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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.

Original publication

DOI

10.1038/ng.694

Type

Journal article

Journal

Nature genetics

Publication Date

11/2010

Volume

42

Pages

985 - 990

Addresses

Wellcome Trust Centre for Human Genetics, Oxford, UK.

Keywords

Genetic Analysis of Psoriasis Consortium & the Wellcome Trust Case Control Consortium 2, Chromosomes, Human, Chromosomes, Human, X, Humans, Psoriasis, Genetic Predisposition to Disease, Aminopeptidases, HLA-C Antigens, Minor Histocompatibility Antigens, Risk Assessment, Chromosome Mapping, Major Histocompatibility Complex, Polymorphism, Single Nucleotide, Reference Values, Europe, Genetic Variation, Genome-Wide Association Study