Purpose of review
The genetic basis of type 1 diabetes (T1D) is being characterized through DNA sequence variation and cell type specificity. This review discusses the current understanding of the genes and variants implicated in risk of T1D and how genetic information can be used in prediction, intervention and components of clinical care.
Fine mapping and functional studies has provided resolution of the heritable basis of T1D risk, incorporating novel insights on the dominant role of human leukocyte antigen (HLA) genes as well as the lesser impact of non-HLA genes. Evaluation of T1D-associated single nucleotide polymorphisms (SNPs), there is enrichment of genetic effects restricted to specific immune cell types (CD4+ and CD8+ T cells, CD19+ B cells and CD34+ stem cells), suggesting pathways to improved prediction. In addition, T1D-associated SNPs have been used to generate genetic risk scores (GRS) as a tool to distinguish T1D from type 2 diabetes (T2D) and to provide prediagnostic data to target those for autoimmunity screening (e.g. islet autoantibodies) as a prelude for continuous monitoring and entry into intervention trials.
Genetic susceptibility accounts for nearly one-half of the risk for T1D. Although the T1D-associated SNPs in white populations account for nearly 90% of the genetic risk, with high sensitivity and specificity, the low prevalence of T1D makes the T1D GRS of limited utility. However, identifying those with highest genetic risk may permit early and targeted immune monitoring to diagnose T1D months prior to clinical onset.