The present two stage case-control study, using Exome Sequencing and follow-up MassARRAY genotyping of selected genes reported association of polymorphism in PPARG, HNF4A, GLIS3, MTNR1B, IRS-2, and NOTCH2 with T2DM in Pashtun ethnic population for the first time. The gene discussed is IRS2; the disease is type 2 diabetes mellitus.