Remarkably, when tested in first-degree relatives (FDRs) of subjects with T1D who did not have diabetes or evidence of islet autoimmunity (autoantibody negative), both unmethylated and methylated CHTOP-817 and INS were also significantly increased compared to unrelated healthy control subjects (Fig. 5a–d), a result suggesting that underlying genetic risk may give rise to islet cell death. This evidence concerns the gene INS and type 1 diabetes mellitus.