With regards to MetS, MC4R is the largest known single risk factor for combined obesity and T2DM manifestation, as replicated by several GWAS studies (Chambers et al., 2008; Loos et al., 2008; Thorleifsson et al., 2009; Willer et al., 2009). Here, MC4R is linked to obesity due to melanocortin 4 receptor deficiency.