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

Nat Genet. 2012 Dec;44(12):1341-8. doi: 10.1038/ng.2467. Epub 2012 Nov 11.

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.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • CARD Signaling Adaptor Proteins / genetics
  • CARD Signaling Adaptor Proteins / immunology
  • Core Binding Factor Alpha 3 Subunit / genetics
  • Core Binding Factor Alpha 3 Subunit / immunology
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / immunology
  • European Continental Ancestry Group / genetics
  • GTPase-Activating Proteins / genetics
  • GTPase-Activating Proteins / immunology
  • Genetic Loci*
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Guanylate Cyclase / genetics
  • Guanylate Cyclase / immunology
  • Humans
  • Immunity, Innate / genetics*
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology
  • Oligonucleotide Array Sequence Analysis
  • Polymorphism, Single Nucleotide
  • Psoriasis / genetics*
  • Psoriasis / immunology
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / immunology
  • Skin / immunology
  • T-Lymphocytes / immunology

Substances

  • CARD Signaling Adaptor Proteins
  • Core Binding Factor Alpha 3 Subunit
  • GTPase-Activating Proteins
  • Membrane Proteins
  • Runx3 protein, human
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • TAGAP protein, human
  • DDX58 protein, human
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases
  • CARD14 protein, human
  • CARD11 protein, human
  • Guanylate Cyclase