African American Cardiovascular Pharmacogenetic CONsorTium (ACCOuNT): Discovery & Translation 

PI: David Meltzer, Department of Medicine (Hospital Medicine)

Dates: 08/19/2016 – 05/31/2021
Funder: NIH

Description: Pharmacogenomics is aimed at identifying genetic variation (SNPs) that influence inter-individual differences in drug response and adverse events and has widespread clinical relevance. Its application promises to enable targeted drug administration, improve therapeutic outcome, and inform drug development. Pharmacogenomic insights have improved our understanding of the underlying pathways and mechanisms behind adverse drug reactions, which account for approximately 100,000 deaths per year in the US and markedly increase healthcare costs. The vast majority of pharmacogenomic association studies, which are the drivers of discovery in the field of precision medicine, have been conducted on exclusively European populations, thereby precluding the discovery of African American specific genetic biomarkers that affect drug phenotypes. Without scientific inquiry on the presence and association of these SNPs to drug response, our ability to deliver precision medicine to 1 in 7 Americans is severely hampered. To close this growing heath disparity in African American precision medicine we formed ACCOuNT and are proposing a discovery project within cardiovascular pharmacogenomics. In our Discovery project, we hypothesize that through discovery efforts centered on African Americans, we will identify predictive biomarkers of cardiovascular drug response and disease susceptibility that can be investigated in translational outcome studies. We will test this hypothesis with the following aims: 1) Determine genetic predictors of drug response to thrombotic therapy using genome-wide association methodology, 2) Investigate the role of gene expression/splice variants and eQTLs on drug response phenotypes for elucidation of biological mechanisms and genetic regulation of these phenotypes, and 3) Create a publically available and searchable database to house the results of the genomic and transcriptomic studies in African Americans. Through the infrastructure of ACCOuNT we will conduct our discovery efforts with a patient-centered approach that incorporates the input of community partners, frontline physicians and African American patients. We anticipate that these studies will reveal novel SNP associations and gene regulation pathways. Several potential research areas/questions may develop from this work. Our proposed genomics database will serve as needed resource within the pharmacogenomics scientific community, which currently lacks comprehensive genomics and transcriptomic information on African Americans. These new research avenues have the potential of feeding seamlessly into our translational project and pilot projects thus allowing us to leverage our Transdisciplinary Collaborative Center to move implementation of precision medicine in African Americans faster than previous efforts.