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


Strange, A; Capon, F; Spencer, CCA; Knight, J; Weale, ME; Allen, MH; Barton, A; Band, G; Bellenguez, C; Bergboer, JGM; 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; Huffmeier, U; Hunt, SE; Irvine, AD; Jankowski, J; Kirby, B; Langford, C; Lascorz, J; Leman, J; Leslie, S; Mallbris, L; Markus, HS; Mathew, CG; McLean, WHI; McManus, R; Mossner, R; Moutsianas, L; Naluai, AT; Nestle, FO; Novelli, G; Onoufriadis, A; Palmer, CNA; Perricone, C; Pirinen, M; Plomin, R; Potter, SC; Pujol, RM; Rautanen, A; Riveira-Munoz, E; Ryan, AW; Salmhofer, W; Samuelsson, L; Sawcer, SJ; Schalkwijk, J; Smith, CH; Stahle, M; Su, Z; Tazi-Ahnini, R; Traupe, H; Viswanathan, AC; Warren, RB; Weger, W; Wolk, K; Wood, N; Worthington, J; Young, HS; Zeeuwen, P; Hayday, A; Burden, AD; Griffiths, CEM; Kere, J; Reis, A; McVean, G; Evans, DM; Brown, MA; Barker, JN; Peltonen, L; Donnelly, P; Trembath, RC; (2010) A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1. Nature genetics, 42 (11). 985-U106. ISSN 1061-4036 DOI: https://doi.org/10.1038/ng.694

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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 x 10(-8) and two loci with a combined P < 5 x 10(-7)). We also report compelling evidence for an interaction between the HLA-C and ERAP1 loci (combined P = 6.95 x 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.

Item Type: Article
Keywords: STATISTICAL-METHOD, DISEASES, GENE, VARIANTS, AUTOIMMUNITY, RESPONSES, PATHWAYS, COMPLEX, FAMILY, SCAN, Aminopeptidases, genetics, Chromosome Mapping, Chromosomes, Human, genetics, Chromosomes, Human, X, genetics, Europe, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, HLA-C Antigens, genetics, Humans, Major Histocompatibility Complex, genetics, Polymorphism, Single Nucleotide, Psoriasis, genetics, Reference Values, Risk Assessment
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Non-Communicable Disease Epidemiology
Research Centre: Centre for Global Non-Communicable Diseases (NCDs)
PubMed ID: 20953190
Web of Science ID: 283540500016
URI: http://researchonline.lshtm.ac.uk/id/eprint/2143

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