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

Journal article published in 2010 by Genetic_Analysis_of_Psoriasis_Consortium_&_the_Wellcome_Trust_Case_Control_Consortium_2, Pl J. M. Zeeuwen, Hs S. Young, Me E. Weale, McLean Wh, Ac C. Viswanathan, Rb B. Warren, Mona Ståhle, Rc C. Trembath, Anne Barton ORCID, Amy Strange, Gavin Band, Capon F Spencer CC Knight J Weale ME Allen MH Barton A Band G Bellenguez C Bergboer JG Blackwell JM Bramon E Bumpstead SJ Casas JP Cork MJ Corvin A Deloukas P Dilthey A Duncanson A Edkins S Estivill X Fitzgerald O Freeman C Giardina E Gray E Hofer A Hüffme Strange A., Céline Bellenguez, Allen Mh and other authors.
This paper is available in a repository.
This paper is available in a repository.

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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 × 10⁻⁸ 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.