Stress, Gene-Environment Interaction and Cardiovascular Disease

a MiCDA Research Project Description

Investigators: Belinda L. Needham, Sharon L. R. Kardia, Bhramar Mukherjee, Jennifer A. Smith

Funding: National Heart, Lung, And Blood Institute, 2010-2016 (1 R01 HL 101161 01)

Although psychosocial stress has been hypothesized to play a role in the etiology of cardiovascular disease (CVD), empirical verifications of the effects of stress or the biological mechanisms through which stress operates remain rare. A major limitation has been the absence of population studies with direct biologic measures of stress (such as measures of levels of stress hormones), which would allow exploration of social and biological precursors to CVD. It has also become increasingly apparent that social conditions and stressors must interact with genetic makeup, and that some of these exposures may modify gene expression through changes in DNA methylation, but again, few population studies have comprehensively investigated the gene-environment interactions and epigenetic changes related to psychosocial factors.

Using data from the Multiethnic Study of Atherosclerosis, a large multiethnic population sample, we are investigating the long-term associations of the stress response (as characterized by multiple measures of stress hormones) with social/psychosocial antecedents and cardiovascular-related outcomes, as well as modifications of the stress response by variations in selected candidate genes, and links between psychosocial factors and epigenetic changes. Specifically, we are examining (1) associations of repeat measures of stress hormones with social and psychosocial factors and with biological precursors of CVD, including inflammation/hemostasis and measures of insulin resistance and adiposity; (2) interactions between cortisol levels and polymorphisms of the glucocorticoid receptor gene with respect to cardiovascular-related outcomes; (3) the extent to which polymorphisms of biologically relevant genes modify the response to a psychological stress challenge; and (4) epigenetic changes (DNA methylation) of the glucocorticoid receptor gene as well as genomic DNA methylation and their association with (a) life course social exposures; (b) cortisol and hemodynamic responses to a stress challenge; and (c) biological parameters previously linked to stress exposures.

Our study will enhance understanding not only of the epidemiologic links between stress and CVD but also of the biologic mechanisms through which these effects may be mediated. This knowledge is necessary to better understand the importance of stress and to develop salient preventive interventions.

Research Signature Theme:

Aging, Genetics, and Social Science