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

  • 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.

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Author:John Bowes, Ashley Budu-Aggrey, Ulrike Huffmeier, Steffen UebeORCiDGND, 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 BehrensORCiDGND, Harald BurkhardtORCiDGND, Andre ReisORCiDGND, Anne Barton
URN:urn:nbn:de:hebis:30:3-393833
DOI:https://doi.org/10.1038/ncomms7046
ISSN:2041-1723
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/25651891
Parent Title (English):Nature Communications
Publisher:Nature Publishing Group
Place of publication:London
Document Type:Article
Language:English
Date of Publication (online):2015/02/05
Date of first Publication:2015/02/05
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2016/02/04
Volume:6
Issue:6046
Page Number:10
First Page:1
Last Page:10
Note:
This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
HeBIS-PPN:377939552
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0