Risk variants for psoriasis vulgaris in a large case-control collection and association with clinical subphenotypes

Hum Mol Genet. 2012 Oct 15;21(20):4549-57. doi: 10.1093/hmg/dds295. Epub 2012 Jul 19.

Abstract

Recent genome-wide association studies (GWASs) have identified >20 new loci associated with the susceptibility to psoriasis vulgaris (PsV) risk. We investigated the association of PsV and its main clinical subphenotypes with 32 loci having previous genome-wide evidence of association with PsV (P < 5e-8) or strong GWAS evidence (P < 5e-5 in discovery and P < 0.05 in replication sample) in a large cohort of PsV patients (n = 2005) and controls (n = 1497). We provide the first independent replication for COG6 (P = 0.00079) and SERPINB8 (P = 0.048) loci with PsV. In those patients having developed psoriatic arthritis (n = 955), we found, for the first time, a strong association with IFIH1 (P = 0.013). Analyses of clinically relevant PsV subtypes yielded a significant association of severity of cutaneous disease with variation at LCE3D locus (P = 0.0005) in PsV and nail involvement with IL1RN in purely cutaneous psoriasis (PsC, P = 0.007). In an exploratory analysis of epistasis, we replicated the previously described HLA-C-ERAP1 interaction with PsC. Our findings show that common genetic variants associated with a complex phenotype like PsV influence different subphenotypes of high clinical relevance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Vesicular Transport / genetics
  • Adaptor Proteins, Vesicular Transport / metabolism
  • Alleles
  • Aminopeptidases / genetics
  • Aminopeptidases / metabolism
  • Case-Control Studies
  • Genetic Predisposition to Disease
  • Genetic Variation*
  • Genome-Wide Association Study
  • Genotype
  • HLA-C Antigens / genetics
  • HLA-C Antigens / immunology
  • Humans
  • Interleukin 1 Receptor Antagonist Protein / genetics
  • Male
  • Minor Histocompatibility Antigens
  • Phenotype*
  • Psoriasis / genetics*
  • Skin / immunology
  • Skin / metabolism

Substances

  • Adaptor Proteins, Vesicular Transport
  • COG6 protein, human
  • HLA-C Antigens
  • IL1RN protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Minor Histocompatibility Antigens
  • Aminopeptidases
  • ERAP1 protein, human