A Bioecological Approach to Understanding the Interaction of Environmental Stress and Genetic Susceptibility in Influencing Cortisol and Blood Pressure in African American Adults

African Americans are disproportionately affected by high blood pressure, a precursor to cardiovascular disease. Bioecological, biomedical, and gene-environment interaction theories were integrated to test the impact of environmental stress and genetic susceptibility on stress-related outcomes, including waking cortisol, perceived stress, and blood pressure in African-American adults. The primary aim of the study was to investigate the effects of neighborhood socioeconomic status (SES), neighborhood satisfaction, and neighborhood collective efficacy on waking cortisol, perceived stress, and blood pressure and to determine whether genetic risk for increased glucocorticoid receptor sensitivity moderated those relations in a gene-by-environment (GxE) interaction. A secondary aim was to investigate a potential mechanistic model whereby cortisol and perceived stress were expected to mediate the influence of neighborhood factors on BP, and also expected to interact with genetic risk to influence BP in a moderated mediation design. Blood pressure, saliva cortisol, buccal swab gene samples, psychosocial surveys, and geographic census data were collected from 450 African American adult participants. Three glucocorticoid receptor polymorphisms (Bcl1, FHBP5, and 9β) that have been linked to cortisol and blood pressure outcomes were genotyped and indexed into a single genetic risk factor. Aims were tested statistically using path analysis for estimating interaction effects, and for testing moderated mediation effects using the product of coefficients method with bootstrapped confidence intervals. The sample was 70% female and results of the primary and secondary models indicated that neighborhood SES was negatively related to waking cortisol and that waking cortisol was negatively related to systolic blood pressure. Follow-up analyses revealed a significant GxE interaction predicting perceived stress, and a trend for predicting afternoon cortisol, and systolic blood pressure. The pattern was consistent across the interaction models and indicated that individuals with high genetic risk had poorer outcomes in poorer environments and better outcomes in better environments; individuals with low genetic risk showed almost no environmental interaction. The pattern was consistent with a differential susceptibility/plasticity GxE effect, in contrast to more traditional dual risk or diathesis-stress effects. These findings are the first to assess gene-by-neighborhood interactions in African-American adults, as they impact cortisol and BP, and they may contribute to a comprehensive and contextually relevant understanding of high BP and cardiovascular health disparity. Conclusions may inform the development of innovative, targeted prevention efforts, and public policy efforts to decrease BP health disparity through greater consideration of neighborhood factors, and differential susceptibility to both more and less positive environments