Resolving the genetic architecture of complex cardiovascular disease through phenotype refinement.

The overarching goal of this project is to improve care for patients with cardiovascular disease (CVD), including common diseases such as heart failure, atrial fibrillation, coronary artery disease, and peripheral artery disease. CVD is a leading cause of death globally, and it is associated with significant physical limitation and cost. Advances in management have improved outcomes somewhat over time, but the negative impacts of CVD continue to be high. Moreover, the pace of discovery for new treatment options has overall been sluggish. Among patients with CVD there are substantial differences in illness severity, disease progression, and response to treatment. These observations highlight the diversity among patients with CVD and suggest that there may be subgroups of patients with distinct disease causes of CVD, both environmental and genetic, that result in these differences. However, the underlying basis of these differences is incomplete. That is, we don’t fully understand why some people develop CVD and others don’t, why some people with CVD are more severely affected than others, and why some people respond more favourably to medical treatment. This project is attempting to identify distinct subsets of CVD patients with distinct features and understand their environmental, medical, and genetic causes.