arthritis Program, University Health Network, Toronto ON M4N 3M5, Canada)

  • Proton Rahman

    (Memorial University of Newfoundland)

  • Walter P. Maksymowych

    (University of Alberta)

  • J. Bart A. Crusius

    (Laboratory of Immunogenetics, VU University Medical Center)

  • Irene E. van der Horst-Bruinsma

    (VU University Medical Centre)

  • Raphael Valle-Oñate

    (Hospital Militar Central/Universidad de La Sabana)

  • Consuelo Romero-Sánchez

    (Hospital Militar Central/Universidad de La Sabana)

  • Inger Myrnes Hansen

    (Helgelandssykehuset, 8613)

  • Fernando M. Pimentel-Santos

    (Chronic Diseases Research Centre (CEDOC), Faculdade de Ciências Médicas, Universidade Nova de Lisboa)

  • Robert D. Inman

    (Toronto Western Hospital, University of Toronto)

  • Javier Martin

    (Instituto de Parasitología y Biomedicina López-Neyra, Consejo Superior de Investigaciones–Científicas)

  • Maxime Breban

    (INSERM UMR 1173, Université de Versailles Saint Quentin en Yvelines, Laboratoire d’excellence Inflamex
    Hôpital Ambroise Paré, AP-HP, and Université de Versailles Saint Quentin en Yvelines)

  • Bryan Paul Wordsworth

    (NIHR Oxford Musculoskeletal Biomedical Research Unit, Nuffield Orthopaedic Centre)

  • John D. Reveille

    (University of Texas Health Science Center at Houston)

  • David M. Evans

    (University of Queensland Diamantina Institute, Princess Alexandra Hospital
    MRC Integrative Epidemiology Unit, University of Bristol
    School of Social and Community Medicine, University of Bristol)

  • Paul I.W. de Bakker

    (Center for Molecular Medicine, University Medical Center Utrecht
    Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht)

  • Matthew A. Brown

    (University of Queensland Diamantina Institute, Princess Alexandra Hospital)

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.

Suggested Citation

  • 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 & Jo, 2015. "Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1," Nature Communications, Nature, vol. 6(1), pages 1-8, November.
  • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8146
    DOI: 10.1038/ncomms8146
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    Cited by:

    1. Sarah E. Garnish & Katherine R. Martin & Maria Kauppi & Victoria E. Jackson & Rebecca Ambrose & Vik Ven Eng & Shene Chiou & Yanxiang Meng & Daniel Frank & Emma C. Tovey Crutchfield & Komal M. Patel & , 2023. "A common human MLKL polymorphism confers resistance to negative regulation by phosphorylation," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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