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

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)-?B 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.

SUBMITTER: Tsoi LC 

PROVIDER: S-EPMC3510312 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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

Tsoi Lam C LC   Spain Sarah L SL   Knight Jo J   Ellinghaus Eva E   Stuart Philip E PE   Capon Francesca F   Ding Jun J   Li Yanming Y   Tejasvi Trilokraj T   Gudjonsson Johann E JE   Kang Hyun M HM   Allen Michael H MH   McManus Ross R   Novelli Giuseppe G   Samuelsson Lena L   Schalkwijk Joost J   Ståhle Mona M   Burden A David AD   Smith Catherine H CH   Cork Michael J MJ   Estivill Xavier X   Bowcock Anne M AM   Krueger Gerald G GG   Weger Wolfgang W   Worthington Jane J   Tazi-Ahnini Rachid R   Nestle Frank O FO   Hayday Adrian A   Hoffmann Per P   Winkelmann Juliane J   Wijmenga Cisca C   Langford Cordelia C   Edkins Sarah S   Andrews Robert R   Blackburn Hannah H   Strange Amy A   Band Gavin G   Pearson Richard D RD   Vukcevic Damjan D   Spencer Chris C A CC   Deloukas Panos P   Mrowietz Ulrich U   Schreiber Stefan S   Weidinger Stephan S   Koks Sulev S   Kingo Külli K   Esko Tonu T   Metspalu Andres A   Lim Henry W HW   Voorhees John J JJ   Weichenthal Michael M   Wichmann H Erich HE   Chandran Vinod V   Rosen Cheryl F CF   Rahman Proton P   Gladman Dafna D DD   Griffiths Christopher E M CE   Reis Andre A   Kere Juha J   Nair Rajan P RP   Franke Andre A   Barker Jonathan N W N JN   Abecasis Goncalo R GR   Elder James T JT   Trembath Richard C RC  

Nature genetics 20121111 12

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 w  ...[more]