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

Psychiatr Genet. 2003 Mar;13(1):1-12. doi: 10.1097/00041444-200303000-00001.


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 Ser9Gly 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 Ser9Gly homozygosity and schizophrenia ( =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 (chi2 =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.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Substitution*
  • Case-Control Studies
  • Genetic Variation*
  • Glycine
  • Homozygote
  • Humans
  • Receptors, Dopamine D2 / genetics*
  • Receptors, Dopamine D3
  • Reference Values
  • Schizophrenia / genetics*
  • Serine
  • Sweden


  • DRD3 protein, human
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Serine
  • Glycine