By employing enhancer deletion in hESCs, we demonstrate that T2D-associated PSSE at the LAMA1 and CRB2 loci regulate LAMA1 and CRB2, respectively, and establish LAMA1 and CRB2 as the predominant target gene of their corresponding PSSE within TAD boundaries. Here, LAMA1 is linked to type 2 diabetes mellitus.