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

Tsoi, Lam C. and Spain, Sarah L. and Knight, Jo and Ellinghaus, Eva and Stuart, Philip E. and Capon, Francesca and Ding, Jun and Li, Yanming and Tejasvi, Trilokraj and Gudjonsson, Johann E. and Kang, Hyun M. and Allen, Michael H. and McManus, Ross and Novelli, Giuseppe and Samuelsson, Lena and Schalkwijk, Joost and Ståhle, Mona and Burden, A. David and Smith, Catherine H. and Cork, Michael J. and Estivill, Xavier and Bowcock, Anne M. and Krueger, Gerald G. and Weger, Wolfgang and Worthington, Jane and Tazi-Ahnini, Rachid and Nestle, Frank O. and Hayday, Adrian and Hoffmann, Per and Winkelmann, Juliane and Wijmenga, Cisca and Langford, Cordelia and Edkins, Sarah and Andrews, Robert and Blackburn, Hannah and Strange, Amy and Band, Gavin and Pearson, Richard D. and Vukcevic, Damjan and Spencer, Chris C. A. and Deloukas, Panos and Mrowietz, Ulrich and Schreiber, Stefan and Weidinger, Stephan and Koks, Sulev and Kingo, Külli and Esko, Tonu and Metspalu, Andres and Lim, Henry W. and Voorhees, John J. and , Collaborative Association Study of Psoriasis (CASP) (2012) Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity. Nature Genetics, 44 (12). pp. 1341-1348. ISSN 1061-4036

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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.

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Journal Article
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Nature Genetics
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22 Jan 2016 13:46
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22 Nov 2022 02:50