Preliminary evidence for association of genome-wide significant DRD2 schizophrenia risk variant with clozapine response

Pharmacogenomics. 2016;17(2):103-9. doi: 10.2217/pgs.15.155. Epub 2015 Dec 15.

Abstract

Aim: The recent Psychiatric Genomics Consortium genome-wide association study identified an SNP, rs2514218, located 47kb upstream of the DRD2 gene to be associated with risk for schizophrenia (p = 2.75e-11). Since all antipsychotics bind to dopamine D2 receptors, we examined rs2514218 in relation to response to antipsychotic treatment.

Patients & methods: We investigated the SNP in relation to treatment response in a prospective study consisting of 208 patients (151 Caucasians, 42 African-Americans and 15 others) treated with clozapine for 6 months.

Results: rs2514218 was associated with total score change in the brief psychiatric rating scale under an additive model (pcorr= 0.033).

Conclusion: Our finding provides evidence for rs2514218 association with antipsychotic response, but further replication is required before firm conclusions can be drawn.

Keywords: antipsychotic; clinical response; clozapine; dopamine D2 receptor; genetics; pharmacogenetics; schizophrenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antipsychotic Agents / therapeutic use*
  • Clozapine / therapeutic use*
  • Female
  • Genetic Association Studies
  • Humans
  • Male
  • Polymorphism, Single Nucleotide
  • Receptors, Dopamine D2 / genetics*
  • Risk
  • Schizophrenia / drug therapy
  • Schizophrenia / genetics*

Substances

  • Antipsychotic Agents
  • DRD2 protein, human
  • Receptors, Dopamine D2
  • Clozapine