Meta-analysis Report

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Basic Info

Reference	Hu C.Y., 2014 PMID: 24938371
Citation	Hu, C. Y., et al. (2014). "Methylenetetrahydrofolate reductase (MTHFR) polymorphism susceptibility to schizophrenia and bipolar disorder: an updated meta-analysis." J Neural Transm.
Disease Type	Bipolar Disorder & Schizophrenia
Study Type	Candidate-gene association study

Detail Info

Samples	A total of 38 articles were identified through a search of electronic databases. 27,060 subjects(11,646 patients and 15,414 controls) with genotyping of MTHFR C677T, and 14,811 subjects (6,265 patients and 8,546 controls) with genotyping of MTHFR A1298C.
Statistic Method	Pooled ORs and 95% confidence intervals (CIs) were calculated using four genetic models, and the recessive model (TT vs. CT+CC/CC vs. AC+AA). The distribution of the genotypes in the control groups were examined for Hardyâ€“Weinberg equilibrium (HWE) using the Chi-square test. Possible heterogeneity between-study was investigated using Q test and I² statistic. The random effect model was used to calculate ORs with their 95%CIs in this meta-analysis. Sensitivity analyses were performed by removing studies not in HWE from the meta-analysis. Besides, subgroup analyses were conducted by ethnicity. Finally, funnel plots, Begg's and Egger's test were used to assess possible publication bias. All analyses were performed using Stata 9.0 (StataCrop, College station, Tex). All the P values were two sided, and P value<0.05 was considered statistically significant.
Basic Result	Meta-analysis showed that MTHFR C677T was significantly associated with SZ, the highest OR was found for the recessive model (for TT vs. CT+CC: OR=1.34, 95%CI: 1.18â€“1.53); a marginal association of MTHFR C677T with increased risk of BPD has also been found for the recessive model (OR=1.26, 95%CI: 1.00-1.59). Subgroup analysis by ethnicity indicated that the significant association with SZ and BPD existed among Asian and African populations, but not for the white. MTHFR A1298C was significant associated with SZ, the highest OR for the dominant model (OR=1.13, 95%CI: 1.03-1.24). Subgroup analysis indicated a significant association with SZ existed in Asian populations, not among the white populations and no significant association was detected between the MTHFR A1298C and BPD in all groups.

Genetic factors reported by this study for BD

Other variants reported by this study for BD (count: 2)

Variant Name	Related Gene	Type	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
MTHFR exon 7 A1298C	MTHFR	SNP	A/C		White: C vs. A: OR=1.32, 95%CI=1.05-1.66, P-value=0.017; CC + AC vs. AA: OR=1.33, 95%CI=1.08-1.64, P-value=0.008; CC vs. AC + AA: OR=1.85, 95%CI=1.02-3.34, P-value=0.042; CC vs. AA: OR=2.03, 95%CI=1.07-2.86, P-value=0.031	Significant association was found between the MTHFR A1298C p...... Significant association was found between the MTHFR A1298C polymorphism and BPD in all genetic models. More...	Positive
MTHFR exon 4 C677T	MTHFR	SNP	C/T		All studies: T vs. C: OR=1.03, 95%CI=0.86-1.23, P-value=0.765; TT + CT vs. CC: OR=1.17, 95%CI=0.94-1.46, P-value=0.152; TT vs. CT + CC: OR=1.26, 95%CI=1.00-1.59, P-value=0.048; TT vs. CC: OR=1.30, 95%CI=0.96-1.76, P-value=0.092. white: T vs. C: OR=1.02, 95%CI=0.67-1.57, P-value=0.919; TT + CT vs. CC: OR=1.01, 95%CI=0.61-1,65, P-value=0.981; TT vs. CT + CC: OR=1.07, 95%CI=0.57-1.98, P-value=0.84; TT vs. CC: OR=1.05, 95%CI=0.49-2.24, P-value=0.909. Asian: T vs. C: OR=1.07, 95%CI=0.94-1.21, P-value=0.311; TT + CT vs. CC: OR=1.07, 95%CI=0.89-1.29, P-value=0.456; TT vs. CT + CC: OR=1.32, 95%CI=1.03-1.69, P-value=0.031; TT vs. CC: OR=1.28, 95%CI=0.97-1.69, P-value=0.081. African: T vs. C: OR=0.88, 95%CI=0.34-2.30, P-value=0.793; TT + CT vs. CC: OR=1.83, 95%CI=1.25-2.69, P-value=0.002; TT vs. CT + CC: OR=1.56, 95%CI=0.81-3.04, P-value=0.186; TT vs. CC: OR=1.97, 95%CI=0.99-3.92, P-value=0.054.	Subgroup analysis by ethnicity indicated that the significan...... Subgroup analysis by ethnicity indicated that the significant association with BPD existed among Asian and African populations, but not for the white. More...	Positive

