National Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100050, China.
School of Public Health, Inner Mongolia Medical University, Hohhot 010107, China.
Nutrients. 2024 Jun 21;16(13):1986. doi: 10.3390/nu16131986.
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, = 0.046) and bipolar affective disorders (OR: 1.85, 95% CI: 1.16-2.96, = 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.
先前的研究表明，B 族维生素和同型半胱氨酸（Hcy）可能与精神障碍有关，但准确的因果关系仍不清楚。本研究旨在通过两样本 Mendelian 随机化（MR）研究阐明血清 B 族维生素和 Hcy 水平与五种常见精神障碍之间的潜在因果关系。在这项 MR 分析中，从一个大型全基因组关联研究（GWAS）数据库中获得了 50 个与叶酸相关的单核苷酸多态性（SNP）-13 个与维生素 B6 相关，8 个与维生素 B12 相关，12 个与 Hcy 相关的 SNP，并将其用作工具变量（IV）。使用逆方差加权（IVW）、加权中位数（WM）、MR-Egger 方法进行 MR 分析，并进一步进行敏感性分析以测试稳健性。这项 MR 研究发现，血清维生素 B12 水平与焦虑障碍（比值比（OR）：1.34，95%置信区间（CI）：1.01-1.78， = 0.046）和双相情感障碍（OR：1.85，95% CI：1.16-2.96， = 0.010）的风险之间存在暗示性因果关系。然而，叶酸、维生素 B6 和 Hcy 水平可能与精神障碍的风险没有因果关系。总之，这项研究表明，血清维生素 B12 水平升高可能暗示性地增加焦虑和双相情感障碍的风险，尽管不能完全消除水平遗传异质性。我们研究结果的潜在意义需要在基于不同人群的更大规模 GWAS 中进行验证。
