Abstract
To gain further insight into the genetic architecture of psoriasis, we conducted a meta-analysis of 3 genome-wide association studies (GWAS) and 2 independent data sets genotyped on the Immunochip, including 10,588 cases and 22,806 controls. We identified 15 new susceptibility loci, increasing to 36 the number associated with psoriasis in European individuals. We also identified, using conditional analyses, five independent signals within previously known loci. The newly identified loci shared with other autoimmune diseases include candidate genes with roles in regulating T-cell function (such as RUNX3, TAGAP and STAT3). Notably, they included candidate genes whose products are involved in innate host defense, including interferon-mediated antiviral responses (DDX58), macrophage activation (ZC3H12C) and nuclear factor (NF)-κB signaling (CARD14 and CARM1). These results portend a better understanding of shared and distinctive genetic determinants of immune-mediated inflammatory disorders and emphasize the importance of the skin in innate and acquired host defense.
| Originalsprache | Englisch |
|---|---|
| Seiten (von - bis) | 1341-1348 |
| Seitenumfang | 8 |
| Fachzeitschrift | Nature Genetics |
| Jahrgang | 44 |
| Ausgabenummer | 12 |
| DOIs | |
| Publikationsstatus | Veröffentlicht - 1 Dez. 2012 |
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in: Nature Genetics, Jahrgang 44, Nr. 12, 01.12.2012, S. 1341-1348.
Publikation: Beitrag in Fachzeitschrift › Artikel › Begutachtung
TY - JOUR
T1 - Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity
AU - Tsoi, Lam C.
AU - Spain, Sarah L.
AU - Knight, Jo
AU - Ellinghaus, Eva
AU - Stuart, Philip E.
AU - Capon, Francesca
AU - Ding, Jun
AU - Li, Yanming
AU - Tejasvi, Trilokraj
AU - Gudjonsson, Johann E.
AU - Kang, Hyun M.
AU - Allen, Michael H.
AU - McManus, Ross
AU - Novelli, Giuseppe
AU - Samuelsson, Lena
AU - Schalkwijk, Joost
AU - Ståhle, Mona
AU - Burden, A. David
AU - Smith, Catherine H.
AU - Cork, Michael J.
AU - Estivill, Xavier
AU - Bowcock, Anne M.
AU - Krueger, Gerald G.
AU - Weger, Wolfgang
AU - Worthington, Jane
AU - Tazi-Ahnini, Rachid
AU - Nestle, Frank O.
AU - Hayday, Adrian
AU - Hoffmann, Per
AU - Winkelmann, Juliane
AU - Wijmenga, Cisca
AU - Langford, Cordelia
AU - Edkins, Sarah
AU - Andrews, Robert
AU - Blackburn, Hannah
AU - Strange, Amy
AU - Band, Gavin
AU - Pearson, Richard D.
AU - Vukcevic, Damjan
AU - Spencer, Chris C.A.
AU - Deloukas, Panos
AU - Mrowietz, Ulrich
AU - Schreiber, Stefan
AU - Weidinger, Stephan
AU - Koks, Sulev
AU - Kingo, Külli
AU - Esko, Tonu
AU - Metspalu, Andres
AU - Lim, Henry W.
AU - Voorhees, John J.
AU - Weichenthal, Michael
AU - Wichmann, H. Erich
AU - Chandran, Vinod
AU - Rosen, Cheryl F.
AU - Rahman, Proton
AU - Gladman, Dafna D.
AU - Griffiths, Christopher E.M.
AU - Reis, Andre
AU - Kere, Juha
AU - Nnair, Rajan P.
AU - Franke, Andre
AU - Barker, Jonathan Nn
AU - Abecasis, Ggoncalo R.
AU - Eelder, James Tt
AU - Ttrembath, Richard
AU - Duffin, Kristina Callis
AU - Helms, Cindy
AU - Goldgar, David
AU - Paschall, Justin
AU - Malloy, Mary J.
AU - Pullinger, Clive R.
AU - Kane, John P.
AU - Gardner, Jennifer
AU - Perlmutter, Amy
AU - Miner, Andrew
AU - Feng, Bing Jian
AU - Hiremagalore, Ravi
AU - Ike, Robert W.
