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Nat Commun. 2015 Feb 5;6:6046. doi: 10.1038/ncomms7046.

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

Author information

1
Arthritis Research UK Centre for Genetics and Genomics, The University of Manchester, Manchester M13 9PT, UK.
2
1] Arthritis Research UK Centre for Genetics and Genomics, The University of Manchester, Manchester M13 9PT, UK [2] NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester Foundation Trust and University of Manchester, Manchester Academy of Health Sciences, Manchester M13 9WU, UK.
3
Institute of Human Genetics, University of Erlangen-Nuremberg, Erlangen 91054, Germany.
4
1] Arthritis Research UK Centre for Genetics and Genomics, The University of Manchester, Manchester M13 9PT, UK [2] The Dermatology Centre, Salford Royal NHS Foundation Trust, University of Manchester, Manchester Academic Health Science Centre, Manchester M6 8HD, UK.
5
1] JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK [2] Centre for Biostatistics, Institute of Population Health, The University of Manchester, Jean McFarlane Building, Oxford Road, Manchester M13 9PL, UK.
6
1] Arthritis Research UK Centre for Genetics and Genomics, The University of Manchester, Manchester M13 9PT, UK [2] The Kellgren Centre for Rheumatology, Central Manchester Foundation Trust, NIHR Manchester Biomedical Research Centre, Manchester M13 9WL, UK.
7
Monash University, Melbourne, Victoria 3800, Australia.
8
NIHR-Leeds Musculoskeletal Biomedical Research Unit, Leeds Institute of Molecular Medicine, University of Leeds, Leeds LS7 4SA, UK.
9
CogGene Group, Discipline of Biochemistry and School of Psychology, National University of Ireland, Galway, Ireland.
10
Department of Clinical Medicine, Institute of Molecular Medicine, Trinity College Dublin, Dublin 8, Ireland.
11
Adelaide and Meath Hospital and Trinity College Dublin, Dublin 24, Ireland.
12
The Dermatology Centre, Salford Royal NHS Foundation Trust, University of Manchester, Manchester Academic Health Science Centre, Manchester M6 8HD, UK.
13
Royal National Hospital for Rheumatic Diseases and Department of Pharmacy and Pharmacology, University of Bath, Bath BA1 1RL, UK.
14
Department of Public Health and Clinical Medicine, Rheumatology, University Hospital, Umeå 901 87, Sweden.
15
Department of Biopathology, 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', Rome 18-00173, Italy.
16
Rheumatology Department, Haywood Hospital, Health Services Research Unit, Institute of Science and Technology in Medicine, Keele University, Keele ST5 5BG, UK.
17
Department of Rheumatology, St. Vincent's University Hospital, UCD School of Medicine and Medical Sciences and Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin 4, Ireland.
18
The University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Brisbane, Queensland QLD 4102, Australia.
19
Division of Rheumatology and Fraunhofer IME-Project-Group Translational Medicine and Pharmacology, Goethe University, Frankfurt 60590, Germany.

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.

PMID:
25651891
PMCID:
PMC4327416
DOI:
10.1038/ncomms7046
[Indexed for MEDLINE]
Free PMC Article

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