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

Bowes J, Budu-Aggrey A, Hüffmeier U, Uebe S, Steel K, Hebert HL, Wallace C, Massey J, Bruce IN, Bluett J, Feletar M, Morgan AW, Marzo-Ortega H, Donohoe G, Morris DW, Helliwell P, Ryan AW, Kane D, Warren RB, Korendowych E, Alenius GM, Giardina E, Packham J, Mcmanus R, Fitzgerald O, Mchugh N, Brown MA, Ho P, Behrens F, Burkhardt H, Reis A, Barton A (2015)

Publication Type: Journal article

Publication year: 2015

Journal

Nature Communications Nature Publishing Group: Nature Communications

Book Volume: 6

Pages Range: 6046

DOI: 10.1038/ncomms7046

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.

Authors with CRIS profile

Ulrike Hüffmeier Lehrstuhl für Humangenetik Steffen Uebe Institute of Human Genetics André Wiesmann da Silva Reis Lehrstuhl für Humangenetik

Involved external institutions

Goethe-Universität Frankfurt am Main DE Germany (DE) University of Manchester GB United Kingdom (GB) University of Queensland AU Australia (AU) University of Bath GB United Kingdom (GB) University College Dublin (UCD) IE Ireland (IE) Trinity College Dublin IE Ireland (IE) University of Keele GB United Kingdom (GB) Università degli Studi di Roma 'Tor Vergata' IT Italy (IT) University Hospital of Umeå / Norrlands universitetssjukhus (NUS) SE Sweden (SE) Adelaide and Meath Hospital IE Ireland (IE) University of Leeds GB United Kingdom (GB) National University of Ireland (NUI), Galway IE Ireland (IE) Monash University AU Australia (AU) University of Cambridge GB United Kingdom (GB)

How to cite

APA:

Bowes, J., Budu-Aggrey, A., Hüffmeier, U., Uebe, S., Steel, K., Hebert, H.L.,... Barton, A. (2015). Dense genotyping of immune-related susceptibility loci reveals new insights into the genetics of psoriatic arthritis. Nature Communications, 6, 6046. https://dx.doi.org/10.1038/ncomms7046

MLA:

Bowes, John, et al. "Dense genotyping of immune-related susceptibility loci reveals new insights into the genetics of psoriatic arthritis." Nature Communications 6 (2015): 6046.

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