Perceived everyday discrimination and leukocyte gene expression in a nationally representative sample of U.S. Adults

Perceived everyday discrimination is a psychosocial stressor that is adversely associated with biological health. These associations may be partly mediated by the modulation of leukocyte gene expression through stress-related neuroendocrine pathways. The Conserved Transcriptional Response to Adversity (CTRA) provides a framework for examining how everyday discrimination may alter molecular signaling pathways through coordinated changes in gene expression. This study quantified associations between perceived everyday discrimination and CTRA patterns in a diverse, nationally representative sample of U.S. adults. Data were drawn from Wave 5 (2016-2017) of the National Longitudinal Study of Adolescent to Adult Health (Add Health). Perceived everyday discrimination was assessed using the validated Everyday Discrimination Scale and standardized using z-scores. CTRA gene expression was evaluated using an a priori-defined set of 52 genes. Weighted regression models tested associations between everyday discrimination and CTRA, sequentially adjusting for sociodemographic, behavioral, clinical, and technical covariates. We found no evidence of a linear association between discrimination and CTRA. However, exploratory analyses suggested a non-linear (inverted-U) relationship (b = -0.023, 95% CI: -0.044, -0.001, p = 0.036); the association was directionally positive at lower exposure but reached significance only at the highest levels, where CTRA expression declined as discrimination increased.. This pattern indicates that the relationships of discrimination with gene expression may not follow a straightforward dose-response pattern, instead reaching a threshold beyond which additional exposure elicits reduced biological reactivity, possibly reflecting adaptation or coping among those exposed to chronic discrimination.