Grant: Operating Grant

The aortic valve is a key component of the heart that ensures proper circulation of blood. Calcification of the aortic valve, or more specifically aortic stenosis, is the third leading cause of heart disease in adults. The incidence increases with age and with the current shift toward an older population, it is likely to become a major societal and economic burden. There is currently no medical treatment available other than open heart surgery to replace the diseased native valve by a prosthetic heart valve. It is thus urgent to understand the cause of the disease at the most fundamental levels in order to elucidate new therapeutic options. Many factors are predicted to cause the disease and an important genetic predisposition is anticipated. However, only a small number of studies have tried to identify the susceptibility genes. In this research program, we plan to expand this work using a new genomic approach called genome-wide association (GWA) study. This approach is the gold standard to identify susceptibility genes in human diseases. To achieve the first GWA study on aortic stenosis, we propose to recruit a cohort of control individuals to match an existing cohort of patients with the disease that we have collected during the last few years. This strategy will allow us to build a case-control series of patients with aortic stenosis (750 cases and 750 controls) and to perform the most effective genetic analyses. In addition, the creation of this large case-control cohort will serve as a major research resource to study the genetics of aortic stenosis for many years to come. The ultimate goal is to develop a comprehensive research program on the genetics of aortic stenosis in order to elucidate its genetic determinants. Overall, identifying causal and susceptibility genes will increase our understanding of the disease process, which can subsequently lead to innovative therapeutic strategies to treat this life-threatening and frequent disease.