INS and type 2 diabetes mellitus: Interestingly, some of these SNPs showed a strong enrichment in the T2D genes or novel candidate genes, e. g. ADCY5, ANK1, PPARG, TCF7L2, THADA, WFS1, and ZMIZ1. We identified 18 super enhancer SNPs enriched in T2D-associated gene ADCY5, this gene encodes a member of the membrane-bound adenylyl cyclase enzymes which are expressed in heart, brain, and pancreatic β cells, etc. Adenylyl cyclases mediate G-protein coupled receptor signaling through the synthesis of the second messenger cAMP, which can modulate glucose-stimulated insulin secretion by several possible mechanisms [52].