期刊
JOURNAL OF PSYCHIATRY & NEUROSCIENCE
卷 43, 期 3, 页码 194-200出版社
CMA-CANADIAN MEDICAL ASSOC
DOI: 10.1503/jpn.170053
关键词
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资金
- Japan Agency for Medical Research and Development, AMED
- Research Group for Schizophrenia
- SENSHIN Medical Research Foundation
- [15K09809]
- [16K19768]
- Grants-in-Aid for Scientific Research [16H05375, 16K19768] Funding Source: KAKEN
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.
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