Polymorphisms in the INS gene predicted development of T1D.63 Although the effect of each individual gene is small, the combination of family history of T1D, the HLA-DR3/4-DQB1*0302 genotype, and the susceptibility variants of PTPN22, UBASH2, and INS increased the risk of islet autoimmunity 16-fold and that of T1D 40-fold.63 Here, PTPN22 is linked to type 1 diabetes mellitus.