A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1 |
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| Authors: | Genetic Analysis of Psoriasis Consortium & the Wellcome Trust Case Control Consortium ,Strange Amy,Capon Francesca,Spencer Chris C A,Knight Jo,Weale Michael E,Allen Michael H,Barton Anne,Band Gavin,Bellenguez Céline,Bergboer Judith G M,Blackwell Jenefer M,Bramon Elvira,Bumpstead Suzannah J,Casas Juan P,Cork Michael J,Corvin Aiden,Deloukas Panos,Dilthey Alexander,Duncanson Audrey,Edkins Sarah,Estivill Xavier,Fitzgerald Oliver,Freeman Colin,Giardina Emiliano,Gray Emma,Hofer Angelika,Hüffmeier Ulrike,Hunt Sarah E,Irvine Alan D,Jankowski Janusz,Kirby Brian,Langford Cordelia,Lascorz Jesús |
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| Affiliation: | Wellcome Trust Centre for Human Genetics, Oxford, UK. |
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| 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?? and two loci with a combined P < 5 × 10??). We also report compelling evidence for an interaction between the HLA-C and ERAP1 loci (combined P = 6.95 × 10??). 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. |
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