How Community Connection, Homophobia, and Racism Shape Gene Expression in Sexual Minority Men With and Without HIV

Objective: Although sexual minority men experience substantial discrimination, in addition to increased risk for several serious mental and somatic health problems, the biological mechanisms underlying these effects are unclear. To address this issue, we examined how experiences of social safety (i.e., community connection) and social threat (i.e., discrimination, in the forms of homophobia and racism) were related to conserved transcriptional response to adversity (CTRA) gene expression profiles across time, and whether these associations differed across HIV status, in a well-characterized, racially diverse sample of sexual minority men (Mage = 22.61, SD = 1.90). Method: Experiences of community connection, homophobia, and racism were assessed via self-report, and blood samples were obtained at three timepoints over approximately 2 years. We then used these blood samples to characterize participants' CTRA gene expression, which we quantified using an a priori 53-transcript composite score derived from RNA sequencing data from peripheral blood leukocytes. Results: As hypothesized, greater community connection was significantly related to decreased CTRA gene expression across time. These effects were similar regardless of HIV status and were robust to statistical adjustment for several potential confounding factors. In contrast, neither homophobia nor racism were related to CTRA gene expression. Conclusion: These results suggest that community connection may be a protective factor that reduces biological processes known to negatively impact health. Consequently, interventions and policies aimed at reducing health disparities in marginalized populations may benefit from increasing community connection and inclusion.