Examples of genome-wide significant age-associated sites include CpG loci located in the promoter region of the obesity gene LEP [53], the childhood obesity gene OLFM4 [53], the T2D gene IRS2 [54], and the newly identified MetS gene TFAP2B [55] (Figure 3A–D). Here, IRS2 is linked to obesity due to melanocortin 4 receptor deficiency.