Author:
Bowes John,Budu-Aggrey Ashley,Huffmeier Ulrike,Uebe Steffen,Steel Kathryn,Hebert Harry L.,Wallace Chris,Massey Jonathan,Bruce Ian N.,Bluett James,Feletar Marie,Morgan Ann W.,Marzo-Ortega Helena,Donohoe Gary,Morris Derek W.,Helliwell Philip,Ryan Anthony W.,Kane David,Warren Richard B.,Korendowych Eleanor,Alenius Gerd-Marie,Giardina Emiliano,Packham Jonathan,McManus Ross,FitzGerald Oliver,McHugh Neil,Brown Matthew A.,Ho Pauline,Behrens Frank,Burkhardt Harald,Reis Andre,Barton Anne
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.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry
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