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

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, Helena Marzo-Ortega, Gary Donohoe, Derek W. Morris, Philip Helliwell, Anthony W. Ryan, David Kane, Richard B. Warren, Eleanor Korendowych, Gerd-Marie Alenius, Emiliano Giardina, Jonathan Packham, Ross McManus, Oliver FitzGerald, Neil McHugh, Matthew A. Brown, Pauline Ho, Frank Behrens, Harald Burkhardt, Andre Reis and Anne Barton ()
Additional contact information
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
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
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
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
James Bluett: Arthritis Research UK Centre for Genetics and Genomics, The University of Manchester
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
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

Nature Communications, 2015, vol. 6, issue 1, 1-11

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms7046

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