Genome-wide association study identifies three novel susceptibility loci for severe Acne vulgaris

Nat Commun. 2014 Jun 13;5:4020. doi: 10.1038/ncomms5020.

Abstract

Acne vulgaris (acne) is a common inflammatory disorder of the cutaneous pilo-sebaceous unit. Here we perform a genome-wide association analysis in the United Kingdom, comparing severe cases of acne (n=1,893) with controls (n=5,132). In a second stage, we genotype putative-associated loci in a further 2,063 acne cases and 1,970 controls. We identify three genome-wide significant associations: 11q13.1 (rs478304, Pcombined=3.23 × 10(-11), odds ratio (OR) = 1.20), 5q11.2 (rs38055, P(combined) = 4.58 × 10(-9), OR = 1.17) and 1q41 (rs1159268, P(combined) = 4.08 × 10(-8), OR = 1.17). All three loci contain genes linked to the TGFβ cell signalling pathway, namely OVOL1, FST and TGFB2. Transcripts of OVOL1 and TFGB2 have decreased expression in affected compared with normal skin. Collectively, these data support a key role for dysregulation of TGFβ-mediated signalling in susceptibility to acne.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acne Vulgaris / genetics*
  • Adult
  • Case-Control Studies
  • DNA-Binding Proteins / genetics
  • Female
  • Follistatin / genetics
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study*
  • Genotype
  • Humans
  • Male
  • Polymorphism, Single Nucleotide
  • Transcription Factors / genetics
  • Transforming Growth Factor beta2 / genetics
  • Young Adult

Substances

  • DNA-Binding Proteins
  • FST protein, human
  • Follistatin
  • OVOL1 protein, human
  • TGFB2 protein, human
  • Transcription Factors
  • Transforming Growth Factor beta2