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. 2024 Jun 21;16(13):1986.
doi: 10.3390/nu16131986.

Exploring the Association between Serum B Vitamins, Homocysteine and Mental Disorders: Insights from Mendelian Randomization

Yiming Hu  1 , Miao Yu  1   2 , Yaqiang Wang  1   3 , Haotian Wu  1   2 , Xueqing Yang  1 , Xiangxin Chen  1   4 , Jing Wu  1
Affiliations

Exploring the Association between Serum B Vitamins, Homocysteine and Mental Disorders: Insights from Mendelian Randomization

Yiming Hu et al. Nutrients. .

Abstract

Previous studies show that B vitamins and homocysteine (Hcy) may be associated with mental disorders, but the accurate causal relationship remains unclear. This study aimed to elucidate the potential causal relationship of serum B vitamins and Hcy levels with five common mental disorders through a two-sample Mendelian randomization (MR) study. In this MR analysis, 50 single-nucleotide polymorphisms (SNPs)-13 related to folate, 17 to vitamin B6, 8 to vitamin B12 and 12 to Hcy-were obtained from a large-scale Genome-Wide Association Studies (GWAS) database and employed as instrumental variables (IVs). The MR analyses were conducted using the inverse variance weighted (IVW), weighted median (WM), MR-Egger methods and sensitivity analyses were further performed to test the robustness. This MR study found a suggestive causal relationships between serum vitamin B12 levels and the risk of anxiety disorders (odds ratio (OR): 1.34, 95% confidence interval (CI): 1.01-1.78, p = 0.046) and bipolar affective disorders (OR: 1.85, 95% CI: 1.16-2.96, p = 0.010). However, folate, vitamin B6 and Hcy levels may not be causally associated with the risk of mental disorders. In conclusion, this study reveals that elevated serum vitamin B12 levels might suggestively increase the risk of anxiety and bipolar affective disorders, even though horizontal pleiotropy cannot be completely eliminated. The potential implications of our results warrant validation in larger GWAS based on diverse populations.

Keywords: B vitamins; homocysteine; mendelian randomization; mental disorders.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
An overview of the study design.
Figure 2
Figure 2
Causal effect of folate on mental disorders in MR analyses. SNP: single nucleotide polymorphisms; OR: odds ratio; CI: confidence interval; p value: p value of the causal estimate.
Figure 3
Figure 3
Causal effect of vitamin B6 on mental disorders in MR analyses. SNP: single nucleotide polymorphisms; OR: odds ratio; CI: confidence interval; p value: p value of the causal estimate.
Figure 4
Figure 4
Causal effect of vitamin B12 on mental disorders in MR analyses. SNP: single nucleotide polymorphisms; OR: odds ratio; CI: confidence interval; p value: p value of the causal estimate.
Figure 5
Figure 5
Causal effect of homocysteine on mental disorders in MR analyses. SNP: single nucleotide polymorphisms; OR: odds ratio; CI: confidence interval; p value: p value of the causal estimate.
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Grants and funding

This work was supported by the project of National Center for Chronic and Noncommunicable Disease Control and Prevention “Long-term health effects of early-life interventions in family cohorts” (Project No: 202327).
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