Marlene Schouby Bentestuen - PhD Scholarship 2022
Project summary:
How do we prevent life-threatening drug-induced cardiac events?
In some individuals, commonly prescribed drugs cause an electrical disturbance in the heart known as QT prolongation. This electrical disturbance is an important risk factor for sudden cardiac death.
Pharmacogenetics (PGx) aims to use a patient's genetic information to predict treatment response and thereby reduce the risk of adverse events. Thus, a PGx testing tool could be central to optimized identification of patients at high risk of developing this serious cardiac event.
Project title
Pharmacogenetics in psychiatry: Optimizing identification of high-risk patients for the development of serious cardiac events
Background
QT prolongation is an important risk factor for malignant arrhythmias and sudden cardiac death. Several widely prescribed psychotropic drugs can cause this prolongation of ventricular repolarization (drug-induced long QT syndrome, diLQTS). Considering the inter-individual variability in drug response and the significant heritability of QT interval, a pharmacogenetic (PGx) testing tool could be central to optimization of identification of patients at high risk of diLQTS.
Aim
The overall aim of the project is to improve personalized medicine by reducing the risk of psychotropic diLQTS through optimized identification of high-risk patients for the development of serious cardiac side effects using PGx.
Further, we aim to improve the safety of psychopharmacotherapy, and increase our awareness and understanding of the complexity of cardiac side effects, drug-drug-gene interactions and genetics' role in psychotropic drug use.
Methods
To investigate the aim, three studies are planned:
- Investigation of current clinical prescription practice of QT prolonging drugs and interacting drugs in the Danish population.
- Investigation of candidate genes and polymorphisms for diLQTS in patients using psychotropic drugs.
- Development, application, and comparison of genetic risk scores for diLQTS.
The project is based on secondary use of existing data from Denmark (iPSYCH2015) and internationally from Estonian Biobank and UK Biobank.
Marlene Schouby Bentestuen
- MD
- Aarhus University, Department of Clinical Medicine & Aarhus University Hospital Psychiatry, Psychosis Research Unit
Main supervisor:
Associate Professor Christiane Gasse, Department of Clinical Medicine, Department of Affective Disorders and Psychosis Research Unit, Aarhus University & Aarhus University Hospital
Co-supervisors:
Professor Henrik Kjærulf Jensen, Department of Cardiology, Aarhus University Hospital
Associate Professor Alexander S. Hauser, Faculty of Health and Medical Sciences, UCPH
Professor Lili Milani, Estonian Genome Centre, University of Tartu, Estonia