Our model suggests that IRF1 mediates the effect of the IL27 SNP on expression levels of STAT1. Moreover, our functional studies with the mutated form of IL-27 confirmed its decreased capacity to activate the STAT1 pathway, and we showed that a potential causal variant (the missense variant rs181206) for T1D susceptibility and changes in IRF1 and STAT1 expression is shared. Here, IL27 is linked to type 1 diabetes mellitus.