Genome-wide transcriptome differences associated with perceived discrimination in an urban, community-dwelling middle-aged cohort
Discrimination is a type of social adversity defined as unfair treatment and prejudice against individuals due to membership of a specific group. Discrimination has been linked to several age-related outcomes such as cognitive decline, inflammation, and cardiovascular disease. However, the molecular drivers to these observations are poorly understood. Social adverse factors have been associated with proinflammatory and interferon gene expression, a phenomenon described as Conserved Transcriptome Response to Adversity. It is not known whether there are additional genes whose transcription is associated with exposure to discrimination among both African American and White adults.  In this study, we have examined how perceived discrimination in African American and White adults affects genome-wide transcriptome differences using RNA sequencing. Perceived discrimination was measured based on responses to lifetime discrimination and racial discrimination questionnaires. Differential gene expression and pathway analysis was conducted in a cohort (N=59) stratified by race, sex, and discrimination exposure. We found that there were 28 significantly differentially expressed genes associated with high discrimination exposure in African American adults when compared to White adults with high discrimination exposure. The most significantly upregulated genes among African Americans with high discrimination exposure were related to immune function  immunoglobulin lambda variable 2-11 (IGLV2-11), S100 calcium binding protein B (S100B), immunoglobulin kappa variable 3-20 (IGKV3-20), immunoglobulin kappa variable 4-1 (IGKV4-1); the most significantly downregulated genes were associated with immune modulation and cancer, lung cancer associated transcript 1 (LUCAT1), thrombospondin 1 (THBS1), and actin related protein 2/3 complex inhibitor (ARPIN).  In addition, the most significantly upregulated Gene Ontology (GO) biological process among African American men with high exposure to discrimination compared to White male adults with high exposure to discrimination was regulation of cytokine biosynthetic processes. Conversely, immune response was the most significantly downregulated GO biological process among African American women with high discrimination exposure compared White women with high discrimination exposure. Understanding the biological pathways through which adverse social factors like discrimination affect gene expression will be critical in advancing knowledge of age-related health disparities. Overall design: In this study, we have examined how perceived discrimination in African American and White adults affects genome-wide transcriptome differences using RNA sequencing. Peripheral blood mononuclear cells (PBMCs) were isolated from HANDLS participants that were exposed to either low or high perceived discrimination. Total RNA was isolated from PBMCs and RNA sequencing was performed.