title: Association of orexin receptor polymorphisms with antipsychotic-induced weight gain.
abstract: Antipsychotic-induced weight gain (AIWG) is a common side effect of treatment with antipsychotics such as clozapine and olanzapine. The orexin gene and its receptors are expressed in the hypothalamus and have been associated with maintenance of energy homeostasis. In this study, we have analysed tagging single nucleotide polymorphisms (SNPs) in orexin receptors 1 and 2 (HCRTR1 and HCRTR2) for association with AIWG.
  
  
  
  Schizophrenia or schizoaffective disorder subjects (n = 218), treated mostly with clozapine and olanzapine for up to 14 weeks, were included. Replication was conducted in a subset of CATIE samples (n = 122) treated with either olanzapine or risperidone for up to 190 days. Association between SNPs and AIWG was assessed using analysis of covariance (ANCOVA) with baseline weight and duration of treatment as covariates.
  
  
  
  Several SNPs in HCRTR2 were nominally associated with AIWG in patients of European ancestry treated with either clozapine or olanzapine (P<0.05). In the replication analysis two SNPs rs3134701 (P = 0.043) and rs12662510 (P = 0.012) were nominally associated with AIWG. None of the SNPs in HCRTR1 were associated with AIWG.
  
  
  
  This study provides preliminary evidence supporting the role of HCRTR2 in AIWG. However, these results need to be confirmed in large study samples.
authors.affiliation: a Pharmacogenetics Research Clinic, Neurogenetics Section , Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health , Toronto , ON , Canada .
authors.forename: Arun K
authors.initials: AK
authors.lastname: Tiwari
authors.affiliation: a Pharmacogenetics Research Clinic, Neurogenetics Section , Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health , Toronto , ON , Canada .|b Department of Psychiatry and Psychotherapy, Campus Mitte , Charité Universitätsmedizin Berlin , Berlin , Germany .
authors.forename: Eva J
authors.initials: EJ
authors.lastname: Brandl
authors.affiliation: a Pharmacogenetics Research Clinic, Neurogenetics Section , Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health , Toronto , ON , Canada .|c Department of Psychiatry , University of Toronto , Toronto , ON , Canada .
authors.forename: Clement C
authors.initials: CC
authors.lastname: Zai
authors.affiliation: a Pharmacogenetics Research Clinic, Neurogenetics Section , Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health , Toronto , ON , Canada .
authors.forename: Vanessa F
authors.initials: VF
authors.lastname: Goncalves
authors.affiliation: a Pharmacogenetics Research Clinic, Neurogenetics Section , Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health , Toronto , ON , Canada .
authors.forename: Nabilah I
authors.initials: NI
authors.lastname: Chowdhury
authors.affiliation: a Pharmacogenetics Research Clinic, Neurogenetics Section , Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health , Toronto , ON , Canada .
authors.forename: Natalie
authors.initials: N
authors.lastname: Freeman
authors.affiliation: d Department of Psychiatry, College of Physicians and Surgeons , Columbia University and the New York State Psychiatric Institute , New York City , NY , USA , and.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Lieberman
authors.affiliation: e Department of Psychiatry and Behavioural Sciences , Northwestern University , Chicago , IL , USA.
authors.forename: Herbert Y
authors.initials: HY
authors.lastname: Meltzer
authors.affiliation: a Pharmacogenetics Research Clinic, Neurogenetics Section , Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health , Toronto , ON , Canada .
authors.forename: James L
authors.initials: JL
authors.lastname: Kennedy
authors.affiliation: a Pharmacogenetics Research Clinic, Neurogenetics Section , Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health , Toronto , ON , Canada .|c Department of Psychiatry , University of Toronto , Toronto , ON , Canada .
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Müller
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects*; D001569:Benzodiazepines / Q000009:adverse effects; D003024:Clozapine / Q000009:adverse effects; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D064446:Orexin Receptors / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D018967:Risperidone / Q000009:adverse effects; D012559:Schizophrenia / Q000188:drug therapy*; D014481:United States; D015430:Weight Gain; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; C578630:HCRTR1 protein, human; C578626:HCRTR2 protein, human; D064446:Orexin Receptors; D001569:Benzodiazepines; D003024:Clozapine; D018967:Risperidone; D000077152:Olanzapine
keywords: HCRTR2; antipsychotics; clozapine; pharmacogenetics; weight gain