GENOME-WIDE ASSOCIATION STUDIES FOR ANTIPSYCHOTIC DRUGS

Genome-wide association studies (GWAS) have matured into a powerful tool to identify genetic variants that can be associated with various human phenotypes. GWAS for antipsychotic drugs (APD) are increasingly being performed to identify single nucleotide polymorphisms (SNPs) that affect therapeutic response and susceptibility to adverse drug reactions (ADRs). The aim of this study is to review the applications of GWAS to identify genetic variants associated with therapeutic response and ADR of APD. Systematic search of literatures using Medline (source PubMed) was made to identify published articles that included data for GWAS in APD. The prominent genetic variants identified for therapeutic response include polymorphisms in ARID5B, RTKN2, NPAS3 and PDE4D genes. For serious ADRs, polymorphisms in MC4R, MEIS2 and MMP16 genes for weight gain; polymorphisms in ZNF202, DPP6 and HSPG2 genes for extra-pyramidal side effects, and polymorphisms in SLC22A23, CERKL and SLCO3A1 genes for QT prolongation were reported among others. Large sample sizes and genotyping platforms with increased marker SNP density could provide greater confidence that important genetic variants could be discovered through GWAS, to advance clinical care with personalized medicine.