The mechanistic basis for the genetic association between FTO and obesity appears to be due to the disruption of AT-Rich Interaction Domain 5B repressor through the causal variants of FTO. The disruption results in loss of binding and activation of downstream targets Iroquois Homeobox 3 (IRX3) and IRX5 during early adipocyte differentiation [25]. Here, FTO is linked to obesity due to melanocortin 4 receptor deficiency.