In this study, we identified 12 shared genes (EPHA3, RASIP1, PENK, LRRC17, CEBPB, EFEMP2, UBAP1, PPP1R15A, SPEN, MAFF, GADD45B and KLF4) and investigated the underlying comorbidity mechanism between T2DM and OA. Here, PENK is linked to type 2 diabetes mellitus.