Sudden unexpected death (SUD) is a tragic event, with profound implications for the family and community when it occurs in young people (age 1 - 40 years). Because inherited cardiac disease is an important cause of SUD in young people, surviving family members may be at risk for sudden death. A population-based estimate of inherited cardiac disease prevalence among first-degree relatives is unavailable.Cardiac channelopathies and cardiomyopathies caused by pathologic genetic variants account for approximately 30% of SUD events in the young. From a public health standpoint, it is important to understand the frequency that diseases of cardiac rhythm and function are present in surviving first-degree relatives. Intervention can change the natural history of many of these diseases and decrease further sudden death. We have experience studying families after SUD events, focusing on genetic testing of SUD probands (often called 'molecular autopsy'), but our current research does not perform any direct phenotype testing on first-degree relatives. In this AHA proposal, we will expand on prior efforts by going to the homes and communities of first-degree relatives of a SUD proband to obtain phenotype testing with an electrocardiogram and genotype testing with a non-invasive DNA collection kit.The project has three specific aims: 1) To improve our estimate of disease prevalence in first-degree relatives of a SUD proband; 2) To determine the feasibility and yield of community-based DNA extraction in children; and 3) To determine the frequency of transmitted vs. de novo potentially pathogenic variants in SUD. Our close partnership with a large medical examiner's office and our focus on in-home testing to improve the population estimate of disease are innovative ways to approach this problem. The proposed research is significant because the data will improve the evaluation and management of first-degree relatives of SUD victims. Targeting treatment to those relatives at highest risk for events should decrease further sudden death in the population. This project will advance the candidate's overall training goal, which is to become an independent researcher, with expertise in the genetic diseases that impact SUD. This grant supplements the candidate's background in clinical research and genetics by providing an opportunity for training in population science.
|Program type||Mentored Clinical & Population Research Program|
|Effective start/end date||07/01/2017 → 06/30/2019|