| Literature DB >> 20953190 |
Amy Strange, Francesca Capon, Chris C A Spencer, Jo Knight, Michael E Weale, Michael H Allen, Anne Barton, Gavin Band, Céline Bellenguez, Judith G M 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, W H Irwin McLean, Ross McManus, Rotraut Mössner, Loukas Moutsianas, Asa T Naluai, Frank O Nestle, Giuseppe Novelli, Alexandros Onoufriadis, Colin N A 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 L J M Zeeuwen, Adrian Hayday, A David Burden, Christopher E M Griffiths, Juha Kere, André Reis, Gilean McVean, David M Evans, Matthew A Brown, Jonathan N Barker, Leena Peltonen, Peter Donnelly, Richard C Trembath.
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.Entities:
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Year: 2010 PMID： 20953190 PMCID： PMC3749730 DOI： 10.1038/ng.694
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330