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.
journal_name
Nat Genetjournal_title
Nature geneticsauthors
Genetic Analysis of Psoriasis Consortium & the Wellcome Trust Case Control Consortium 2.,Strange A,Capon F,Spencer CC,Knight J,Weale ME,Allen MH,Barton A,Band G,Bellenguez C,Bergboer JG,Blackwell JM,Bramon E,Bumpstead SJ,Casadoi
10.1038/ng.694subject
Has Abstractpub_date
2010-11-01 00:00:00pages
985-90issue
11eissn
1061-4036issn
1546-1718pii
ng.694journal_volume
42pub_type
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