OPRM1 and obesity due to melanocortin 4 receptor deficiency: Methylation of the combined five CpG sites analyzed in the promoter region of OPRM1 showed a significant increase in DNA methylation of humans with obesity for a long time (>5 years from onset) (CTRLs = 7.36 ± 0.51, obese = 11.51 ± 0.95; p < 0.001).