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BMC Medical Genetics
Published in: BMC Medical Genetics 1/2015

Open Access 01-12-2015 | Research article

Evaluation of an association between plasma total homocysteine and schizophrenia by a Mendelian randomization analysis

Authors: Shusuke Numata, Makoto Kinoshita, Atsushi Tajima, Akira Nishi, Issei Imoto, Tetsuro Ohmori

Published in: BMC Medical Genetics | Issue 1/2015

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Abstract

Background

The results of meta-analyses conducted by previous association studies between total homocysteine and schizophrenia suggest that an elevated total homocysteine level is a risk factor for schizophrenia. However, observational studies have potential limitations, such as confounding and reverse causation. In the present study, we evaluated a causal relationship between plasma total homocysteine and schizophrenia by conducting a Mendelian randomization analysis.

Methods

We used the MTHFR C677T polymorphism as an instrumental variable, which affects the plasma total homocysteine levels. To calculate the risk estimate for the association of this single nucleotide polymorphism (SNP) with schizophrenia, we conducted a meta-analysis of case–control studies that comprise a total of 11,042 patients with schizophrenia and 14,557 control subjects. We obtained an estimate for the association of this SNP with the plasma total homocysteine levels from a meta-analysis of genome-wide association studies comprising 44,147 individuals.

Results

By combining these two estimates, we demonstrated a significant effect of the plasma total homocysteine on schizophrenia risk, representing an OR of 2.15 (95 % CI = 1.39–3.32; p = 5.3 x 10−4) for schizophrenia per 1-SD increase in the natural log-transformed plasma total homocysteine levels.

Conclusions

We provided evidence of a causal relationship between the plasma total homocysteine and schizophrenia, and this result will add insight into the pathology and treatment of schizophrenia.
Appendix
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Metadata
Title
Evaluation of an association between plasma total homocysteine and schizophrenia by a Mendelian randomization analysis
Authors
Shusuke Numata
Makoto Kinoshita
Atsushi Tajima
Akira Nishi
Issei Imoto
Tetsuro Ohmori
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2015
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/s12881-015-0197-7

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