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

Authors:
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 Cork, Xavier 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 Nair, Andre Franke, Jonathan N W N Barker, Goncalo R Abecasis, James T Elder, Richard C Trembath
Year of publication:
2012
Volume:
44
Issue:
12
Issn:
1061-4036
Journal title abbreviated:
NAT GENET
Journal title long:
Nature genetics
Impact factor:
31.616
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.