Considerations for Cardiovascular Genetic and Genomic Research With Marginalized Racial and Ethnic Groups and Indigenous Peoples: A Scientific Statement From the American Heart Association

Abstract

Historically marginalized racial and ethnic groups and Indigenous peoples are burdened by significant health inequities that are compounded by their underrepresentation in genetic and genomic research. Of all genome-wide association study participants, ≈79% are of European descent, despite this group constituting only 16% of the global population. For underrepresented populations, polygenic risk scores derived from these studies are less accurate in predicting disease phenotypes, novel population-specific genetic variations may be misclassified as potentially pathogenic, and there is a lack of understanding of how different populations metabolize drugs. Although inclusion of marginalized racial and ethnic groups and Indigenous peoples in genetic and genomic research is crucial, scientific studies must be guided by ethical principles of respect, honesty, justice, reciprocity, and care for individuals and communities. Special considerations are needed to support research that benefits the scientific community as well as Indigenous peoples and marginalized groups. Before a project begins, collaboration with community leaders and agencies can lead to successful implementation of the study. Throughout the study, consideration must be given to issues such as implications of informed consent for individuals and communities, dissemination of findings through scientific and community avenues, and implications of community identity for data governance and sharing. Attention to these issues is critical, given historical harms in biomedical research that marginalized groups and Indigenous peoples have suffered. Conducting genetic and genomic research in partnership with Indigenous peoples and marginalized groups guided by ethical principles provides a pathway for scientific advances that will enhance prevention and treatment of cardiovascular disease for everyone.

Corin Missense Variants, Blood Pressure, and Hypertension in 11 322 Black Individuals: Insights From REGARDS and the Jackson Heart Study

“… 58 This study underlines the need for a more comprehensive approach cognizant of the multiple pathways when evaluating complex cardiovascular traits and a greater representation of minority populations in genetic studies. 40 , 45 , 58 Our work also underscores the importance of adequate replication of genetic associations in multiple, diverse population‐based cohorts. 40 , 45 Further evaluation of these Corin missense variants in a younger, disease‐free population with longitudinal data on BP and circulating NP levels may provide a definitive understanding of the impact of the variants on BP traits.…”

“… 40 , 45 , 58 Our work also underscores the importance of adequate replication of genetic associations in multiple, diverse population‐based cohorts. 40 , 45 Further evaluation of these Corin missense variants in a younger, disease‐free population with longitudinal data on BP and circulating NP levels may provide a definitive understanding of the impact of the variants on BP traits.…”

“…GWAS investigations in underrepresented ethnic groups may help us better understand the genome‐wide impact of the Corin locus on circulating NP levels and BP. 40 , 45 Additionally, the impact of epigenetic changes that differ based on the geographic and temporal distribution of the study population may also impact the influence of the Corin variants on the complex and tightly regulated phenotype of BP at an individual level. 46 , 47 , 48 Previously, the impact of these Corin variants on the left ventricular mass has been shown to be more predominant at higher BP values.…”

Sex-dimorphic gene effects on survival outcomes in people with coronary artery disease

“…The burden of CAD-related mortality falls heavily on Black and Brown people, particularly women [ 6 , 8 , 68 ]. Yet their limited representation in genomics research continues to deny them potential benefits of such research [ 69 , 70 ]. Furthermore, it diminishes our ability to study whether and how population genomic effects interact with social determinants of health and discrimination as contributors to disparities in mortality [ 71 , 72 ].…”

Current state and future directions of genomic medicine in aortic dissection: A path to prevention and personalized care

“…The American Heart Association issued a scientific statement in 2021 on genomic research in marginalized populations that underscored the importance of equitable research design for effective translation to clinical care [ 48 ]. Special consideration should be given to community collaboration, transparency, and improving trust between researchers and marginalized populations.…”