Genes reported by this study for BD (count: 1)

Gene	Statistical Values/Author Comments	Result Category
MTHFR	We conclude that MTHFR polymorphism is associated with BPD among Asian, African populations, but not...... We conclude that MTHFR polymorphism is associated with BPD among Asian, African populations, but not the white. More...	Positive

Genetic factors reported by this study for SZ and/or MDD

Other variants reported by this study for SZ/MDD

Disease	Variant Name	Related Gene	Type	Statistical Values	Description	Result Category
SZ	MTHFR exon 4 C677T	MTHFR	SNP	All studies: T vs. C: OR=1.15, 95%CI=1.07-1.23, P-value=<0.001; TT + CT vs. CC: OR=1.14, 95%CI=1.05-1.24, P-value=0.001; TT vs. CT + CC: OR=1.34, 95%CI=1.18-1.53, P-value=<0.001; TT vs. CC: OR=1.33, 95%CI=1.15-1.54, P-value=<0.001. white: T vs. C: OR=1.07, 95%CI=0.98-1.16, P-value=0.141; TT + CT vs. CC: OR=1.07, 95%CI=0.96-1.18, P-value=0.217; TT vs. CT + CC: OR=1.13, 95%CI=0.95-1.36, P-value=0.17; TT vs. CC: OR=1.15, 95%CI=0.94-1.40, P-value=0.173. Asian: T vs. C: OR=1.21, 95%CI=1.08-1.34, P-value=0.001; TT + CT vs. CC: OR=1.22, 95%CI=1.07-1.38, P-value=0.003; TT vs. CT + CC: OR=1.50, 95%CI=1.26-1.78, P-value=<0.001; TT vs. CC: OR=1.46, 95%CI=1.19-1.78, P-value=<0.001. African: T vs. C: OR=2.14, 95%CI=1.42-3.23, P-value=<0.001; TT + CT vs. CC: OR=1.85, 95%CI=1.10-3.09, P-value=0.02; TT vs. CT + CC: OR=4.28, 95%CI=1.76-10.29, P-value=0.001; TT vs. CC: OR=4.67, 95%CI=1.89-11.57, P-value=0.001	Meta-analysis showed that MTHFR C677T was significantly associated with SZ.	Positive
SZ	MTHFR exon 7 A1298C	MTHFR	SNP	All studies: C vs. A: OR=1.08, 95%CI=0.99-1.18, P-value=0.081; CC + AC vs. AA: OR=1.10, 95%CI=1.00-1.22, P-value=0.049; CC vs. AC + AA: OR=1.13, 95%CI=0.95-1.35, P-value=0.166; CC vs. AA: OR=1.18, 95%CI=0.97-1.44, P-value=0.104. white: C vs. A: OR=1.07, 95%CI=0.96-1.19, P-value=0.218; CC + AC vs. AA: OR=1.08, 95%CI=0.95-1.23, P-value=0.217; CC vs. AC + AA: OR=1.13, 95%CI=0.89-1.43, P-value=0.313; CC vs. AA: OR=1.17, 95%CI=0.90-1.51, P-value=0.239. Asian: C vs. A: OR=1.10, 95%CI=0.94-1.29, P-value=0.253; CC + AC vs. AA: OR=1.14, 95%CI=0.96-1.35, P-value=0.136; CC vs. AC + AA: OR=1.15, 95%CI=0.86-1.54, P-value=0.342; CC vs. AA: OR=1.23, 95%CI=0.86-1.76, P-value=0.265	MTHFR A1298C was significant associated with SZ.	Positive

Genes reported by this study for SZ/MDD

Disease	Gene	Description	Result Category
SZ	MTHFR	We conclude that MTHFR polymorphism is associated with SZ among Asian, African populations, but not the white.	Positive