AU - Christophers, Enno
AU - Henseler, Tilo
AU - Ruether, Andreas
AU - Schrodi, Steven J.
AU - Prahalad, Sampath
AU - Guthery, Stephen L.
AU - Fischer, Judith
AU - Liao, Wilson
AU - Kwok, Pui
AU - Menter, Alan
AU - Lathrop, G. Mark
AU - Wise, C.
AU - Begovich, Ann B.
AU - Onoufriadis, Alexandros
AU - Weale, Michael E.
AU - Hofer, Angelika
AU - Salmhofer, Wolfgang
AU - Wolf, Peter
AU - Kainu, Kati
AU - Saarialho-Kere, Ulpu
AU - Suomela, Sari
AU - Badorf, Petra
AU - Hüffmeier, Ulrike
AU - Kurrat, Werner
AU - Küster, Wolfgang
AU - Lascorz, Jesús
AU - Mössner, Rotraut
AU - Schürmeier-Horst, Funda
AU - Ständer, Markward
AU - Traupe, Heiko
AU - Bergboer, Judith G.M.
AU - Heijer, Martin Den
AU - Van De Kerkhof, Peter C.
AU - Zeeuwen, Patrick L.J.M.
AU - Barnes, Louise
AU - Campbell, Linda E.
AU - Cusack, Caitriona
AU - Coleman, Ciara
AU - Conroy, Judith
AU - Ennis, Sean
AU - Fitzgerald, Oliver
AU - Gallagher, Phil
AU - Irvine, Alan D.
AU - Kirby, Brian
AU - Markham, Trevor
AU - McLean, W. H.Irwin
AU - McPartlin, Joe
AU - Rogers, Sarah F.
AU - Ryan, Anthony W.
AU - Zawirska, Agnieszka
AU - Giardina, Emiliano
AU - Lepre, Tiziana
AU - Perricone, Carlo
AU - Martín-Ezquerra, Gemma
AU - Pujol, Ramon M.
AU - Riveira-Munoz, Eva
AU - Inerot, Annica
AU - Naluai, Åsa T.
AU - Mallbris, Lotus
AU - Wolk, Katarina
AU - Leman, Joyce
AU - Barton, Anne
AU - Warren, Richard B.
AU - Young, Helen S.
AU - Ricano-Ponce, Isis
AU - Trynka, Gosia
AU - Pellett, Fawnda J.
AU - Henschel, Andrew
AU - Aurand, Marin
AU - Bebo, Bruce
AU - Gieger, Christian
AU - Illig, Thomas
AU - Moebus, Susanne
AU - Jöckel, Karl Heinz
AU - Erbel, Raimund
AU - Donnelly, Peter
AU - Peltonen, Leena
AU - Blackwell, Jenefer M.
AU - Bramon, Elvira
AU - Brown, Matthew A.
AU - Casas, Juan P.
AU - Corvin, Aiden
AU - Craddock, Nicholas
AU - Duncanson, Audrey
AU - Jankowski, Janusz
AU - Markus, Hugh S.
AU - Mathew, Christopher G.
AU - McCarthy, Mark I.
AU - Palmer, Colin N.A.
AU - Plomin, Robert
AU - Rautanen, Anna
AU - Sawcer, Stephen J.
AU - Samani, Nilesh
AU - Viswanathan, Ananth C.
AU - Wood, Nicholas W.
AU - Bellenguez, Céline
AU - Freeman, Colin
AU - Hellenthal, Garrett
AU - Giannoulatou, Eleni
AU - Pirinen, Matti
AU - Su, Zhan
AU - Hunt, Sarah E.
AU - Gwilliam, Rhian
AU - Bumpstead, Suzannah J.
AU - Dronov, Serge
AU - Gillman, Matthew
AU - Gray, Emma
AU - Hammond, Naomi
AU - Jayakumar, Alagurevathi
AU - McCann, Owen T.
AU - Liddle, Jennifer
AU - Perez, Marc L.
AU - Potter, Simon C.
