• ADAR1 RNA editing is a critical regulatory mechanism of innate immune activation through preventing endogenous double-strand RNA sensing

• Human genetics implicates dsRNA sensing and the inadequate ADAR1 RNA editing as a causal mechanism of coronary artery disease

• Through comprehensive studies utilizing human genetics, primary in vitro culture, mouse models of disease, and single-cell RNA sequencing, we have defined the mechanism by which ADAR1 RNA editing and dsRNA sensing by MDA5 mediates atherosclerotic disease risk