Abstract
Objective
Although previous epidemiological studies have demonstrated that serum uric acid (SUA) is associated with major depressive disorder (MDD), these analyses are prone to biases. Here, we applied the Mendelian Randomization approach to determine whether SUA is causally associated with MDD.
Methods
We conducted a meta-analysis to evaluate the relationship between SUA and MDD, then applied summary data from the Global Urate Genetics Consortium and the Psychiatric Genomics Consortium to estimate their causal effect using a two-sample bidirectional Mendelian Randomization (MR) analysis. Thereafter, the causal effect was further researched using genetic risk scores (GRS) as instrumental variables (IVs).
Results
Results of a meta-analysis of articles comprising 6975 and 13,589 MDD patients and controls, respectively, revealed that SUA was associated with MDD (SMD = −0.690, 95% CI: −0.930 to −0.440, I2 = 97.4%, P < 0.001). In addition, the five MR methods revealed no causal relationship existed between SUA and MDD, which corroborated the results obtained via the GRS approach.
Conclusion
This paper found little evidence that this association between SUA and MDD is casual. Genetically, there was no significant causal association between SUA and MDD.
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Data availability
All datasets used in this study are publicly available, included in the main manuscript or its supplementary information files.
Code availability
The codes used for all analyses are available on request.
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Acknowledgements
We would like to acknowledge the Global Urate Genetics Consortium (GUGC) and the Psychiatric Genomics Consortium (PGC) for supplying the summary data. This study was funded by the Major Project of Guangxi Innovation Driven (AA18118016), National Key Research and Development Program of China (2017YFC0908000), Scientific Research and Technology Development Program of Guangxi (15277004).
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ZC and SL designed research; YB and JL conducted research; JL and ZM analyzed data, and ML, SX and SSH wrote the paper. ZC had primary responsibility for the final content. All authors read and approved the final manuscript.
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Chen, Z., Liang, S., Bai, Y. et al. Serum uric acid is not associated with major depressive disorder in European and South American populations: a meta-analysis and two-sample bidirectional Mendelian Randomization study. Eur J Clin Nutr 76, 1665–1674 (2022). https://doi.org/10.1038/s41430-022-01165-8
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DOI: https://doi.org/10.1038/s41430-022-01165-8