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; +59 more... 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 CA 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 EM Griffiths; Andre Reis; Juha Kere; Collaborative Association Study of Psoriasis (CASP); Genetic Analysis of Psoriasis Consortium; Psoriasis Association Genetics Extension; Wellcome Trust Case Control Consortium 2; Rajan P Nair; Andre Franke; Jonathan NWN Barker; Goncalo R Abecasis; James T Elder; Richard C Trembath; (2012) Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity. Nature genetics, 44 (12). pp. 1341-1348. ISSN 1061-4036 DOI: 10.1038/ng.2467
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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.
Item Type Article
Keywords caspase recruitment domain signaling protein, DNA directed DNA polymerase beta, immunoglobulin enhancer binding protein, methyl CpG binding protein 2, retinoic acid inducible protein I, STAT3 protein, transcription factor RUNX3, article, controlled study, Europe, gene identification, gene locus, genetic association, genetic susceptibility, genotype, host resistance, human, human cell, innate immunity, macrophage activation, major clinical study, priority journal, psoriasis, CARD Signaling Adaptor Proteins, Core Binding Factor Alpha 3 Subunit, DEAD-box RNA Helicases, European Continental Ancestry Group, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, GTPase-Activating Proteins, Guanylate Cyclase, Humans, Immunity, Innate, Membrane Proteins, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, Skin, STAT3 Transcription Factor, T-Lymphocytes, CARD Signaling Adaptor Proteins, genetics, immunology, Core Binding Factor Alpha 3 Subunit, genetics, immunology, DEAD-box RNA Helicases, genetics, immunology, European Continental Ancestry Group, genetics, GTPase-Activating Proteins, genetics, immunology, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Guanylate Cyclase, genetics, immunology, Humans, Immunity, Innate, genetics, Membrane Proteins, genetics, immunology, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, Psoriasis, genetics, immunology, STAT3 Transcription Factor, genetics, immunology, Skin, immunology, T-Lymphocytes, immunology
ISI 311713200013
Official URL http://www.scopus.com/inward/record.url?eid=2-s2.0...

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