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A molecular pathway analysis informs the genetic risk for arrhythmias during antipsychotic treatment

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A molecular pathway analysis informs the genetic risk for arrhythmias during antipsychotic treatment. / Drago, Antonio; Fischer, Ellen Kure.

I: International Clinical Psychopharmacology, Bind 33, Nr. 1, 01.01.2018, s. 1-14.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

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Drago, Antonio ; Fischer, Ellen Kure. / A molecular pathway analysis informs the genetic risk for arrhythmias during antipsychotic treatment. I: International Clinical Psychopharmacology. 2018 ; Bind 33, Nr. 1. s. 1-14.

Bibtex

@article{c591e54183ad42829fb0f5a4b4202fd4,
title = "A molecular pathway analysis informs the genetic risk for arrhythmias during antipsychotic treatment",
abstract = "Arrhythmias are a frequent and potentially fatal side effect of antipsychotic treatment. Strict ECG monitoring and clinical interviews are the standards used to prevent arrhythmias. A biologic predictive tool is missing. The identification of a genetic makeup at risk of antipsychotic-induced arrhythmias is the aim of the present investigation. The aim of this study was to identify a molecular pathway enriched in single nucleotide polymorphisms associated with antipsychotic-induced QTc modifications. In total, 661 schizophrenic individuals from the CATIE study, M=486 (73.52%), mean age=40.92±11.02, were included. QTc variation was measured as a phase-specific change-created variable. A nested mixed regression for a repeated-measures model served in R for the analysis of the clinical and treatment-related covariates and molecular pathway analysis. Plink was used for the genetic genome-wide analysis. Quality checking was the standard (genotype call rate>0.95; minor allele frequency>0.01; Hardy-Weinberg equilibrium<0.0001) and the inflation factor was controlled by λ values. Quetiapine and perphenazine were associated with QTc variation during phase 1. No other significant association was detected. No significant inflation was detected. A number of molecular pathways were associated with QT variation at a conservative (adjusted) P value less than 0.05, including pathways related to neuronal wiring and collagen biosynthesis, along with pathways related to K+ currents and cardiac contraction. Pathways related to neuronal wiring, collagen biosynthesis, and ion currents were identified as possibly involved in QTc modifications during antispsychotic treatment in SKZ patients.",
keywords = "arrhythmias, cardiac side effects, genome-wide, molecular pathway analysis, schizophrenia",
author = "Antonio Drago and Fischer, {Ellen Kure}",
year = "2018",
month = jan,
day = "1",
doi = "10.1097/YIC.0000000000000198",
language = "English",
volume = "33",
pages = "1--14",
journal = "International Clinical Psychopharmacology",
issn = "0268-1315",
publisher = "Lippincott Williams & Wilkins, Ltd.",
number = "1",

}

RIS

TY - JOUR

T1 - A molecular pathway analysis informs the genetic risk for arrhythmias during antipsychotic treatment

AU - Drago, Antonio

AU - Fischer, Ellen Kure

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Arrhythmias are a frequent and potentially fatal side effect of antipsychotic treatment. Strict ECG monitoring and clinical interviews are the standards used to prevent arrhythmias. A biologic predictive tool is missing. The identification of a genetic makeup at risk of antipsychotic-induced arrhythmias is the aim of the present investigation. The aim of this study was to identify a molecular pathway enriched in single nucleotide polymorphisms associated with antipsychotic-induced QTc modifications. In total, 661 schizophrenic individuals from the CATIE study, M=486 (73.52%), mean age=40.92±11.02, were included. QTc variation was measured as a phase-specific change-created variable. A nested mixed regression for a repeated-measures model served in R for the analysis of the clinical and treatment-related covariates and molecular pathway analysis. Plink was used for the genetic genome-wide analysis. Quality checking was the standard (genotype call rate>0.95; minor allele frequency>0.01; Hardy-Weinberg equilibrium<0.0001) and the inflation factor was controlled by λ values. Quetiapine and perphenazine were associated with QTc variation during phase 1. No other significant association was detected. No significant inflation was detected. A number of molecular pathways were associated with QT variation at a conservative (adjusted) P value less than 0.05, including pathways related to neuronal wiring and collagen biosynthesis, along with pathways related to K+ currents and cardiac contraction. Pathways related to neuronal wiring, collagen biosynthesis, and ion currents were identified as possibly involved in QTc modifications during antispsychotic treatment in SKZ patients.

AB - Arrhythmias are a frequent and potentially fatal side effect of antipsychotic treatment. Strict ECG monitoring and clinical interviews are the standards used to prevent arrhythmias. A biologic predictive tool is missing. The identification of a genetic makeup at risk of antipsychotic-induced arrhythmias is the aim of the present investigation. The aim of this study was to identify a molecular pathway enriched in single nucleotide polymorphisms associated with antipsychotic-induced QTc modifications. In total, 661 schizophrenic individuals from the CATIE study, M=486 (73.52%), mean age=40.92±11.02, were included. QTc variation was measured as a phase-specific change-created variable. A nested mixed regression for a repeated-measures model served in R for the analysis of the clinical and treatment-related covariates and molecular pathway analysis. Plink was used for the genetic genome-wide analysis. Quality checking was the standard (genotype call rate>0.95; minor allele frequency>0.01; Hardy-Weinberg equilibrium<0.0001) and the inflation factor was controlled by λ values. Quetiapine and perphenazine were associated with QTc variation during phase 1. No other significant association was detected. No significant inflation was detected. A number of molecular pathways were associated with QT variation at a conservative (adjusted) P value less than 0.05, including pathways related to neuronal wiring and collagen biosynthesis, along with pathways related to K+ currents and cardiac contraction. Pathways related to neuronal wiring, collagen biosynthesis, and ion currents were identified as possibly involved in QTc modifications during antispsychotic treatment in SKZ patients.

KW - arrhythmias

KW - cardiac side effects

KW - genome-wide

KW - molecular pathway analysis

KW - schizophrenia

UR - http://www.scopus.com/inward/record.url?scp=85037078609&partnerID=8YFLogxK

U2 - 10.1097/YIC.0000000000000198

DO - 10.1097/YIC.0000000000000198

M3 - Journal article

C2 - 29064910

AN - SCOPUS:85037078609

VL - 33

SP - 1

EP - 14

JO - International Clinical Psychopharmacology

JF - International Clinical Psychopharmacology

SN - 0268-1315

IS - 1

ER -