Meta-analysis demonstrates lack of association of the GSK3B -50C/T polymorphism with risk of bipolar disorder.

Published data on the association between GSK3B -50C/T (rs334558) and bipolar disorder (BD) are inconclusive. We performed this meta-analysis to evaluate the relationship of this single-nucleotide polymorphism with the susceptibility, and with the age at onset of BD. A literature search was conducted though PubMed, EMBASE, Web of Science and China National Knowledge Infrastructure databases to identify relevant studies up to February 14, 2014. We identified a total of 6 publications including 1,251 cases and 1,804 controls to investigate the effect of GSK3B -50C/T on BD risk, and found no significant association in any genetic models (C vs. T: OR = 1.03, 95 % CI: 0.92-1.15; CC vs. TT+TC: OR = 1.04, 95 % CI: 0.84-1.28; TC+CC vs. TT: OR = 1.16, 95 % CI: 0.97-1.39; and CC vs. TC vs. TT: OR = 1.08, 95 % CI: 0.96-1.22). Subgroup analysis by ethnicity did not change the results. The association between GSK3B -50C/T and age at onset of BD was explored by 6 identified studies with a total of 659 BD type I patients. Similarly, we did not observe significant results in any genetic models (TC+CC vs. TT: SMD = 0.20, 95 % CI: -0.07 to 0.47; CC vs. TT+TC: SMD = 0.11, 95 % CI: -0.10 to 0.32; CC vs. TT: SMD = 0.32, 95 % CI: -0.13 to 0.77). The power analysis and tests for publication bias ensured the reliability of our results. In summary, this meta-analysis suggests that the functional polymorphism -50C/T within the GSK3B gene promoter is unlikely to relate with BD risk. However, more larger and well-designed studies are still needed to yield a conclusive result on the topic.