Decreased serum pyridoxal levels in schizophrenia: meta-analysis and Mendelian randomization analysis
Decreased serum pyridoxal levels in schizophrenia: meta-analysis and Mendelian randomization analysis
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DOI：
10.1503/jpn.170053
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发表时间：
2018-05-01
影响因子：
4.3
通讯作者：
Ohmori, Tetsuro
中科院分区：
文献类型：
--
作者：
Tomioka, Yukiko;Numata, Shusuke;Ohmori, Tetsuro
背景：一碳代谢的改变与精神分裂症有关，维生素B6是该途径的关键成分之一。方法：我们首先进行了一项病例对照研究血清吡哆醛水平和精神分裂症在一个大型的日本队列（n = 1276）。随后，我们对相关研究进行了荟萃分析（n = 2125）。其次，我们调查了rs 4654748，这是在全基因组关联研究中确定的维生素B6相关的单核苷酸多态性，是否在遗传上与精神分裂症患者在日本人口（n = 10 689）。最后，我们使用孟德尔随机化（MR）方法评估了血清吡哆醛水平对精神分裂症风险的影响。结果如下：精神分裂症患者的血清吡哆醛水平显著低于对照组，不仅在我们的队列中，而且在关联研究荟萃分析的汇总数据集中（标准化平均差异-0.48，95%置信区间[CI] -0.57至-0.39，p = 9.8 x 10（-24））。我们没有发现rs 4654748和精神分裂症之间的显著关联。此外，MR分析未能发现吡哆醛水平与精神分裂症风险之间的因果关系（比值比0.99，95%CI 0.65-1.51，p = 0.96）。局限性：在我们的横断面研究中，食物消耗和药物可能影响血清吡哆醛水平。精神分裂症患者的样本量、工具变量的数量和实质异质性是MR分析的局限性。结论：本观察性研究发现精神分裂症患者血清吡哆醛水平降低。然而，我们未能获得数据支持吡哆醛水平和精神分裂症风险之间的因果关系，使用MR方法。
Background: Alterations in one-carbon metabolism have been associated with schizophrenia, and vitamin B6 is one of the key components in this pathway. Methods: We first conducted a case-control study of serum pyridoxal levels and schizophrenia in a large Japanese cohort (n = 1276). Subsequently, we conducted a meta-analysis of association studies (n = 2125). Second, we investigated whether rs4654748, which was identified in a genome-wide association study as a vitamin B6-related single nucleotide polymorphism, was genetically implicated in patients with schizophrenia in the Japanese population (n = 10 689). Finally, we assessed the effect of serum pyridoxal levels on schizophrenia risk using a Mendelian randomization (MR) approach. Results: Serum pyridoxal levels were significantly lower in patients with schizophrenia than in controls, not only in our cohort, but also in the pooled data set of the meta-analysis of association studies (standardized mean difference -0.48, 95% confidence interval [CI] -0.57 to -0.39, p = 9.8 x 10(-24)). We failed to find a significant association between rs4654748 and schizophrenia. Furthermore, an MR analysis failed to find a causal relationship between pyridoxal levels and schizophrenia risk (odds ratio 0.99, 95% CI 0.65-1.51, p = 0.96). Limitations: Food consumption and medications may have affected serum pyridoxal levels in our cross-sectional study. Sample size, number of instrumental variables and substantial heterogeneity among patients with schizophrenia are limitations of an MR analysis. Conclusion: We found decreased serum pyridoxal levels in patients with schizophrenia in this observational study. However, we failed to obtain data supporting a causal relationship between pyridoxal levels and schizophrenia risk using the MR approach.