The involvement of GSK3beta 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 GSK3beta 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 GSK3beta , GRK3, 5-HTTLPR, GRIN3, COMT, and GLUR3. GSK3beta 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, GSK3beta is a plausible candidate gene for BD from a pharmacological and a genetic perspective. Future studies investigating the effects of GSK3beta manipulation in BD seem warranted.
Rudolf Magnus Institute of Neuroscience, Department of Psychiatry, University Medical Center Utrecht, B01.206, P.O. Box 85500, 3508 GA Utrecht, The Netherlands. j.luykx@umcutrecht.nl
J J
JJ
Luykx
M P M
MP
Boks
A P R
AP
Terwindt
S
S
Bakker
R S
RS
Kahn
R A
RA
Ophoff
D000818:Animals; D001714:Bipolar Disorder / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics*; D003625:Data Collection; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D008040:Genetic Linkage / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D055106:Genome-Wide Association Study; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D051379:Mice; D010597:Pharmacogenetics
D038362:Glycogen Synthase Kinase 3