The data examines reconfiguration of the 3D genome due to nucleotide differences associated with T1D. Chromatin organization at T cell identity genes is identical between diabetes-susceptible and diabetes-resistant mouse strains despite thousands of sequence polymorphisms, suggesting that these loci are epigenetically resilient to genetic variation. However, molecular and optical mapping of genome folding demonstrate that diabetes risk-conferring loci coalesce into close spatial proximity in T cells of diabetes-susceptible mice, forming regulatory cliques, and resulting in aberrant gene expression. Our data uncover 3D chromatin architecture asa new dimension in understanding complex diseases.