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

Genetic Analysis of Psoriasis Consortium & the Wellcome Trust Ca; Amy Strange; Francesca Capon; Chris CA Spencer; Jo Knight; Michael E Weale; Michael H Allen; Anne Barton; Gavin Band; Céline Bellenguez; +75 more... Judith GM Bergboer; Jenefer M Blackwell; Elvira Bramon; Suzannah J Bumpstead; Juan P Casas; Michael J Cork; Aiden Corvin; Panos Deloukas; Alexander Dilthey; Audrey Duncanson; Sarah Edkins; Xavier Estivill; Oliver Fitzgerald; Colin Freeman; Emiliano Giardina; Emma Gray; Angelika Hofer; Ulrike Hüffmeier; Sarah E Hunt; Alan D Irvine; Janusz Jankowski; Brian Kirby; Cordelia Langford; Jesús Lascorz; Joyce Leman; Stephen Leslie; Lotus Mallbris; Hugh S Markus; Christopher G Mathew; WH Irwin McLean; Ross McManus; Rotraut Mössner; Loukas Moutsianas; Asa T Naluai; Frank O Nestle; Giuseppe Novelli; Alexandros Onoufriadis; Colin NA Palmer; Carlo Perricone; Matti Pirinen; Robert Plomin; Simon C Potter; Ramon M Pujol; Anna Rautanen; Eva Riveira-Munoz; Anthony W Ryan; Wolfgang Salmhofer; Lena Samuelsson; Stephen J Sawcer; Joost Schalkwijk; Catherine H Smith; Mona Ståhle; Zhan Su; Rachid Tazi-Ahnini; Heiko Traupe; Ananth C Viswanathan; Richard B Warren; Wolfgang Weger; Katarina Wolk; Nicholas Wood; Jane Worthington; Helen S Young; Patrick LJM Zeeuwen; Adrian Hayday; A David Burden; Christopher EM Griffiths; Juha Kere; André Reis; Gilean McVean; David M Evans; Matthew A Brown; Jonathan N Barker; Leena Peltonen; Peter Donnelly; Richard C Trembath; (2010) A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1. Nature genetics, 42 (11). pp. 985-990. ISSN 1061-4036 DOI: 10.1038/ng.694

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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.

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
ISI	283540500016