Am I ATTRisk? Health empowerment through population genomic screening for transthyretin amyloidosis

About This Grant

PROJECT SUMMARY Tremendous potential to improve cardiovascular outcomes can be realized by tackling an important disease that disproportionately afflicts African American (AA) and Hispanic/Latino (H/L) individuals: hereditary (variant) transthyretin amyloidosis (ATTRv). Caused by mutations in the TTR gene, ATTRv leads to chronic heart failure and neuropathy, contributing to poorer outcomes in these populations. The commonest TTR mutation, V142I, is found in 4% of AA and 1% of H/L individuals (~2 million Americans), however, because genetic testing is vastly underutilized, 97% of carriers do not know they have it. Since ATTRv is a treatable condition when therapies are started promptly, it is imperative for carriers to learn their genetic status so they can be monitored for signs and symptoms. Population-based genomic screening is an innovative and cost-effective preventive health strategy that can be leveraged to improve V142I detection. Such an approach is already underway to effectively screen for cancer risk and promote early detection in certain high risk groups (i.e. in Ashkenazi Jews, where the BRCA1/2 mutation rate is 2.5%, lower than that of V142I). Applying a population-based genomic screening effort toward a condition that mainly impacts AA and H/L individuals requires special attention to ensure adequate access to genetics specialists, use of culturally sensitive communication strategies, understanding preconceived attitudes around genetic testing and other potential barriers. In Aim 1 of this study, we will partner with secular and faith-based organizations in NYC to conduct focus groups with AA and H/L community members and use implementation mapping to perform a needs assessment for acceptability and feasibility of TTR genomic screening. This process will enable us to develop a set of effective strategies to communicate ATTRv risk information in these communities. In Aim 2 of the study, we will incorporate the expertise of our multidisciplinary team (community engagement, implementation science, health/science communication, genetic counseling) and strategic outcomes from Aim 1 to customize a digital TTR genomic screening tool and test its implementation in 1,100 AA and H/L community participants. The primary objective will be to determine the efficacy of TTR genomic screening in populations that are most at risk and better understand attitudes, behaviors, barriers and facilitators to this novel program. If successful, we anticipate that this strategy can be implemented across the US to empower millions of individuals to know their risk and promote early detection and more effective treatment for ATTRv.