The HHEX and TCF7L2 gene variants contribute to T2DM by affecting insulin secretion (activating hepatocyte nuclear factor 1α) and action17–19, while MTNR1B impairs insulin secretion and glucose homeostasis, by downregulating adenylate or guanylate cyclase activity20. The gene discussed is TCF7L2; the disease is type 2 diabetes mellitus.