These data characterizing the TCF21-AP-1 counter-regulatory pathway in CAD loci suggests that the epigenetic landscape in disease loci is more complex than previously thought and that part of the attributable risk for CAD-associated transcription factors such as TCF21 may be due in part to their functions in trans, mediated by epigenetic effects at other CAD loci across the genome. This evidence concerns the gene FOSB and coronary artery disorder.