Common genetic variants modulate pathogen-sensing responses in human dendritic cells

Science. 2014 Mar 7;343(6175):1246980. doi: 10.1126/science.1246980.


Little is known about how human genetic variation affects the responses to environmental stimuli in the context of complex diseases. Experimental and computational approaches were applied to determine the effects of genetic variation on the induction of pathogen-responsive genes in human dendritic cells. We identified 121 common genetic variants associated in cis with variation in expression responses to Escherichia coli lipopolysaccharide, influenza, or interferon-β (IFN-β). We localized and validated causal variants to binding sites of pathogen-activated STAT (signal transducer and activator of transcription) and IRF (IFN-regulatory factor) transcription factors. We also identified a common variant in IRF7 that is associated in trans with type I IFN induction in response to influenza infection. Our results reveal common alleles that explain interindividual variation in pathogen sensing and provide functional annotation for genetic variants that alter susceptibility to inflammatory diseases.

Publication types

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

MeSH terms

  • Adult
  • Autoimmune Diseases / genetics
  • Communicable Diseases / genetics
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Escherichia coli
  • Female
  • Gene-Environment Interaction*
  • Genetic Loci
  • Genome-Wide Association Study
  • HEK293 Cells
  • Host-Pathogen Interactions / genetics*
  • Humans
  • Influenza A virus
  • Interferon Regulatory Factor-7 / genetics*
  • Interferon-beta / pharmacology
  • Lipopolysaccharides / immunology
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci
  • STAT Transcription Factors / genetics*
  • Transcriptome
  • Young Adult


  • IRF7 protein, human
  • Interferon Regulatory Factor-7
  • Lipopolysaccharides
  • STAT Transcription Factors
  • Interferon-beta

Associated data

  • GEO/GSE53166