Rethinking the genetic basis for comorbidity of schizophrenia and type 2 diabetes

Abstract

The co-occurrence of schizophrenia (SCZ) and type 2 diabetes mellitus (T2D) has been well documented. This review article focuses on the hypothesis that the co-occurrence of SCZ and T2D may be, at least in part, driven by shared genetic factors. Previous genetic studies of T2D and SCZ evidence have disclosed a number of overlapped risk loci. However, the putative common genetic factors for SCZ and T2D remain inconclusive due to inconsistent findings. A systemic review of methods of identifying genetic loci contributing to the comorbidity link between SCZ and T2D is hence needed. In the current review article, we have discussed several different approaches to localizing the shared susceptibility genes for these two diseases. To begin with, one could start with probing the gene involved in both glucose and dopamine metabolisms. Additionally, hypothesis-free genome-wide association studies (GWAS) may provide more clues to the common genetic basis for these two diseases. Genetic similarities inferred from GWAS may shed some light on the genetic mechanism underlying the comorbidity link between SCZ and T2D. Meanwhile, endophenotypes (e.g., adiponectin level in T2D and working memory in SCZ) may serve as alternative phenotypes that are more directly influenced by genes than target diseases. Hence, endophenotypes of these diseases may be more tractable to identification. To summarize, novel approaches are needed to dissect the complex genetic basis of the comorbidity of SCZ and T2D.