Large scale meta-analysis characterizes genetic architecture for common psoriasis associated variants

Nat Commun. 2017 May 24;8:15382. doi: 10.1038/ncomms15382.

Abstract

Psoriasis is a complex disease of skin with a prevalence of about 2%. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for psoriasis to date, including data from eight different Caucasian cohorts, with a combined effective sample size >39,000 individuals. We identified 16 additional psoriasis susceptibility loci achieving genome-wide significance, increasing the number of identified loci to 63 for European-origin individuals. Functional analysis highlighted the roles of interferon signalling and the NFκB cascade, and we showed that the psoriasis signals are enriched in regulatory elements from different T cells (CD8+ T-cells and CD4+ T-cells including TH0, TH1 and TH17). The identified loci explain ∼28% of the genetic heritability and generate a discriminatory genetic risk score (AUC=0.76 in our sample) that is significantly correlated with age at onset (p=2 × 10-89). This study provides a comprehensive layout for the genetic architecture of common variants for psoriasis.

Publication types

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

MeSH terms

  • Age of Onset
  • European Continental Ancestry Group / genetics*
  • Gene Regulatory Networks / genetics
  • Gene Regulatory Networks / immunology
  • Genetic Loci / genetics*
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study*
  • Humans
  • Interferons / immunology
  • Interferons / metabolism
  • NF-kappa B / immunology
  • NF-kappa B / metabolism
  • Polymorphism, Single Nucleotide
  • Protein Interaction Maps / genetics
  • Protein Interaction Maps / immunology
  • Psoriasis / genetics*
  • Psoriasis / immunology
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

  • NF-kappa B
  • Interferons