Atrial Fibrillation (AF) is a deadly and common arrhythmia that affects more than 30 million individuals worldwide. The disease may lead to heart failure, stroke, dementia and premature death. It may occur in all ages, but in particular in elderly individuals with accumulating co-morbidity. In the last two decades, we have discovered many genetic regions associated with this polygenetic arrhythmia. Individuals who perform extensive endurance training have increased risk of developing AF, of reasons not known. Many genetic loci have been associated with physical activity, but no genetic causes of exercise-associated AF have thus far been identified.

Standardbred trotter horses are one of the few types of mammals who, as humans, develop spontaneous AF. It has been shown that Standardbred and Thoroughbred horses may serve as well-functioning models to test potential new drugs to treat AF and to study cardiovascular hemodynamics during ongoing AF. Standardbred and Thoroughbred trotter horses are bred for the purpose of performing well in high-intensity running, making them a good model for exercise-associated AF. The fact that they undergo strict breeding also makes them an ideal population for genetic studies, due to less genetic variation and thus a need for fewer cases and controls to identify common variants linked with disease. Genome-wide association studies (GWAS) have been performed in several horse case-control populations and have identified genetic loci associated with recurrent airway obstruction, immune-mediated myositis, and body weight. In the current proposal, we aim to take advantage of a cross-species model for genetic analysis. We will I) identify genetic causes of exercise-induced AF, by performing genome-wide association studies (GWAS) in a horse AF case-control population, followed by II) replication in a second horse population and finally III) replication in a human cross-country skier population consisting of AF cases and healthy referents. The project involves international collaborators from Australia and Denmark.