Drosophila Modeling Identifies Increased Sleep as a Link Between Insomnia and Cardiovascular Disease

Insomnia is a common sleep disorder associated with negative long-term health outcomes. Mendelian randomization studies have found that insomnia significantly increases the risk of cardiovascular disease (CVD). To better understand the link between sleep and heart health, we identify genes associated with both insomnia and CVD. We model the disruption of the Drosophila melanogaster orthologs in neurons and cardiac tissue to characterize their cell-autonomous and non-cell-autonomous role in regulating sleep and cardiac physiology. We identify three genes that function in neurons and the heart to cell-autonomously regulate the function of each tissue. We find that the disruption of insomnia- and CVD-associated Drosophila orthologs in the heart most often lead to increased nighttime sleep. Inversely, disruptions in neurons that lead to increased sleep most often result in an elevated heart rate. To confirm the association between increased sleep and cardiac function, we performed a genetic correlation analysis from human data between long sleep-related traits and adverse cardiac outcomes. Significant correlations were found between most long sleep traits and heart failure, coronary artery disease, or myocardial infarction, reinforcing our findings in the fly linking increased or excessive sleep and altered cardiac health.