A large-scale screen for coding variants predisposing to psoriasis

Nat Genet. 2014 Jan;46(1):45-50. doi: 10.1038/ng.2827. Epub 2013 Nov 10.


To explore the contribution of functional coding variants to psoriasis, we analyzed nonsynonymous single-nucleotide variants (SNVs) across the genome by exome sequencing in 781 psoriasis cases and 676 controls and through follow-up validation in 1,326 candidate genes by targeted sequencing in 9,946 psoriasis cases and 9,906 controls from the Chinese population. We discovered two independent missense SNVs in IL23R and GJB2 of low frequency and five common missense SNVs in LCE3D, ERAP1, CARD14 and ZNF816A associated with psoriasis at genome-wide significance. Rare missense SNVs in FUT2 and TARBP1 were also observed with suggestive evidence of association. Single-variant and gene-based association analyses of nonsynonymous SNVs did not identify newly associated genes for psoriasis in the regions subjected to targeted resequencing. This suggests that coding variants in the 1,326 targeted genes contribute only a limited fraction of the overall genetic risk for psoriasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aminopeptidases / genetics
  • Asian Continental Ancestry Group / genetics
  • CARD Signaling Adaptor Proteins / genetics
  • Case-Control Studies
  • Connexin 26
  • Connexins / genetics
  • Female
  • Fucosyltransferases / genetics
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Guanylate Cyclase / genetics
  • Haplotypes
  • Humans
  • Male
  • Membrane Proteins / genetics
  • Minor Histocompatibility Antigens
  • Mutation, Missense
  • Nuclear Proteins / genetics
  • Polymorphism, Single Nucleotide*
  • Psoriasis / genetics*
  • RNA-Binding Proteins / genetics
  • Receptors, Interleukin / genetics
  • Young Adult


  • CARD Signaling Adaptor Proteins
  • Connexins
  • GJB2 protein, human
  • IL23R protein, human
  • Membrane Proteins
  • Minor Histocompatibility Antigens
  • Nuclear Proteins
  • RNA-Binding Proteins
  • Receptors, Interleukin
  • TARBP1 protein, human
  • Connexin 26
  • Fucosyltransferases
  • galactoside 2-alpha-L-fucosyltransferase
  • Aminopeptidases
  • ERAP1 protein, human
  • CARD14 protein, human
  • Guanylate Cyclase