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

Amy Strange, Francesca Capon, Chris C. A. Spencer, Jo Knight, Michael E. Weale, Michael H. Allen, Anne Barton, Gavin Band, Celine 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 EdkinsXavier Estivill, Oliver Fitzgerald, Colin Freeman, Emiliano Giardina, Emma Gray, Angelika Hofer, Ulrike Hueffmeier, Sarah E. Hunt, Alan D. Irvine, Janusz Jankowski, Brian Kirby, Cordelia Langford, Jesus Lascorz, Joyce Leman, Stephen Leslie, Lotus Mallbris, Hugh S. Markus, Christopher G. Mathew, W. H. Irwin McLean, Ross McManus, Rotraut Moessner, 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 Stahle, 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, Andre Reis, Gilean McVean, David M. Evans, Matthew A. Brown, Jonathan N. Barker, Leena Peltonen, Peter Donnelly, Richard C. Trembath

Research output: Contribution to journalArticlepeer-review

840 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)985 - 990
Number of pages6
JournalNature Genetics
Volume42
Issue number11
Early online date17 Oct 2010
DOIs
Publication statusPublished - Nov 2010

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