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