The vast majority of pharmacogenomic studies have been conducted on exclusively European decent populations, thereby precluding the discovery and translation of African American specific genetic variation into precision medicine. This imbalance in discovery and translational science has hindered our ability to deliver precision medicine to 1 in 7 Americans. Currently several academic medical institutions are incorporating Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines into practice. Without accounting for new variants found exclusively in African Americans, clinical recommendations based solely on genetic biomarkers found in European populations could result in misclassification of drug response in African Americans. Furthermore, there are several well-established, clinically actionable pharmacogenomic associations (such as the antiplatelet agent, Clopidogrel) that completely lack discovery efforts in African Americans. Without both discovery and translational efforts in African Americans, precision medicine for all will not be a reality. A such, we formed a Transdisciplinary Collaborative Center (TCC) dubbed ACCOuNT (African American Cardiovascular pharmacogenetic Consortium) to discover novel genetic variants in African Americans related to clinically actionable cardiovascular phenotypes and to incorporating African American specific SNPs into clinical recommendations, which can be delivered to physicians at the point of care. We have partnered with academic institutions, patient organizations, and African American community leaders in both Chicago and in the District of Columbia (DC) to developed our focused effort in precision medicine. The TCC will consist of four cores (Administrative, Consortium, Implementation, and Data Analysis and Harmonization) as well as two research projects focused on discovery and translation of genetic findings. The primary aims of this proposal are: 1) Establish an African Ancestry pharmacogenomics research network to facilitate genomic research and to establish a public genomics resource for continued translational research; 2) Establish mechanisms to support implementation, diffusion, and continuing evaluation and improvement of precision medicine in African Americans; and 3) Engage community leaders in African American pharmacogenomic research. Our proposed TCC will be focused on closing this gap in precision medicine by undertaking discovery projects centering on SNP discovery in African Americans and clinical translational initiatives that will assess the impact of genetic biomarkers on clinical outcomes in African Americans in an inpatient setting. This model will establish a pipeline in which basic sciences discovery can pass quickly into clinical translational studies, which will in turn supply the needed clinical outcomes for implementation. We have incorporated patient centered approaches to each of these initiatives and have begun to work within African American communities on the design, recruitment and dissemination of this important work.

Public Health Relevance

The diverse group of experts that form ACCOuNT (African American Cardiovascular pharmacogenetic Consortium), will develop a model for the discovery, translation and implementation of precision medicine in African Americans that will lay the ground work for continued investment and growth in minority pharmacogenomics. With the involvement of institutional and community partners throughout two major American cities, Chicago and the District of Columbia, we will establish the largest repository of pharmacogenomic information on African Americans as well as lasting infrastructure that can be utilized to spur continued research in this understudied area of precision medicine.

National Institute of Health (NIH)
National Institute on Minority Health and Health Disparities (NIMHD)
Specialized Center--Cooperative Agreements (U54)
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Special Emphasis Panel (ZMD1)
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Sayre, Michael
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Northwestern University at Chicago
Schools of Medicine
United States
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De, Tanima; Alarcon, Cristina; Hernandez, Wenndy et al. (2018) Association of Genetic Variants With Warfarin-Associated Bleeding Among Patients of African Descent. JAMA 320:1670-1677
De, Tanima; Park, C Sehwan; Perera, Minoli A (2018) Cardiovascular Pharmacogenomics: Does It Matter If You're Black or White? Annu Rev Pharmacol Toxicol :