Dopamine genes and schizophrenia: case closed or evidence pending?

Schizophr Bull. 2007 Sep;33(5):1071-81. doi: 10.1093/schbul/sbm076. Epub 2007 Jul 14.

Abstract

The dopamine hypothesis of schizophrenia (SZ) has motivated a large number of genetic association studies but few if any dopaminergic (DA) polymorphisms are accepted as credible risk factors at present. To evaluate whether dopamine-related genes have been investigated adequately, we surveyed public genetic databases and published SZ association studies with regard to 14 conventional DA genes and 7 selected dopamine-interacting proteins. We estimate that 325 polymorphisms would be required to evaluate the impact of common variation on SZ risk among Caucasian samples. To date, 98 polymorphisms have been analyzed in published association studies. We estimate that only 19 of these variations have been evaluated in samples with at least 50% power to detect an association of the effect size commonly found in genetically complex disorders. While it is possible that DA genes do not harbor genetic risk factors for SZ, our review suggests that satisfactory conclusions for most genes cannot be drawn at present. Whole-genome association studies have begun to fill this void, but additional analyses are likely to be needed. Recommendations for future association studies include analysis of adequately powered samples, judiciously selected polymorphisms, multiple ethnic groups, and concurrent evaluation of function at associated single-nucleotide polymorphisms.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Brain / physiopathology
  • Case-Control Studies
  • Chromosome Mapping
  • Databases, Genetic
  • Dopamine / genetics*
  • Dopamine / physiology
  • Genetic Linkage
  • Genotype
  • Humans
  • Polymorphism, Genetic* / genetics
  • Polymorphism, Single Nucleotide / genetics
  • Risk Factors
  • Schizophrenia / genetics*
  • Schizophrenia / physiopathology
  • White People / genetics

Substances

  • Dopamine