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

Author:

Hu Yiming1,Yu Miao12,Wang Yaqiang13,Wu Haotian12,Yang Xueqing1,Chen Xiangxin14,Wu Jing1

Affiliation:

1. National Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100050, China

2. School of Public Health, Inner Mongolia Medical University, Hohhot 010107, China

3. School of Public Health, China Medical University, Shenyang 110122, China

4. School of Public Health, Baotou Medical College, Baotou 014010, China

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.

Funder

National Center for Chronic and Noncommunicable Disease Control and Prevention

Publisher

MDPI AG

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