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

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, Mössner, Rotraut, 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 and Trembath, Richard C. (2010) A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1. Nature Genetics, 42 11: 985-990. doi:10.1038/ng.694


Author 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
Mössner, Rotraut
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.
Title A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1
Journal name Nature Genetics   Check publisher's open access policy
ISSN 1061-4036
1546-1718
Publication date 2010-11-01
Year available 2010
Sub-type Article (original research)
DOI 10.1038/ng.694
Open Access Status Not yet assessed
Volume 42
Issue 11
Start page 985
End page 990
Total pages 6
Place of publication New York, NY, United States
Publisher Nature Publishing Group
Language eng
Subject 1311 Genetics
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.
Formatted abstract
To identify new susceptibility loci for psoriasis, we undertOk a genome-wide asociation study of 594,224 SNPs in 2,622 individuals with psoriasis and 5,667 controls. We identified asociations at eight previously unreported genomic loci. Seven loci harbored genes with recognized iMune functions (IL28RA, REL, IFIH1, ERAP1, TRAF3IP2, NFKBIA and TYK2). These asociations 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 compeLing evidence for an interaction betwEn the HLA-C and ERAP1 loci (combined P = 6.95-10-6). ERAP1 plays an important role in MHC claS I peptide proceSing. ERAP1 variants only influenced psoriasis susceptibility in individuals carrying the HLA-C risk aLele. Our findings implicate pathways that integrate epidermal barrier dysfunction with iNate and adaptive iMune dysregulation in psoriasis pathogenesis. © 2010 Nature America, Inc. All rights reserved.
Keyword Statistical-method
Disease
Gene interaction
ERAP1 protein
HLA C antigen
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 083948/Z/07/Z
Tr 228/5-4
IZKF B32/A8
SAF 2008-00357
078173/Z/05/Z
17552
G0601387
G0000934
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
UQ Diamantina Institute Publications
 
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Created: Sun, 21 Nov 2010, 10:01:29 EST