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

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Abstract

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.

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Authors and Affiliations

  1. Department of Radiation Oncology, The Second Affiliated Hospital, and Cancer Institute, Zhejiang University School of Medicine, Jiefang Road 88, Hangzhou, 310009, People’s Republic of China

    Guodi Chen, Guangwei Yu & Liancong Wang

  2. Wuhan Mental Health Center, Tongji Medical College, Huazhong University of Science and Technology, Youyi Road 70, Wuhan, 430022, People’s Republic of China

    Jun Tang & Yao Zhang

  3. Department of Psychiatry, The Second Affiliated Hospital, Zhejiang University School of Medicine, Jiefang Road 88, Hangzhou, 310009, People’s Republic of China

    Yiping Chen

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  1. Guodi Chen
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  2. Jun Tang
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  3. Guangwei Yu
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Correspondence to Yao Zhang.

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Guodi Chen and Jun Tang contributed equally to this study.

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Supplementary material 1 (DOC 47 kb)

11033_2014_3441_MOESM2_ESM.tif

Supplementary Fig. S1 Forest plots and Begg’s funnel plots for the overall association between GSK3B −50C/T and bipolar disorder risk in other genetic models. a–b Forest plot (a) and Begg’s funnel plot (b) in the CC versus TT+TC model (the recessive model). c–d Forest plot (c) and Begg’s funnel plot (d) in the TC+CC versus TT model (the dominant model). e–f Forest plot (e) and Begg’s funnel plot (f) in the CC versus TC versus TT model (the log-additive model). (TIFF 801 kb)

11033_2014_3441_MOESM3_ESM.tif

Supplementary Fig. S2 Forest plots and Begg’s funnel plots for the overall association between GSK3B −50C/T and the age at onset of disorder risk in other genetic models. a–b Forest plot (a) and Begg’s funnel plot (b) in the CC versus TT+TC model (the recessive model). c–d Forest plot (c) and Begg’s funnel plot (d) in the CC versus TT model. (TIFF 537 kb)

11033_2014_3441_MOESM4_ESM.tif

Supplementary Fig. S3 Statistical power analysis. It presents the study power for detecting a significant association between GSK3B −50C/T and bipolar disorder risk based on the allelic data in this meta-analysis (α = 0.05, controls/cases ratio = 1.44, and C allele frequency in controls = 0.441). The power in our study is 45, 76 and 94 % when OR is 1.10, 1.15 and 1.20, respectively. (TIFF 607 kb)

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Chen, G., Tang, J., Yu, G. et al. Meta-analysis demonstrates lack of association of the GSK3B −50C/T polymorphism with risk of bipolar disorder. Mol Biol Rep 41, 5711–5718 (2014). https://doi.org/10.1007/s11033-014-3441-x

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