TF and obesity due to melanocortin 4 receptor deficiency: Another example of a long-range interaction of a causal variant is that of the previously mentioned rs1421085, which is associated with obesity risk and located in an intron of FTO. TFBS disruption analyses have shown that rs1421085 disrupts the ARID5B TF binding motif and affects the activity of an enhancer that regulates IRX3 and IRX5, genes located 1.2 Mb upstream, instead of the initially expected co-localized FTO gene itself [55,65].