title: Genome-wide association analysis to predict optimal antipsychotic dosage in schizophrenia: a pilot study.
abstract: In recent years, several studies have investigated genetic polymorphisms of antipsychotic drug-metabolizing enzymes and receptors. However, most studies focused on drug response and very few have investigated the genetic influence on antipsychotic dosage. The aim of the present study is to test the association between antipsychotic dosages at genome-wide level. The current dosage of antipsychotic medications was collected from 79 schizophrenia patients. The dosage was standardized using three different methods: chlorpromazine equivalent (CPZe), defined daily dose (DDD), and percentage of maximum dose (PM %). The patients were then genotyped using the Illumina HumanOmni2.5-8 BeadChip Kit. All markers were screened for significance using linear regression, and the p values were visualized using a Manhattan plot. The genome-wide analysis showed that the top Single-Nucleotide Polymorphisms (SNPs) associated with dosage variation were rs981975 on chromosome 14 for CPZe, rs4470690 on chromosome 4 for PM %, and rs79323383 on chromosome 8 for DDD. However, no genome-wide significantly associated SNPs were identified. In this pilot sample, we found promising trends for pharmacodynamic targets associated with antipsychotic dosage. Therefore, studies combining large prescription databases may identify genetic predictors to adjust the dose of antipsychotic medication.
authors.affiliation: Department of Psychiatry, University of Toronto, Toronto, Canada.|Universidade Federal de Ouro Preto, UFOP, Ouro Preto, Minas Gerais, Brazil.
authors.forename: Arthur T
authors.initials: AT
authors.lastname: Koga
authors.affiliation: Department of Psychiatry, University of Toronto, Toronto, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Strauss
authors.affiliation: Department of Psychiatry, University of Toronto, Toronto, Canada.
authors.forename: Clement
authors.initials: C
authors.lastname: Zai
authors.affiliation: Department of Psychiatry, University of Toronto, Toronto, Canada.
authors.forename: Gary
authors.initials: G
authors.lastname: Remington
authors.affiliation: Department of Psychiatry, University of Toronto, Toronto, Canada. vincenzo_deluca@camh.net.|EEG and Genetics Unit, Centre for Addiction and Mental Health, 250 College St, Toronto, ON, M5T 1R8, Canada. vincenzo_deluca@camh.net.|Department of Neuroscience, University of Naples 'Federico II', Naples, Italy. vincenzo_deluca@camh.net.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: De Luca
mesh_terms: D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000008:administration & dosage*; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics*; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents
keywords: Antipsychotics; CPZe; Defined daily dose; Genetics, GWAS; Schizophrenia
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