A functional framework for interpretation of genetic associations in T1D

► Genetic susceptibility to T1D is a composite of risk factors contributed by the major histocompatibility complex with a large number of additional genetic modifiers. ► The functional properties of each of these susceptibility genes vary owing to subtle genetic variation that occurs normally in the population. ► Identification of functional pathways impacted by specific GWAS 'hits' link disease progression to distinct steps in immune activation, expansion, and regulation. ► Stratification of risk based on genetic variation provides a classification scheme that implicates distinct functional pathways as therapeutic targets.