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Nat Genet. 2010 Nov;42(11):985-90. doi: 10.1038/ng.694. Epub 2010 Oct 17.

A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1.

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1
Wellcome Trust Centre for Human Genetics, Oxford, UK.

Abstract

To identify new susceptibility loci for psoriasis, we undertook a genome-wide association study of 594,224 SNPs in 2,622 individuals with psoriasis and 5,667 controls. We identified associations at eight previously unreported genomic loci. Seven loci harbored genes with recognized immune functions (IL28RA, REL, IFIH1, ERAP1, TRAF3IP2, NFKBIA and TYK2). These associations were replicated in 9,079 European samples (six loci with a combined P < 5 × 10⁻⁸ and two loci with a combined P < 5 × 10⁻⁷). We also report compelling evidence for an interaction between the HLA-C and ERAP1 loci (combined P = 6.95 × 10⁻⁶). ERAP1 plays an important role in MHC class I peptide processing. ERAP1 variants only influenced psoriasis susceptibility in individuals carrying the HLA-C risk allele. Our findings implicate pathways that integrate epidermal barrier dysfunction with innate and adaptive immune dysregulation in psoriasis pathogenesis.

PMID:
20953190
PMCID:
PMC3749730
DOI:
10.1038/ng.694
[Indexed for MEDLINE]
Free PMC Article
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