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

Luykx, J.J.; Boks, M.P.M.; Terwindt, A.P.R.; Bakker, S.; Kahn, R.S.; Ophoff, R.A.

doi:10.1016/j.euroneuro.2010.02.008

« Previous Next »European Neuropsychopharmacology
Volume 20, Issue 6 , Pages 357-368, June 2010

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

J.J. Luykx
- Rudolf Magnus Institute of Neuroscience, Department of Psychiatry, University Medical Center Utrecht, B01.206, P.O. Box 85500, 3508 GA Utrecht, The Netherlands
- Corresponding author. Tel.: +31 88 7555555x3327; fax: +31 88 7555509.
M.P.M. Boks
- Rudolf Magnus Institute of Neuroscience, Department of Psychiatry, University Medical Center Utrecht, B01.206, P.O. Box 85500, 3508 GA Utrecht, The Netherlands
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
A.P.R. Terwindt
- Utrecht University/University Medical Center, Utrecht, The Netherlands
S. Bakker
- Rudolf Magnus Institute of Neuroscience, Department of Psychiatry, University Medical Center Utrecht, B01.206, P.O. Box 85500, 3508 GA Utrecht, The Netherlands
R.S. Kahn
- Rudolf Magnus Institute of Neuroscience, Department of Psychiatry, University Medical Center Utrecht, B01.206, P.O. Box 85500, 3508 GA Utrecht, The Netherlands
R.A. Ophoff
- Rudolf Magnus Institute of Neuroscience, Department of Psychiatry, University Medical Center Utrecht, B01.206, P.O. Box 85500, 3508 GA Utrecht, The Netherlands
- Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands
- Center for Neurobehavioral Genetics, University of California Los Angeles, Los Angeles, California, United States

Received 4 October 2009; received in revised form 17 January 2010; accepted 13 February 2010. published online 12 March 2010.

Abstract

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.

Keywords: GSK3β, Review, Gene, Genetics, Bipolar disorder