Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity

Lam C. Tsoi, Sarah L. Spain, Jo Knight, Eva Ellinghaus, Philip E. Stuart, Francesca Capon, Jun Ding, Yanming Li, Trilokraj Tejasvi, Johann E. Gudjonsson, Hyun M. Kang, Michael H. Allen, Ross McManus, Giuseppe Novelli, Lena Samuelsson, Joost Schalkwijk, Mona Ståhle, A. David Burden, Catherine H. Smith, Michael J. CorkXavier Estivill, Anne M. Bowcock, Gerald G. Krueger, Wolfgang Weger, Jane Worthington, Rachid Tazi-Ahnini, Frank O. Nestle, Adrian Hayday, Per Hoffmann, Juliane Winkelmann, Cisca Wijmenga, Cordelia Langford, Sarah Edkins, Robert Andrews, Hannah Blackburn, Amy Strange, Gavin Band, Richard D. Pearson, Damjan Vukcevic, Chris C A Spencer, Panos Deloukas, Ulrich Mrowietz, Stefan Schreiber, Stephan Weidinger, Sulev Koks, Külli Kingo, Tonu Esko, Andres Metspalu, Henry W. Lim, John J. Voorhees, Michael Weichenthal, H. Erich Wichmann, Vinod Chandran, Cheryl F. Rosen, Proton Rahman, Dafna D. Gladman, Christopher E M Griffiths, Andre Reis, Juha Kere, Rajan P. Nnair, Andre Franke, Jonathan Nn Barker, Ggoncalo R. Abecasis, James Tt Eelder, Richard Ttrembath, Kristina Callis Duffin, Cindy Helms, David Goldgar, Yun Li, Justin Paschall, Mary J. Malloy, Clive R. Pullinger, John P. Kane, Jennifer Gardner, Amy Perlmutter, Andrew Miner, Bing Jian Feng, Ravi Hiremagalore, Robert W. Ike, Enno Christophers, Tilo Henseler, Andreas Ruether, Steven J. Schrodi, Sampath Prahalad, Stephen L. Guthery, Judith Fischer, Wilson Liao, Pui Kwok, Alan Menter, G. Mark Lathrop, C. Wise, Ann B. Begovich, Alexandros Onoufriadis, Michael E. Weale, Angelika Hofer, Wolfgang Salmhofer, Peter Wolf, Kati Kainu, Ulpu Saarialho-Kere, Sari Suomela, Petra Badorf, Ulrike Hüffmeier, Werner Kurrat, Wolfgang Küster, Jesús Lascorz, Rotraut Mössner, Funda Schürmeier-Horst, Markward Ständer, Heiko Traupe, Judith G M Bergboer, Martin Den Heijer, Peter C. Van De Kerkhof, Patrick L J M Zeeuwen, Louise Barnes, Linda E. Campbell, Caitriona Cusack, Ciara Coleman, Judith Conroy, Sean Ennis, Oliver Fitzgerald, Phil Gallagher, Alan D. Irvine, Brian Kirby, Trevor Markham, W. H Irwin McLean, Joe McPartlin, Sarah F. Rogers, Anthony W. Ryan, Agnieszka Zawirska, Emiliano Giardina, Tiziana Lepre, Carlo Perricone, Gemma Martín-Ezquerra, Ramon M. Pujol, Eva Riveira-Munoz, Annica Inerot, Åsa T. Naluai, Lotus Mallbris, Katarina Wolk, Joyce Leman, Anne Barton, Richard B. Warren, Helen S. Young, Isis Ricano-Ponce, Gosia Trynka, Fawnda J. Pellett, Andrew Henschel, Marin Aurand, Bruce Bebo, Christian Gieger, Thomas Illig, Susanne Moebus, Karl Heinz Jöckel, Raimund Erbel, Peter Donnelly, Leena Peltonen, Jenefer M. Blackwell, Elvira Bramon, Matthew A. Brown, Juan P. Casas, Aiden Corvin, Nicholas Craddock, Audrey Duncanson, Janusz Jankowski, Hugh S. Markus, Christopher G. Mathew, Mark I. McCarthy, Colin N A Palmer, Robert Plomin, Anna Rautanen, Stephen J. Sawcer, Nilesh Samani, Ananth C. Viswanathan, Nicholas W. Wood, Céline Bellenguez, Colin Freeman, Garrett Hellenthal, Eleni Giannoulatou, Matti Pirinen, Zhan Su, Sarah E. Hunt, Rhian Gwilliam, Suzannah J. Bumpstead, Serge Dronov, Matthew Gillman, Emma Gray, Naomi Hammond, Alagurevathi Jayakumar, Owen T. McCann, Jennifer Liddle, Marc L. Perez, Simon C. Potter, Radhi Ravindrarajah, Michelle Ricketts, Matthew Waller, Paul Weston, Sara Widaa, Pamela Whittaker, Rajan P. Neir, Jonathan N W N Barker, Goncalo R. Abecasis, James T. Elder, Richard C. Trembath

Research output: Contribution to journalArticle

557 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1341-1348
Number of pages8
JournalNature genetics
Volume44
Issue number12
DOIs
StatePublished - Dec 1 2012

ASJC Scopus subject areas

  • Genetics

Fingerprint Dive into the research topics of 'Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity'. Together they form a unique fingerprint.

Cite this