作者
Amy Strange,Francesca Capon,Chris C. A. Spencer,Jo Knight,Michael E. Weale,Michael Allen,Anne Barton,Gavin Band,Céline Bellenguez,Judith G.M. Bergboer,Jenefer M. Blackwell,Elvira Bramon,Suzannah 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 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,Åsa Torinsson Naluai,Frank O. Nestle,Giuseppe Novelli,Alexandros Onoufriadis,Colin N.A. Palmer,Carlo Perricone,Matti Pirinen,Robert Plomin,Simon Potter,Ramón M. Pujol,Anna Rautanen,Eva Riveira-Muñoz,Anthony W. Ryan,Wolfgang Salmhofer,Lena Samuelsson,Stephen Sawcer,Joost Schalkwijk,Catherine Smith,Mona Ståhle,Zhan Su,Rachid Tazi‐Ahnini,Heiko Traupe,Ananth C. Viswanathan,Debabrata Bandyopadhyay,Wolfgang Weger,Katarina Wolk,Nicholas W. Wood,Jane Worthington,Helen Young,Patrick L.J.M. Zeeuwen,Adrian Hayday,A. D. Burden,C.E.M. Griffiths,Juha Kere,André Reis,Gilean McVean,David M. Evans,Matthew A. Brown,Debabrata Bandyopadhyay,Leena Peltonen,Peter Donnelly,Richard C. Trembath
摘要
Richard Trembath, Peter Donnelly and colleagues report a genome-wide association study identifying six new psoriasis susceptibility loci. They also identify a statistical interaction between HLA-C and ERAP1 in psoriasis susceptibility. 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.