Finally, although several previous studies reported associations of individual CpG methylation in the CLOCK, BMAL1, and PER2 genes with glucose-related traits, e.g., insulin resistance, obesity (Milagro et al., 2012), no study has systematically tested the joint effect of multiple CpGs in a candidate gene or the circadian pathway on glucose metabolism. Here, CLOCK is linked to obesity due to melanocortin 4 receptor deficiency.