For the downregulated and hypermethylated genes, the most significant results comprised the MAPK signaling pathway, vascular smooth muscle contraction, focal adhesion, calcium signaling pathway, cGMP-PKG signaling pathway, axon guidance, cell adhesion molecules, dilated cardiomyopathy, hypertrophic cardiomyopathy, morphine addiction and renin secretion (Figure S1h). Here, REN is linked to hypertrophic cardiomyopathy.