RGD Reference Report - Homocysteine, methylenetetrahydrofolate reductase and risk of schizophrenia: a meta-analysis. - Rat Genome Database

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Homocysteine, methylenetetrahydrofolate reductase and risk of schizophrenia: a meta-analysis.

Authors: Muntjewerff, JW  Kahn, RS  Blom, HJ  Den Heijer, M 
Citation: Muntjewerff JW, etal., Mol Psychiatry. 2006 Feb;11(2):143-9.
RGD ID: 6893466
Pubmed: PMID:16172608   (View Abstract at PubMed)
DOI: DOI:10.1038/sj.mp.4001746   (Journal Full-text)

Elevated plasma homocysteine concentration has been suggested as a risk factor for schizophrenia, but the results of epidemiological studies have been inconsistent. The most extensively studied genetic variant in the homocysteine metabolism is the 677C>T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene, resulting in reduced enzyme activity and, subsequently, in elevated homocysteine. A meta-analysis of eight retrospective studies (812 cases and 2113 control subjects) was carried out to examine the association between homocysteine and schizophrenia. In addition, a meta-analysis of 10 studies (2265 cases and 2721 control subjects) on the homozygous (TT) genotype of the MTHFR 677C>T polymorphism was carried out to assess if this association is causal. A 5 micromol/l higher homocysteine level was associated with a 70% (95% confidence interval, CI: 27-129) higher risk of schizophrenia. The TT genotype was associated with a 36% (95% CI: 7-72) higher risk of schizophrenia compared to the CC genotype. The performed meta-analyses showed no evidence of publication bias or excessive influence attributable to any given study. In conclusion, our study provides evidence for an association of homocysteine with schizophrenia. The elevated risk of schizophrenia associated with the homozygous genotype of the MTHFR 677C>T polymorphism provides support for causality between a disturbed homocysteine metabolism and risk of schizophrenia.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
schizophrenia susceptibilityIAGP 6893466DNA:transition:cds:g.677C>T (human)RGD 
schizophrenia susceptibilityISOMTHFR (Homo sapiens)6893466; 6893466DNA:transition:cds:g.677C>T (human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Atypical behavior susceptibilityIAGP 6893466DNA:transition:cds:g.677C>TRGD 
Objects Annotated

Genes (Rattus norvegicus)
Mthfr  (methylenetetrahydrofolate reductase)

Genes (Mus musculus)
Mthfr  (methylenetetrahydrofolate reductase)

Genes (Homo sapiens)
MTHFR  (methylenetetrahydrofolate reductase)


Additional Information