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. Nair, Andre Franke, Jonathan N W N Barker, Ggoncalo R. Abecasis, James T Eelder, Richard Ttrembath, Collaborative Association Study of Psoriasis (CASP), Genetic Analysis of Psoriasis Consortium (GAPC), Psoriasis Association Genetics Extension (PAGE), Wellcome Trust Case Control Consortium 2 (WTCCC2)

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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
Pages (from-to)1341-1348
Number of pages8
JournalNature Genetics
Issue number12
Publication statusPublished - 1 Dec 2012
Externally publishedYes

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