Association analysis of the glycogen synthase kinase-3beta gene in bipolar disorder

Glycogen synthase kinase-3beta (GSK3beta) is a target of lithium as well as sodium valproate, both of which are effective mood stabilizing prophylatics/treatments for bipolar disorder, a highly heritable psychiatric disorder. Though it is not clear whether the mood stabilizing effects of these drugs act directly through GSK3beta, it is a good candidate for mediating at least part of lithium's action, and is an aetiological candidate gene for the disease itself. Recently, a potential locus for bipolar disorder was reported on chromosome 3q, close to 3q13.37 where GSK3beta maps. We conducted an association study to test the hypothesis that polymorphism of GSK3beta is involved in susceptibility to bipolar disorder by examining association between GSK3beta-gene polymorphisms and bipolar disorder. Of the five polymorphisms we examined, three were very rare in the study population and were not examined further. Neither of the remaining two polymorphisms we examined showed association with bipolar disorder. Thus, it is unlikely that the GSK3beta-gene is a risk factor for bipolar disorder in our sample, but we cannot exclude the gene completely as other unknown polymorphisms in the gene may increase susceptibility.