These results support the critical role of KLF14 as a key age-, sex-, and obesity-specific transcriptional regulator affecting a large adipose-specific transregulatory network of metabolic traits and adiposity status, which provide further evidence for the differential genetic and epigenetic effects of KLF14 on the risk of cardiometabolic disorders. The gene discussed is KLF14; the disease is obesity due to melanocortin 4 receptor deficiency.