Figure 7. Fos/AP‐1 signaling activation was associated with clinical CAD/MI risk and heart failure.

A, Gene‐set based analysis of CAD/MI risk signaling in CARDIOGRAMPLUSC4D genome‐wide association meta‐analysis study (GWAS). Fos/AP‐1 target genes (222 genes), and Fos/AP‐1 target genes that were differentially expressed in patients with heart failure in RNA‐seq data set (56 genes/222 genes, GSE165303) were used as queried gene lists for magma analysis. B and C, Regional association plots showing CAD/MI risk‐loci. Fos/AP‐1 target genes, FAM177B (B) and BBOX1 (C) were identified as potential risk loci. Linkage disequilibrium (r ²) was calculated based on the combined 1000 genomes. D, Reanalyzing RNA‐seq data (GSE165303) of dilated cardiomyopathy (DCM) and control patients (CTL) to determine the dysregulated expression of Fos/AP‐1 signaling in heart failure. E through G, Using 222 Fos/AP‐1 target genes, the Fos/AP‐1 activity was determined in RNA‐seq data sets of control and DCM patients (E, GSE165303, n=51, 50 in CTL and DCM, respectively; Student's t tests), or control, DCM, and ischemic cardiomyopathy (ICM) patients (F, GSE116250, n=14, 37, 13, respectively; 1‐way ANOVA followed by Bonferroni test), or the normal, patients with ICM before and after left ventricular assist device (LVAD) treatment (G, GSE46224, n=8 for each group; 1‐way ANOVA followed by Bonferroni test). AP‐1 indicates activator protein 1; CAD, coronary atherosclerosis diseases; MI, myocardial infarction; SNP, single nucleotide polymorphism; and TF, transcriptional regulon.