Journal
SCIENCE
Volume 343, Issue 6175, Pages 1118-+Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1246949
Keywords
-
Categories
Funding
- Wellcome Trust [074318, 088891, 090532/Z/09/Z]
- European Research Council (ERC) under the European Union [281824]
- Medical Research Council [98082]
- National Institute for Health and Research Oxford Biomedical Research Centre
- Medical Research Council [G1001708] Funding Source: researchfish
- National Institute for Health Research [ACF-2008-13-017, CL-2012-13-004] Funding Source: researchfish
- MRC [G1001708] Funding Source: UKRI
Ask authors/readers for more resources
To systematically investigate the impact of immune stimulation upon regulatory variant activity, we exposed primary monocytes from 432 healthy Europeans to interferon-gamma (IFN-gamma) or differing durations of lipopolysaccharide and mapped expression quantitative trait loci (eQTLs). More than half of cis-eQTLs identified, involving hundreds of genes and associated pathways, are detected specifically in stimulated monocytes. Induced innate immune activity reveals multiple master regulatory trans-eQTLs including the major histocompatibility complex (MHC), coding variants altering enzyme and receptor function, an IFN-beta cytokine network showing temporal specificity, and an interferon regulatory factor 2 (IRF2) transcription factor-modulated network. Induced eQTL are significantly enriched for genome-wide association study loci, identifying context-specific associations to putative causal genes including CARD9, ATM, and IRF8. Thus, applying pathophysiologically relevant immune stimuli assists resolution of functional genetic variants.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available