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BMC Med Genet. 2015 Jul 26;16:54. doi: 10.1186/s12881-015-0197-7.

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

Author information

1
Department of Psychiatry, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto, Tokushima, 770-8503, Japan. shu-numata@umin.ac.jp.
2
Department of Psychiatry, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto, Tokushima, 770-8503, Japan. knst5511mkt@sunny.ocn.ne.jp.
3
Department of Bioinformatics and Genomics, Graduate School of Medical Sciences, Kanazawa University, 13-1, Takawamachi, Kanazawa, Ishikawa, 920-8640, Japan. atajima@med.kanazawa-u.ac.jp.
4
Department of Human Genetics, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto, Tokushima, 770-8503, Japan. atajima@med.kanazawa-u.ac.jp.
5
Department of Psychiatry, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto, Tokushima, 770-8503, Japan. aovestn@gmail.com.
6
Department of Human Genetics, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto, Tokushima, 770-8503, Japan. issehgen@tokushima-u.ac.jp.
7
Department of Psychiatry, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto, Tokushima, 770-8503, Japan. ohmori@tokushima-u.ac.jp.

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.

PMID:
26208850
PMCID:
PMC4557634
DOI:
10.1186/s12881-015-0197-7
[Indexed for MEDLINE]
Free PMC Article

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