A Novel DRD2 Single-Nucleotide Polymorphism Associated with Schizophrenia Predicts Age of Onset: HapMap Tag-Single-Nucleotide Polymorphism Analysis

Background: Dopamine D2 receptor (DRD2) is thought to be critical in regulating the dopaminergic pathway in the brain, which is known to be important in the etiology of schizophrenia. It is, therefore, not surprising that most antipsychotic medication acts on DRD2. DRD2 is widely expressed in the brain; levels are reduced in the brains of patients with schizophrenia, and DRD2 polymorphisms have been associated with reduced brain expression. We have previously identified a genetic variant in DRD2, rs6277 to be strongly implicated in schizophrenia susceptibility. Methods: To identity new associations in the DRD2 gene with disease status and clinical severity, we genotyped seven single-nucleotide polymorphisms (SNPs) in DRD2 by using a multiplex mass spectrometry method. SNPs were chosen by using a haplotype block-based gene-tagging approach; so, the entire DRD2 gene was represented. Results: One polymorphism, rs2734839 was found to be significantly associated with schizophrenia as well as late onset age. Individuals carrying the genetic variation were more than twice as likely to have schizophrenia compared with controls. Conclusions: Our results suggest that DRD2 genetic variation is a good indicator for schizophrenia risk and may also be used as a predictor of age of onset.