Gene-wide association study between the methylenetetrahydrofolate reductase gene (MTHFR) and schizophrenia in the Japanese population, with an updated meta-analysis on currently available data

Methylenetetrahydrofolate reductase (MTHFR) is a critical molecule for single-carbon transfer reactions Recent evidence suggests that polymorphisms of MTHFR are related to neural tube deficits and the pathogenesis of schizophrenia While several studies have demonstrated associations between the gene encoding the MTHFR (MTHFR) polymorphisms and schizophrenia these studies lack consistency Therefore we conducted a gene wide association study (patients with schizophrenia = 696 control subjects = 747) and performed imputation analysis Additionally we performed meta-analysis on currently available data from 18 studies for two common functional polymorphisms (rs1801131 and rs1801133) There were no significant associations with schizophrenia in the single marker analysis for the seven tagging SNPs of MTHFR In the haplotypic analysis a nominally significant association was observed between the haplotypes which included four SNPs (rs1801133 rs17421511 rs17037396 and rs9651118) and the schizophrenic patients Additionally the imputation analysis demonstrated there were several associated markers on the MTHFR chromosomal region However confirmatory analyses of three tagging SNPs (rs1801133 rs17037396 and rs9651118) and the top SNP (rs17421511) for the imputation results (patients with schizophrenia = 797 control subjects = 1025) failed to replicate the haplotypic analysis and the imputation results These findings suggest that MTHFR polymorphisms are unlikely to be related to the development of schizophrenia in the Japanese population However since our meta-analysis results demonstrated strong support for association of rs1801133 with schizophrenia further replication studies based on a gene-wide approach need to be considered (C) 2010 Elsevier B V All rights reserved