Dopamine D3 receptor gene Ser9Gly variant and schizophrenia:: association study and meta-analysis

Objective To further evaluate the controversial putative association between a Ser9Gly variant in the first exon of the dopamine D3 receptor gene (DRD3) and schizophrenia. Methods Swedish patients with schizophrenia (n=156) and control subjects (n=463) were assessed for the DRD3 Ser9Gly variant. Meta-analyses including previous and the present Swedish case-control results were performed. Results No significant difference between the Swedish patients and controls were found, but there was an association between DRD3 Ser9GIy Ser/Ser and homozygous genotypes and response to anti-psychotic drugs. This finding was supported by an incomplete meta-analysis. In a meta-analysis of all case-control studies comprising 8761 subjects the association between DRD3 Ser9GIy homozygosity and schizophrenia (chi(2) =4.96, degree of freedom = 1, p < 0.05, odds ratio = 1.10, 95% confidence interval = 1.01-1.20) persisted. However, the previously proposed association between the Ser/Ser genotype and schizophrenia was not significant (chi(2) = 2.71, degree of freedom= 1, p > 0.05, odds ratio= 1.08, 95% confidence interval= 0.99-1.17). Conclusions Whereas the present Swedish case-control analysis did not yield any evidence for association with the diagnosis, the present meta-analysis suggests that the DRD3 gene confer susceptibility to schizophrenia. Reasons for the discrepancies between prior studies are discussed. Psychiatr Genet 13:1-12 (C) 2003 Lippincott Williams Wilkins.