No association between the Ser9Gly polymorphism of the dopamine receptor D3 gene and schizophrenia: a meta-analysis of family-based association studies

Abstract

Background: Ser9Gly (rs6280) is a functional single nucleotide polymorphism (SNP) in the human dopamine receptor D3 gene (DRD3). It is still controversial whether Ser9Gly is involved in the occurrence of schizophrenia. While there has been meta-analysis performed previously, that work did not include the family-based studies, which accounted for stratification bias. Thus, we performed a meta-analysis of family-based studies to explore the role of Ser9Gly in the etiology of schizophrenia. Methods: The published family-based association studies were retrieved from the relevant literature databases according to the established inclusion criteria. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to determine the strength of the relationship between Ser9Gly SNP and the occurrence of schizophrenia. Moreover, subgroup analysis was carried out by ethnicity (i.e., East Asian, Caucasian, and other populations). Results: We finally pooled up 13 family-based association studies between Ser9Gly SNP and schizophrenia. It contained 11 transmission disequilibrium test (TDT) studies with 1219 informative meiosis and 5 haplotype-based haplotype relative risk (HRR) studies. There was no statistical significance for the heterogeneity in TDT and HRR studies. Therefore, the fixed effect model was used to measure the pooled effect size. The results showed that this association was significantly protective in East Asian in TDT studies (204 informative meiosis, OR=0.744, 95% CI = 0.564-0.980, Z-value = -2.104, p = 0.035). Conclusions: Our meta-analysis found no association between DRD3 gene Ser9Gly polymorphism and the risk of schizophrenia. These data provide possible avenues for future family-based studies related to schizophrenia.