Dense genotyping of immune-related susceptibility loci reveals new insights into the genetics of psoriatic arthritis
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2015Access:
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Bowes, J. Budu-Aggrey, A. Huffmeier, U. Uebe, S. Steel, K. Hebert, H.L. Wallace, C. Massey, J. Bruce, I.N. Bluett, J. Feletar, M. Morgan, A.W. Marzo-Ortega, H. Donohoe, G. Morris, D.W. Helliwell, P. Ryan, A.W. Kane, D. Warren, R.B. Korendowych, E. Alenius, G.-M. Giardina, E. Packham, J. McManus, R. Fitzgerald, O. McHugh, N. Brown, M.A. Ho, P. Behrens, F. Burkhardt, H. Reis, A. Barton, A., Dense genotyping of immune-related susceptibility loci reveals new insights into the genetics of psoriatic arthritis, Nature Communications, 6, 2015, 6046-Download Item:
Abstract:
Poriatic 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
þ
memory primary Tcells. This study identifies key insights into the genetics
of PsA that could begin to explain fundamental differences between psoriasis and PsA.
Sponsor
Grant Number
Science Foundation Ireland (SFI)
Author's Homepage:
http://people.tcd.ie/rmcmanushttp://people.tcd.ie/kanedj
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PUBLISHED
Author: Mc Manus, Ross; Kane, David
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Nature Communications6
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Full text availableKeywords:
psoriatic arthritis (PsA)Subject (TCD):
Genes & Society , Immunology, Inflammation & InfectionDOI:
http://dx.doi.org/10.1038/ncomms7046Metadata
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