ABSTRACT
AIMS: To conduct a systematic review in order to comprehensively synthesize the findings from a diverse range of genetically informative studies on comorbid depression and type 2 diabetes. METHODS: Database searches (1 January 2008 to 1 June 2020) in PubMed and EMBASE were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Eligible reports employed any type of genetically informed design, including twin modelling, Mendelian randomization, genome-wide association studies, polygenetic risk scores, or linkage disequilibrium score regression. Searches generated 451 unique citations, and 16 manuscripts met the inclusion criteria. RESULTS: The included studies addressed three aetiological models of the depression-diabetes relationship: uni- or bi-directional phenotypic causation; shared genetic liability; or gene-environment interaction. From these studies, there is modest evidence that type 2 diabetes is causally related to risk of developing depression, but much more limited evidence that depression is causally related to risk of diabetes. There is little evidence of shared genetic liability between depression and diabetes or of gene-environment interaction. CONCLUSIONS: Findings from genetically informed studies are mixed but provide some support for the uni- or bi-directional phenotypic model of depression and type 2 diabetes. Future studies should also explore the hypothesis that this relationship may be influenced by shared environmental risk factors. Findings can inform multifaceted approaches to diabetes prevention and care that reflect how psychosocial factors contribute to type 2 diabetes risk and outcomes.
