Cardiac Genetics

I am highly involved in research in the field of genetic causes of cardiac arrhythmia. My main project uses Next Generation Sequencing to perform genetic screening of approximately 1000 atrial fibrillation patients with early onset of lone atrial fibrillation (lone AF) and 25 families with an accumulation of atrial fibrillation (AF), in order to identify genetic variations as a cause of AF. The 25 families has already been exome Sequencing and we are currently analyzing the huge amount data.

What is our hypothesis?

In patients with early onset lone AF and in families with an accumulation of AF, we can detect genetic variations associated with the disease. These variations alter the function of the cardiac myocytes and thus play a role in the pathophysiology of AF.

What is Atrial Fibrillation (AF)?

In the normal heart the electrical impulses are generated by the sinoatrial node, and through the atrioventricular node these impulses are conducted to the ventricles where they spread to form regular and controlled contractions generating the heartbeat (figure 1). In AF the normal electrical impulses in the atria have been exchanged by fast and chaotic impulses, leading to irregular conduction to the ventricles often resulting in a fast and irregular heart rhythm (figure 1).

Why is AF an important area of interest?

AF is the most common treatment required arrhythmia and approximately one in twenty Danes above the age of 65 are affected. Each year 1-2 % of the population are affected by AF, and thereby causing approximately 15.000 hospital admissions per year in Denmark. The prevalence of AF is increasing and is expected to be doubled within the next 30 years.

Exploring the genetics of AF

Genes are the hereditary units of the DNA, and are the genomic areas where the proteins are encoded. All proteins are encoded by specific genes, and if a change (gene-variation) occurs in a gene it sometimes results in a change of the function of the corresponding protein, which potentially could cause disease.

Next Generation Sequencing

For many years the gold-standard method of gene sequencing has been the Sanger sequencing method where one had to select candidate genes that were subsequently analyzed one by one. A method that could easily take months before the results of just a single gene were available. Within the last years, technology in genetic sequencing has evolved greatly, resulting in a plethora of new techniques, collectively named Next Generation Sequencing. With next generation sequencing the entire DNA (genome) or major parts of it (e.g. all protein coding regions = the exome) can be analyzed in just one analysis and requiring only a few days to obtain the results.

The perspective of the project

Today there is only very few effective pharmacological treatment options for AF, and unfortunately there are many side effects to the drugs and especially the risk of proarrhythmia is feared. As long as the understanding of mechanisms of AF is still limited the development of new treatments are challenging. Identifying the underlying pathophysiology of AF generates new knowledge which can be used to better the search for new and better treatments for AF.