Study Report

Comment on Study

View All Comments on Study

Basic Info

Reference	Tan, E. C., 2004 PMID: 15564899
Citation	Tan, E. C., S. A. Chong, et al. (2004). "Genetic analysis of the thermolabile methylenetetrahydrofolate reductase variant in schizophrenia and mood disorders." Psychiatr Genet 14(4): 227-231.
Disease Type	Bipolar Disorder & Schizophrenia & Major Depressive Disorder
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	88 patients with unipolar depression, 167 patients with bipolar disorder, 236 patients with schizophrenia and 120 controls
SNP/Region/Marker Size	1 polymorphism
Predominant Ethnicity	Mongloid
Population	Chinese
Gender	179 males and 57 females with schizophrenia, 31 males and 57 females with unipolar disorder, 57 males and 110 females with bipolar disorder, 48 male and 72 female controls
Age Group	adults : 30-88 years (mean age=55.2, SD=10.3) of schizophrenia patients, 19-69 years (mean age=45, SD=11.5) of unipolar patients, 21-79 years (mean age=43.3, SD=14) of bipolar patients, 21-92 years (mean age=44.7, SD=16.3) of controls

Detail Info

Sample Diagnosis	DSM-IV
Sample Status	Diagnoses were made based on case records and clinical assessments by experienced psychiatrists according to DSM-IV criteria. Patients with other co-existing psychiatric diagnoses were excluded.
Technique	genotyping using PCR
Statistical Method	The distributions of genotypes for all groups were tested for deviation from Hardy-Weinberg equilibrium. Differences in genotype distribution and allele frequencies between groups were assessed by chi-squared analysis and Fisher's exact tests using S-PLUS, and subjects were stratified by psychiatric diagnosis and gender. Both dominant and recessive models were tested.
Result Summary	There was no significant difference in genotype distributions or allele frequencies between controls and any of the diagnostic groups, although the frequency of the T allele was higher for all diagnostic groups and for both the male and female genders. When data was analyzed with the minor T allele as dominant, there was an excess of the T-containing genotypes in each of the patient groups compared with controls. For the difference between controls and all cases combined it almost reached statistical significance (P=0.077), with an odds ratio of 1.46 (95% confidence interval, 0.96-2.22). Although there was no significant association as measured by the P value, the odds ratio and confidence interval provided some evidence of increased risk for individuals with the T-containing genotypes. A minor role for this polymorphism in the pathogenesis of schizophrenia and depression could not be ruled out and would warrant further investigation.

Genetic factors reported by this study for BD

Other variants reported by this study for BD (count: 1)

Variant Name	Related Gene	Type	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
MTHFR C677T	MTHFR	point mutation	C>T		genotypic P-value = 0.230, X²=2.944, allelic P-value = 0.441, X²=0.594 in females with bipolar; genotypic P-value = 0.820, X²=0.398, allelic P-value = 0.546, X²=0.365 in males with bipolar; genotypic P-value = 0.104, X²=4.519, allelic P-value = 0.301, X²=1.069 in all female patients with bipolar; genotypic P-value = 0.700, X²=0.715, allelic P-value = 0.431, X²=0.619 in all male patients with bipolar. X²==3.119, d.f.=1, P=0.077, OR=1.46, 95% confidence interval=0.96-2.22 between controls and all psychiatric cases combined in the dominant model.	For bipolar disorder, there was also no difference for both ...... For bipolar disorder, there was also no difference for both genotype and allele frequencies. The level of significance as measured by the P value did not improve even when data was stratified according to gender. When patients from all the three diagnostic group were combined and analyzed against the controls, there was no significant difference in terms of genotype and allele frequencies for males. With the female group, there was improvement in the level of significance for difference in genotype distribution between controls and all patients. In the dominant model, there was marginally significant difference between controls and and all psychiatric cases combined. More...	Negative

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

Gene	Statistical Values/Author Comments	Result Category
MTHFR	There was no significant difference in genotype distributions or allele frequencies of the MTHFR 667...... There was no significant difference in genotype distributions or allele frequencies of the MTHFR 667C>T polymorphism between controls and any of the diagnostic groups. More...	Negative

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 C677T	MTHFR	point mutation	genotypic P-value = 0.268, X²=2.636, allelic P-value = 0.345, X²=0.893 in females with schizophrenia; genotypic P-value = 0.731, X²=0.628, allelic P-value = 0.509, X²=0.437 in males with schizophrenia; genotypic P-value = 0.104, X²=4.519, allelic P-value = 0.301, X²=1.069 in all female patients with schizophrenia; genotypic P-value = 0.700, X²=0.715, allelic P-value = 0.431, X²=0.619 in all males patients with schizophrenia; X²=2.724, d.f.=1, P-value = 0.099, OR=1.47 95% confidence interval=0.93-2.33 between controls and patients with schizophrenia; X²==3.119, d.f.=1, P=0.077, OR=1.46, 95% confidence interval=0.96-2.22 between controls and all psychiatric cases combined in the dominant model	Genotype and allele frequencies between controls and patients with schizophrenia were similar. When subjects were stratified according to gender, the difference in terms of P value remained insignificant for both males and females. When patients from all the three diagnostic group were combined and analyzed against the controls, there was no significant difference in terms of genotype and allele frequencies for males. With the female group, there was improvement in the level of significance for difference in genotype distribution between controls and all patients. In the dominant model, there was marginally significant difference between controls and patients with schizophrenia and and all psychiatric cases combined.	Negative
MDD	MTHFR C677T	MTHFR	point mutation	genotypic P-value = 0.111, X²=4.406, allelic P-value = 0.345, X²=0.893 in females with unipolar; genotypic P-value = 0.545, X²=1.216, allelic P-value = 0.308, X²=1.038 in males with unipolar; genotypic P-value = 0.104, X²=4.519, allelic P-value = 0.301, X²=1.069 in all female patients with unipolar; genotypic P-value = 0.700, X²=0.715, allelic P-value = 0.431, X²=0.619 in all males patients with unipolar. X²==3.119, d.f.=1, P=0.077, OR=1.46, 95% confidence interval=0.96-2.22 between controls and all psychiatric cases combined in the dominant model.	The difference between control and unipolar depressive patients was not significant at the genotype level or the allelic level. When the data were analyzed separately for each gender, only the female group showed improved statistical significance for genotype distribution. When patients from all the three diagnostic group were combined and analyzed against the controls, there was no significant difference in terms of genotype and allele frequencies for males. With the female group, there was improvement in the level of significance for difference in genotype distribution between controls and all patients. In the dominant model, there was marginally significant difference between controls and and all psychiatric cases combined.	Negative

Genes reported by this study for SZ/MDD

Disease	Gene	Description	Result Category
SZ	MTHFR	There was no significant difference in genotype distributions or allele frequencies of the MTHFR 667C>T polymorphism between controls and any of the diagnostic groups.	Negative
MDD	MTHFR	There was no significant difference in genotype distributions or allele frequencies of the MTHFR 667C>T polymorphism between controls and any of the diagnostic groups.	Negative