In the lab of Dr. Alexis Battle, we analyzed genetic data from over 400,000 individuals and discovered a new area of the genome that is associated with the development of clinical heart failure. We then confirmed that finding in an independent cohort of over a million participants.
The novel DNA region had a previously unknown function, so we employed several computational algorithms to combine a series of other genetic data (gene expression, epigenetic regulation and 3D-DNA folding information) and predicted that the novel region affects the expression of a nearby structural gene, known as ACTN2. We then confirmed that prediction with direct genome editing, using CRISPR/Cas9 in differentiated cardiomyocytes. The discovery is important, as it increases our understanding of heart failure pathogenesis and could, in the future, be used to identify people at risk or to develop novel therapies for the disease.