The involvement of GSK3β in bipolar disorder: Integrating evidence from multiple types of genetic studies

We aimed to get a comprehensive insight into the genetic evidence supporting the role of GSK3β in bipolar disorder (BD). Using broad searches in NCBI's PubMed and the Genetic Association Database we looked for association, whole-genome linkage, genome-wide association, gene expression, pharmocogenomic, epigenetic, cytogenetic, and mouse model studies performed for BD until July 2009. Per gene, we rated the degree of converging evidence across these types of genetic studies. The genes most consistently associated with BD in the genetic studies we reviewed were GSK3β , GRK3, 5-HTTLPR, GRIN3, COMT, and GLUR3. GSK3β stood out as it was implicated in at least five types of genetic studies. Although our results are limited by design differences of included studies and possibly by publication bias, GSK3β is a plausible candidate gene for BD from a pharmacological and a genetic perspective. Future studies investigating the effects of GSK3β manipulation in BD seem warranted.