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Dense genotyping of immune-related susceptibility loci reveals new insights into the genetics of psoriatic arthritis

Author

Listed:
  • John Bowes

    (Arthritis Research UK Centre for Genetics and Genomics, The University of Manchester)

  • Ashley Budu-Aggrey

    (Arthritis Research UK Centre for Genetics and Genomics, The University of Manchester
    NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester Foundation Trust and University of Manchester, Manchester Academy of Health Sciences)

  • Ulrike Huffmeier

    (Institute of Human Genetics, University of Erlangen-Nuremberg)

  • Steffen Uebe

    (Institute of Human Genetics, University of Erlangen-Nuremberg)

  • Kathryn Steel

    (Arthritis Research UK Centre for Genetics and Genomics, The University of Manchester)

  • Harry L. Hebert

    (Arthritis Research UK Centre for Genetics and Genomics, The University of Manchester
    The Dermatology Centre, Salford Royal NHS Foundation Trust, University of Manchester, Manchester Academic Health Science Centre)

  • Chris Wallace

    (JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust/MRC Building, Cambridge Biomedical Campus
    Centre for Biostatistics, Institute of Population Health, The University of Manchester, Jean McFarlane Building)

  • Jonathan Massey

    (Arthritis Research UK Centre for Genetics and Genomics, The University of Manchester)

  • Ian N. Bruce

    (Arthritis Research UK Centre for Genetics and Genomics, The University of Manchester
    The Kellgren Centre for Rheumatology, Central Manchester Foundation Trust, NIHR Manchester Biomedical Research Centre)

  • James Bluett

    (Arthritis Research UK Centre for Genetics and Genomics, The University of Manchester
    The Kellgren Centre for Rheumatology, Central Manchester Foundation Trust, NIHR Manchester Biomedical Research Centre)

  • Marie Feletar

    (Monash University)

  • Ann W. Morgan

    (NIHR-Leeds Musculoskeletal Biomedical Research Unit, Leeds Institute of Molecular Medicine, University of Leeds)

  • Helena Marzo-Ortega

    (NIHR-Leeds Musculoskeletal Biomedical Research Unit, Leeds Institute of Molecular Medicine, University of Leeds)

  • Gary Donohoe

    (CogGene Group, Discipline of Biochemistry and School of Psychology, National University of Ireland)

  • Derek W. Morris

    (CogGene Group, Discipline of Biochemistry and School of Psychology, National University of Ireland)

  • Philip Helliwell

    (NIHR-Leeds Musculoskeletal Biomedical Research Unit, Leeds Institute of Molecular Medicine, University of Leeds)

  • Anthony W. Ryan

    (Institute of Molecular Medicine, Trinity College Dublin)

  • David Kane

    (Adelaide and Meath Hospital and Trinity College Dublin)

  • Richard B. Warren

    (The Dermatology Centre, Salford Royal NHS Foundation Trust, University of Manchester, Manchester Academic Health Science Centre)

  • Eleanor Korendowych

    (University of Bath)

  • Gerd-Marie Alenius

    (Rheumatology, University Hospital)

  • Emiliano Giardina

    (Centre of Excellence for Genomic Risk Assessment in Multifactorial and Complex Diseases, School of Medicine, University of Rome ‘Tor Vergata’ and Fondazione PTV ‘Policlinico Tor Vergata’)

  • Jonathan Packham

    (Haywood Hospital, Health Services Research Unit, Institute of Science and Technology in Medicine, Keele University)

  • Ross McManus

    (Institute of Molecular Medicine, Trinity College Dublin)

  • Oliver FitzGerald

    (St. Vincent’s University Hospital, UCD School of Medicine and Medical Sciences and Conway Institute of Biomolecular and Biomedical Research, University College Dublin)

  • Neil McHugh

    (University of Bath)

  • Matthew A. Brown

    (The University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital)

  • Pauline Ho

    (Arthritis Research UK Centre for Genetics and Genomics, The University of Manchester
    The Kellgren Centre for Rheumatology, Central Manchester Foundation Trust, NIHR Manchester Biomedical Research Centre)

  • Frank Behrens

    (Goethe University)

  • Harald Burkhardt

    (Goethe University)

  • Andre Reis

    (Institute of Human Genetics, University of Erlangen-Nuremberg)

  • Anne Barton

    (Arthritis Research UK Centre for Genetics and Genomics, The University of Manchester
    NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester Foundation Trust and University of Manchester, Manchester Academy of Health Sciences)

Abstract

Psoriatic arthritis (PsA) is a chronic inflammatory arthritis associated with psoriasis and, despite the larger estimated heritability for PsA, the majority of genetic susceptibility loci identified to date are shared with psoriasis. Here, we present results from a case–control association study on 1,962 PsA patients and 8,923 controls using the Immunochip genotyping array. We identify eight loci passing genome-wide significance, secondary independent effects at three loci and a distinct PsA-specific variant at the IL23R locus. We report two novel loci and evidence of a novel PsA-specific association at chromosome 5q31. Imputation of classical HLA alleles, amino acids and SNPs across the MHC region highlights three independent associations to class I genes. Finally, we find an enrichment of associated variants to markers of open chromatin in CD8+ memory primary T cells. This study identifies key insights into the genetics of PsA that could begin to explain fundamental differences between psoriasis and PsA.

Suggested Citation

  • John Bowes & Ashley Budu-Aggrey & Ulrike Huffmeier & Steffen Uebe & Kathryn Steel & Harry L. Hebert & Chris Wallace & Jonathan Massey & Ian N. Bruce & James Bluett & Marie Feletar & Ann W. Morgan & He, 2015. "Dense genotyping of immune-related susceptibility loci reveals new insights into the genetics of psoriatic arthritis," Nature Communications, Nature, vol. 6(1), pages 1-11, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7046
    DOI: 10.1038/ncomms7046
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    Cited by:

    1. Zhikai Wang & Yang Sun & Fangzhou Lou & Jing Bai & Hong Zhou & Xiaojie Cai & Libo Sun & Qianqian Yin & Sibei Tang & Yue Wu & Li Fan & Zhenyao Xu & Hong Wang & Xiaoyu Hu & Honglin Wang, 2022. "Targeting the transcription factor HES1 by L-menthol restores protein phosphatase 6 in keratinocytes in models of psoriasis," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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