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A molecular Pathway Analysis Informs the Genetic Risk for Arrhythmia During Antipsychotic Treatment

Published online by Cambridge University Press:  23 March 2020

E.K. Fischer ,
H. Dyrby Andersen ,
M. Braun Jepsen  and
A. Drago
E.K. Fischer
Affiliation:
Psykiatrisk Forskningsenhed Vest, Forskningsenheden, Herning, Denmark
H. Dyrby Andersen
Affiliation:
Psykiatrisk Forskningsenhed Vest, Forskningsenheden, Herning, Denmark
M. Braun Jepsen
Affiliation:
Region Psykiatri Vest, Herning, Denmark
A. Drago
Affiliation:
Psykiatrisk Forskningsenhed Vest, Forskningsenheden, Herning, Denmark

Abstract

Background

Arrhythmia is a potentially fatal side effect of antipsychotics. A biologic predictive tool to prevent it is missing.

Aim

Identification of a genetic profile at risk for antipsychotic induced arrhythmia.

Objective

Identifying a molecular pathway enriched for antipsychotic induced QT-modifications.

Methods

Seven hundred and sixty-five SKZ individuals, M = 556, age = 40.93 ± 11.03 were included. QT-variation was a phase-specific created variable. A nested mixed regression served in R for clinical and molecular pathway analyses. Plink served for genetic analyses. Quality checking was standard, inflation factor was controlled by lambda values.

Results

Quetiapine and Perphenazine were associated with QT variation (P = 0.002; Estimate = 5.79 and P = 5.67e-06; Estimate = 8.96 respectively). No other significant association was detected. No inflation was detected. Axon guidance and Collagen biosynthesis (Table 1) were associated with QT variation at a conservative (adjusted) P value < 0.01.

Conclusions

Two molecular pathways were identified as possibly involved in QT modifications during antispsychotic treatment in SKZ patients. Previous evidence supports a role of the same pathways in cardiac disorders [1,2]. Interaction of specific SNPs with the drugs will be focus of further research.

Disclosure of interest

The authors have not supplied their declaration of competing interest.

Type
e-Poster walk: Genetics & molecular neurobiology and neuroscience in psychiatry
Information
European Psychiatry , Volume 41 , Issue S1: Abstract of the 25th European Congress of Psychiatry , April 2017 , pp. S164
Copyright
Copyright © European Psychiatric Association 2017

Table 1 Molecular pathways enriched in association with QT modifications.

References

Fukuda, K., et, H., et al.Cardiac Innervation and Sudden Cardiac Death. Circ Res 2015; 116: 2005–201910.1161/CIRCRESAHA.116.304679CrossRefGoogle ScholarPubMed
Lazzerini, P.E., et al.Connective tissue diseases and cardiac rhythm disorders: an overview. Autoimmun Rev 5 2006 306313[2005.11.002]10.1016/j.autrev.2005.11.002CrossRefGoogle ScholarPubMed
Figure 0

Table 1 Molecular pathways enriched in association with QT modifications.

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