Curvilinear associations of discrimination attributions with inflammatory and antiviral gene expression

Discrimination is a social determinant of health associated with adverse health outcomes through biological mechanisms such as the Conserved Transcriptional Response to Adversity (CTRA). The biological impacts of discrimination are well-documented, but the role of attributions (i.e., individuals' beliefs about why they experienced discrimination) remains unexplored. This study examined the associations of discrimination attributions with inflammatory and antiviral gene expression in a national sample of U.S. adults.

We analyzed data from 1183 participants in the Midlife in the United States study. Discrimination attributions were measured by summing the number of different attributed reasons (range: 0-13). Gene expression was assessed using a validated 51-gene CTRA panel comprising 19 pro-inflammatory and 32 interferon/antibody genes. Multivariable regression models tested linear and quadratic associations, adjusting for assay plate, leukocyte subsets, daily discrimination, demographics, socioeconomic status, and lifestyle factors.

We found no evidence of a linear association between discrimination attributions and the overall CTRA composite score. However, exploratory analyses suggested curvilinear associations between discrimination attributions and CTRA inflammatory and interferon/antibody sub-components. Expression levels were moderately elevated among those reporting no specific attributions relative to the low point observed at 2-4 attributions, and markedly elevated among those attributing discrimination to 11 or more reasons, particularly for the interferon/antibody sub-component.

Discrimination attributions relate to inflammatory and antiviral gene expression in a complex, nonlinear way. Findings suggest cognitive appraisals of discriminatory experiences may be an important factor influencing discrimination's biological impacts.