IRX5 and obesity due to melanocortin 4 receptor deficiency: To identify the target genes under the genetic control of the rs1421085 CRM, we examined gene expression levels of five candidate target genes contained within the TAD, namely, Rpgrip1l, Fto, Irx3, Irx5, and Irx6. Obesogenic WAT expansion is mainly regulated by hypothalamic signals in the brain and WAT-intrinsic mechanisms (20), and both tissues have been previously implicated in the FTO obesity risk locus (2, 4, 6, 7).