We have previously implicated the noncoding variant rs1421085 as a causal variant at the FTO obesity risk locus linking rs1421085 to specific effector genes (IRX3 and IRX5) and their cellular functions (mitochondrial energy expenditure following β-adrenergic receptor activation) in human subcutaneous adipocyte progenitors (4). Here, IRX5 is linked to obesity due to melanocortin 4 receptor deficiency.