AU - Ravindrarajah, Radhi
AU - Ricketts, Michelle
AU - Waller, Matthew
AU - Weston, Paul
AU - Widaa, Sara
AU - Whittaker, Pamela
AU - Neir, Rajan P.
AU - Elder, James T.
AU - Trembath, Richard C.
N1 - Funding Information: Major support for this study was provided by the US National Institutes of Health, the Wellcome Trust and the German Research Foundation. We thank J.C. Barrett for contribution to the design of the Immunochip and helpful analytical discussion, as well as E. Gray, S. Bumpstead, D. Simpkin and the staff of the Wellcome Trust Sanger Institute Sample Management and Genotyping teams for their genotyping and analytical contributions. We acknowledge use of the British 1958 Birth Cohort DNA collection, funded by the UK Medical Research Council (G0000934) and the Funding Information: Wellcome Trust (068545/Z/02), and the UK National Blood Service controls, funded by the Wellcome Trust. We acknowledge CASP for the contribution of GWAS data, as well as the provision of control DNA samples by the Cooperative Research in the Region of Augsburg (KORA) and Heinz-Nixdorf Recall (Risk Factors, Evaluation of Coronary Calcification and Lifestyle) study (HNR) and genotyping data generated by the Dietary, Lifestyle and Genetic determinants of Obesity and Metabolic syndrome (DILGOM) Consortium. We thank the Barbara and Neal Henschel Charitable Foundation for their support of the National Psoriasis Victor Henschel BioBank. We acknowledge the Genetic repository in Ireland for Psoriasis and Psoriatic Arthritis (GRIPPsA), the Irish blood transfusion service/Trinity College Dublin Biobank and the Dublin Centre for Clinical Research (funded by the Health Research Board and the Wellcome Trust). A detailed list of contributing consortia and relevant funding support is provided in the Supplementary Note.
PY - 2012/12/1
Y1 - 2012/12/1
N2 - To gain further insight into the genetic architecture of psoriasis, we conducted a meta-analysis of 3 genome-wide association studies (GWAS) and 2 independent data sets genotyped on the Immunochip, including 10,588 cases and 22,806 controls. We identified 15 new susceptibility loci, increasing to 36 the number associated with psoriasis in European individuals. We also identified, using conditional analyses, five independent signals within previously known loci. The newly identified loci shared with other autoimmune diseases include candidate genes with roles in regulating T-cell function (such as RUNX3, TAGAP and STAT3). Notably, they included candidate genes whose products are involved in innate host defense, including interferon-mediated antiviral responses (DDX58), macrophage activation (ZC3H12C) and nuclear factor (NF)-κB signaling (CARD14 and CARM1). These results portend a better understanding of shared and distinctive genetic determinants of immune-mediated inflammatory disorders and emphasize the importance of the skin in innate and acquired host defense.
AB - To gain further insight into the genetic architecture of psoriasis, we conducted a meta-analysis of 3 genome-wide association studies (GWAS) and 2 independent data sets genotyped on the Immunochip, including 10,588 cases and 22,806 controls. We identified 15 new susceptibility loci, increasing to 36 the number associated with psoriasis in European individuals. We also identified, using conditional analyses, five independent signals within previously known loci. The newly identified loci shared with other autoimmune diseases include candidate genes with roles in regulating T-cell function (such as RUNX3, TAGAP and STAT3). Notably, they included candidate genes whose products are involved in innate host defense, including interferon-mediated antiviral responses (DDX58), macrophage activation (ZC3H12C) and nuclear factor (NF)-κB signaling (CARD14 and CARM1). These results portend a better understanding of shared and distinctive genetic determinants of immune-mediated inflammatory disorders and emphasize the importance of the skin in innate and acquired host defense.
UR - http://www.scopus.com/inward/record.url?scp=84870512735&partnerID=8YFLogxK
U2 - 10.1038/ng.2467
DO - 10.1038/ng.2467
M3 - Article
C2 - 23143594
AN - SCOPUS:84870512735
SN - 1061-4036
VL - 44
SP - 1341
EP - 1348
JO - Nature Genetics
JF - Nature Genetics
IS - 12
ER -