Gene polymorphisms of DISC1 is associated with schizophrenia: Evidence from a meta-analysis

Previous studies suggest an association between Disrupted in schizophrenia 1 (DISC1) polymorphisms and schizophrenia (SCZ). However, the available data are often inconsistent, regarding the difference in sample size, ethnicity, genotyping method, etc. Thus, we carried out a meta-analysis to determine whether DISC1 polymorphisms contributed susceptibility to SCZ.

A methodical literature review was operated using the English and Chinese core electronic databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were applied to determine the correlation between DISC1 gene polymorphisms and SCZ susceptibility. Subgroup analyses were carried out by stratification of ethnicity. P values were Bonferroni adjusted to account for multiple testing. Publication bias was evaluated by funnel plots, Egger's test and the trim and fill method.

Meta-analyses results suggested that DISC1 polymorphisms (rs821616 and rs821597) increased SCZ risk in overall populations. In subgroups of ethnicity, DISC1 polymorphisms (rs821616 and rs821597) was associated with susceptibility to SCZ among the Chinese population (for rs821616: TT+AT vs. AA: OR=1.338, 95% CI=1.124-1.592, P=0.001; T vs. A: OR=1.300, 95% CI=1.124-1.504, P<0.000; for rs821597: AA+AG vs. GG: OR=1.508, 95% CI=1.268-1.794, P<0.001; A vs. G: OR=1.345, 95% CI=1.184-1.527, P<0.001). A positive correlation was also observed between the single marker rs821616 and SCZ among the Japanese population in the recessive model (TT vs. AT+AA: OR=1.524, 95% CI=1.185-1.959, P=0.001). There was no significant relationship between other DISC1 polymorphisms (rs3738401, rs2273890, rs3738398, rs3738402, rs2492367, rs843979, rs3737597, rs4658971, rs1538979, rs1000731 and rs3738399) and SCZ.

DISC1 polymorphisms increased a risk of SCZ, especially in the Chinese population. In order to further corroborate our findings, large well-designed epidemiological studies are needed.