Brain-derived neurotrophic factor gene polymorphisms and schizophrenia: a meta-analysis.

Objectives: To evaluate whether the G196A and C270T polymorphisms of the brain-derived neurotrophic factor gene are associated with increased risk of schizophrenia.

Methods: A meta-analysis of nine genetic association studies was carried out. The meta-analysis included genotype data on 1404/1597 schizophrenics/controls for G196A and 877/989 schizophrenics/controls for C270T.

Results: The overall analysis for investigating the association of the G196A allele G and the risk of developing schizophrenia relative to the allele A, showed significant evidence of heterogeneity (P=0.05, I(2)=58%) between the studies and nonsignificant association [random effects odds ratio 1.08 and 95% confidence interval (0.88-1.32)]. In Caucasians, there was a trend towards heterogeneity (P=0.19, I(2)=40%), then, the random and fixed effects odds ratios were 1.24 (0.96-1.60) and 1.27 (1.06-1.53), respectively. For the C270T polymorphism, overall, there was significant evidence of heterogeneity between studies (P=0.07, I(2)=55%) and the allele T was associated with a 63% increased risk of schizophrenia compared with C allele [random effects odds ratio 1.63 (1.01-2.65)]. The dominant model for allele T produced significant association [random effects odds ratio 1.68 (1.02-2.79)]. No source of bias was seen in the selected studies and the differential magnitude of effect in large versus small studies was not significant.

Conclusions: The meta-analysis results provided a weak evidence of association between C270T polymorphism and schizophrenia, and large heterogeneity between studies, whereas there was no evidence of association for G196A polymorphism. The above findings reinforce the need for large and more rigorous association studies.