Evidence for epistatic interactions in humans include a study by Winkler et al. that genotyped 12 non-HLA susceptibility genes (ERBB3, PTPN2, IFIH1, PTPN22, CLEC16A, CD25, CTLA4, SH2B3, IL2, IL18RAP, IL10, and COBL) in high-risk HLA positive children of parents with T1D that were prospectively followed from birth to the development of autoantibodies and disease (19). This evidence concerns the gene IL18RAP and type 1 diabetes mellitus.