? Project 4:Clinical interventions & gene-by-stress effects on cardiometabolic endophenotypes For decades, our combined research groups (Williams, Kraus, Blumenthal, Jiang) have investigated the effects of psychological stress on cardiovascular disease, and the effects of exercise training, stress reduction and pharmacologic interventions to modify stress effects on cardiometabolic risk. Drs. Blumenthal's and Jiang's group has been a leader in intervention studies. Dr. Williams' group has been a leader in attempts to understand how genetic variation can modify these effects and potentially explain variations in the effectiveness of lifestyle interventions on cardiovascular outcomes. For example, they have described how BDNF, EBF1, DRD2, 5HTR2C each have specific gene-by-stress effects modified by other demographic characteristics that are associated with cardiometabolic phenotypes. However, these effects have been described primarily using cross-sectional associations in large datasets in studies that were not designed to investigate intervention effects on these relations. To move the field forward scientifically and to begin to develop effective clinical interventions to modify the adverse gene-by-stress interactions that we have identified, we will need to understand whether established lifestyle, behavioral and pharmacologic interventions can equally affect favorable cardiometabolic effects irrespective of these genetic effects, and conversely, whether the described gene-by-stress interactions affect the influence of established lifestyle, behavioral and pharmacologic interventions on cardiometabolic health. A number of important questions remain largely or totally unexplored in the field. 1) Do clinical interventions designed to target cardiometabolic risk modify or mollify the adverse gene-by-stress interactions being illuminated in Projects 1 and 2? 2) Do genes, chronic stress, or gene-by-stress effects predict who will adhere to favorable clinical interventions that favorably influence cardiometabolic health? 3) Can one demonstrate clinically, using targeted pharmacologic and genetic testing, that the gene-by-stress interactions that we have identified are really active and are not merely chance statistical associations? We have brought together a number of unique cohorts from completed lifestyle and intervention trials to begin to address these important scientific and clinical questions. In this Project 4, we will be studying the effects of stress-by-gene interactions on intervention effects and the converse in established cohorts from lifestyle and pharmacologic datasets; the effects of gene-by-stress interactions on adherence to exercise interventions; and the effects of gene-targeted pharmacologic agents on gene-by-stress effects on cardiometabolic phenotypes. Molecular data already collected will be provided to Project 3 to identify potential molecular pathways involved in the observed effects.
PROJECT 4 ? Gene x stress interactions? & responses to behavioral & drug interventions PUBLIC HEALTH RELEVANCE Psychosocial stress has a profound impact on cardiovascular disease and disease risk. We have been studying how psychosocial stress affects individuals differently depending upon their inherited genetic makeup. To date, little is known about how individuals with genetic risk for cardiovascular disease and/or with significant psychological stress can modify their risk through either lifestyle changes (exercise, diet, stress management) or through pharmacologic therapy. In this project, we will probe these issues and examine how psychological stress, genes that interact with stress, and clinical interventions interact to modify cardiometabolic risk.
|Singh, Abanish; Babyak, Michael A; Brummett, Beverly H et al. (2018) Developing a synthetic psychosocial stress measure and harmonizing CVD-risk data: a way forward to GxE meta- and mega-analyses. BMC Res Notes 11:504|
|Ward-Caviness, Cavin K; Kraus, William E; Blach, Colette et al. (2018) Associations Between Residential Proximity to Traffic and Vascular Disease in a Cardiac Catheterization Cohort. Arterioscler Thromb Vasc Biol 38:275-282|
|Mirowsky, Jaime E; Devlin, Robert B; Diaz-Sanchez, David et al. (2017) A novel approach for measuring residential socioeconomic factors associated with cardiovascular and metabolic health. J Expo Sci Environ Epidemiol 27:281-289|
|Williams, Redford B; Bishop, George D; Haberstick, Brett C et al. (2017) Population differences in associations of serotonin transporter promoter polymorphism (5HTTLPR) di- and triallelic genotypes with blood pressure and hypertension prevalence. Am Heart J 185:110-122|
|Jiang, Rong; Babyak, Michael A; Brummett, Beverly H et al. (2017) Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism interacts with gender to influence cortisol responses to mental stress. Psychoneuroendocrinology 79:13-19|
|Jiang, Rong; Babyak, Michael A; Brummett, Beverly H et al. (2017) Brain-derived neurotrophic factor rs6265 (Val66Met) polymorphism is associated with disease severity and incidence of cardiovascular events in a patient cohort. Am Heart J 190:40-45|
|Haberstick, Brett C; Boardman, Jason D; Wagner, Brandon et al. (2016) Depression, Stressful Life Events, and the Impact of Variation in the Serotonin Transporter: Findings from the National Longitudinal Study of Adolescent to Adult Health (Add Health). PLoS One 11:e0148373|
|Ward-Caviness, Cavin K; Neas, Lucas M; Blach, Colette et al. (2016) Genetic Variants in the Bone Morphogenic Protein Gene Family Modify the Association between Residential Exposure to Traffic and Peripheral Arterial Disease. PLoS One 11:e0152670|
|McGarrah, Robert W; Craig, Damian M; Haynes, Carol et al. (2016) High-density lipoprotein subclass measurements improve mortality risk prediction, discrimination and reclassification in a cardiac catheterization cohort. Atherosclerosis 246:229-35|
|Ogle, Christin M; Rubin, David C; Siegler, Ilene C (2016) Accounting for Posttraumatic Stress Disorder Symptom Severity With Pre- and Posttrauma Measures: A Longitudinal Study of Older Adults. Clin Psychol Sci 4:272-286|
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