Scientific Publications

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

Publication TypeJournal Article
AuthorsLee, MN, Ye C., Villani AC, Raj T., Li W., Eisenhaure TM, Imboywa SH, Chipendo PI, Ran FA, Slowikowski K., Ward LD, Raddassi K., McCabe C., Lee MH, Frohlich IY, Hafler DA, Kellis M., Raychaudhuri S., Zhang F., Stranger BE, Benoist CO, De Jager PL, Regev A., and Hacohen N.
AbstractLittle 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.
Year of Publication2014
JournalScience (New York, N.Y.)
Volume343
Issue6175
Pages1246980
Date Published (YYYY/MM/DD)2014/03/07
ISSN Number0036-8075
DOI10.1126/science.1246980
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/24604203?dopt=Abstract