PMID- 26778674
OWN - NLM
STAT- MEDLINE
DCOM- 20161213
LR  - 20221207
IS  - 1573-2509 (Electronic)
IS  - 0920-9964 (Linking)
VI  - 170
IP  - 2-3
DP  - 2016 Feb
TI  - Polygenic risk score prediction of antipsychotic dosage in schizophrenia.
PG  - 265-70
LID - S0920-9964(15)30087-6 [pii]
LID - 10.1016/j.schres.2015.12.015 [doi]
AB  - 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. DISCUSSION: 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.
CI  - Copyright (c) 2015 Elsevier B.V. All rights reserved.
FAU - Hettige, Nuwan C
AU  - Hettige NC
AD  - 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.
FAU - Cole, Christopher B
AU  - Cole CB
AD  - Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; 
      University of Ottawa, 75 Laurier Ave E, Ottawa, ON K1N 6N5, Canada.
FAU - Khalid, Sarah
AU  - Khalid S
AD  - EEG and Genetics Unit, Centre for Addiction and Mental Health, 250 College 
      Street, Toronto, Ontario M5T 1R8, Canada.
FAU - De Luca, Vincenzo
AU  - De Luca V
AD  - 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.
LA  - eng
GR  - Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160108
PL  - Netherlands
TA  - Schizophr Res
JT  - Schizophrenia research
JID - 8804207
RN  - 0 (Antipsychotic Agents)
RN  - U42B7VYA4P (Chlorpromazine)
SB  - IM
MH  - Alleles
MH  - Antipsychotic Agents/*administration & dosage
MH  - Chlorpromazine/administration & dosage
MH  - Female
MH  - Genetic Loci
MH  - *Genetic Predisposition to Disease
MH  - Genetic Variation
MH  - Humans
MH  - Interview, Psychological
MH  - Male
MH  - Middle Aged
MH  - *Multifactorial Inheritance
MH  - Psychotic Disorders/drug therapy/genetics
MH  - Risk Assessment
MH  - Schizophrenia/*drug therapy/*genetics
MH  - Severity of Illness Index
MH  - White People
OTO - NOTNLM
OT  - Antipsychotic dosage
OT  - Chlorpromazine equivalents
OT  - Defined daily dose
OT  - Polygenic risk score
OT  - Schizophrenia
EDAT- 2016/01/19 06:00
MHDA- 2016/12/15 06:00
CRDT- 2016/01/19 06:00
PHST- 2015/08/19 00:00 [received]
PHST- 2015/12/17 00:00 [revised]
PHST- 2015/12/22 00:00 [accepted]
PHST- 2016/01/19 06:00 [entrez]
PHST- 2016/01/19 06:00 [pubmed]
PHST- 2016/12/15 06:00 [medline]
AID - S0920-9964(15)30087-6 [pii]
AID - 10.1016/j.schres.2015.12.015 [doi]
PST - ppublish
SO  - Schizophr Res. 2016 Feb;170(2-3):265-70. doi: 10.1016/j.schres.2015.12.015. Epub 
      2016 Jan 8.