Genetic determinants of diabetes are similarly associated with other immune-mediated diseases

Purpose of review I discuss the increasing number of genes discovered to exert pleiotropic action on susceptibility to diabetes and simultaneously to other immune-mediated diseases. While a genetic correlation between type I diabetes and autoimmunity is not surprising, the mechanism of a relationship to other conditions such as atopy is less obvious. The recent wave of genome-wide association studies offers confirmation of previously recognized risk loci, but also novel loci that also are likely to act via multiple pathogenetic pathways. I will review this material more in a genetical than an immunological way. Recent findings Identification of IFIH1, an RNA helicase involved in the innate immune response to viral infection as a risk factor for type 1 diabetes and rheumatoid arthritis. Confirmation of the roles of CTLA4 and PTPN22 as general immune function modulators with a nonlinear dose-response effect on autoimmunity, and confirmation of the role of IL2RA, which may act via a regulatory T cell subset on immune disease risk. Expansion of the role of PPARG in immunity. Summary The wave of genome-wide association studies already experienced in the last 2 years has solidified what we thought we knew and added a list of genes in new pathways. The association of IFIH1 with type 1 diabetes may offer a real window into early events in the development of that disease.