Genome-wide association studies (GWAS) have provided a wealth of information on potential disease-associated genes in the human population. In particular, several loci have been associated with type 2 diabetes (T2D). However, due to the complexity of the disease, it has been a challenge to unravel the exact effects of specific loci on T2D pathogenesis. In this issue of the JCI, Keller and colleagues developed a systems genetic approach to identify insulin secretion–associated genes in nondiabetic mice followed by tissue-level and functional phenotyping. Several of the loci identified were syntenic with human T2D-related loci, indicating that this approach may be feasible for discerning genetic variation in nondiabetic individuals that may lead to the development of T2D.
Mark A. Herman, Jonathan E. Campbell, David A. D’Alessio