title: Polygenic risk score prediction of antipsychotic dosage in schizophrenia.
abstract: OBJECTIVE
  Genetic variants have yet to be identified as reliable predictors of antipsychotic dosage. The purpose of this study is to quantify significant genetic risk variants prioritized from the Psychiatric GWAS Consortium (PGC2) study for schizophrenia as a polygenic score to test our hypothesis that it may represent symptom severity in patients and therefore predict antipsychotic dosage.
  
  
  METHODS
  Antipsychotic medication and dosage were collected in our sample of 83 patients with schizophrenia spectrum disorders of a homogeneous European background. Antipsychotic dosage was standardized according to the Product Monograph (PM%), chlorpromazine equivalents (CPZe), and Defined Daily Dose (DDD). We calculated polygenic risk scores (PRS) for the significant risk loci identified from the PGC2 GWAS to predict dosage using a linear regression model.
  
  
  RESULTS
  In our analysis, the PRS showed no significant association with PM%, CPZe, and DDD dosage. Considering symptom severity and overall functioning, our PRS was similarly not significantly associated with Global Assessment of Functioning (GAF) scores.
  
  
  CONCLUSIONS
  Our results do not provide evidence for a polygenic inheritance of schizophrenia that influences levels of antipsychotic dosage. To the best of our knowledge, this is one of the first studies of its kind to use the PRS from the PGC2 significant risk variants to predict a clinically relevant phenotype. The PRS offers a novel approach to analyzing the genetic liability for many clinically relevant phenotypes in schizophrenia.
authors.affiliation: Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; EEG and Genetics Unit, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario M5T 1R8, Canada.
authors.forename: Nuwan C
authors.initials: NC
authors.lastname: Hettige
authors.affiliation: Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; University of Ottawa, 75 Laurier Ave E, Ottawa, ON K1N 6N5, Canada.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Cole
authors.affiliation: EEG and Genetics Unit, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario M5T 1R8, Canada.
authors.forename: Sarah
authors.initials: S
authors.lastname: Khalid
authors.affiliation: Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; EEG and Genetics Unit, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario M5T 1R8, Canada; Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario M5T 1R8, Canada. Electronic address: vincenzo_deluca@camh.net.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: De Luca
mesh_terms: D000483:Alleles; D014150:Antipsychotic Agents / Q000008:administration & dosage*; D002746:Chlorpromazine / Q000008:administration & dosage; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D007406:Interview, Psychological; D008297:Male; D008875:Middle Aged; D020412:Multifactorial Inheritance; D011618:Psychotic Disorders / Q000188:drug therapy / Q000235:genetics; D018570:Risk Assessment; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics*; D012720:Severity of Illness Index; D044465:White People
chemical_list: D014150:Antipsychotic Agents; D002746:Chlorpromazine
keywords: Antipsychotic dosage; Chlorpromazine equivalents; Defined daily dose; Polygenic risk score; Schizophrenia