African Americans and European Americans exhibit distinct gene expression patterns across tissues and tumors that are associated with immunologic and infectious functions and environmental exposures

Abstract

The COVID-19 pandemic has affected African American populations disproportionately with respect to prevalence, morbidity, and mortality. Because gene expression profiles represent combined genetic, socioenvironmental, and physiological effects, and could provide therapeutic biomarkers and environmental mitigation strategies, we undertook a large-scale assessment of differential gene expression between African Americans and European Americans. To do this, we mined RNA-Seq datasets from normal and diseased (tumor) conditions whose metadata could be used to evaluate differential patterns. We observed widespread differential expression of genes implicated in COVID-19 and integral to epithelial boundary function, inflammation, infection, and reactive oxygen stress. Notably, expression of the little-studied F8A2 gene is up to 40-fold greater in African Americans. F8A2, like F8A1, encodes HAP40 protein, which mediates early endosome movement. African American gene expression signatures reveal increased number or activity of esophageal glandular cells and lung ACE2-positive basal keratinocytes. These findings have potential to establish prognostic signatures, refine approaches to minimizing risk of severe infection, and improve precision treatment of COVID-19.

Systematic comparison of published host gene expression signatures for bacterial/viral discrimination

“…We observed performance differences due to race and ethnicity that were consistent with ancestry-based variation in the immune response [47,48]. However, they could also be due to other confounding variables including dataset-specific factors, such as clinical adjudication accuracy.…”

Trends in social exposure to SARS-Cov-2 in France. Evidence from the national socio-epidemiological cohort – EPICOV

“…The copyright holder for this preprint this version posted October 26, 2021. ; https://doi.org/10.1101/2021.10.25.21265456 doi: medRxiv preprint hypothesized, (15) , (16,17) but without evidence. (18) Inequalities in mortality could be primarily driven by differences in exposure to infection.…”

“…African Americans, Hispanics, and other ethnic minority groups were disproportionately affected by SARS-CoV-2, as mostly documented during the first epidemic wave in terms of diagnosed infection, hospitalization,( 6) , (8) and mortality. (7) , (8) Among potential reasons for higher incidence or severity related to ethnicity, biological susceptibilities have been hypothesized, (15) , (16,17) but without evidence. (18) Inequalities in mortality could be primarily driven by differences in exposure to infection.…”