The overarching objective of this Project is to identify genetic variants and environmental factors that act, whether interactively or Independently (main effects), to influence the expression of a wide range of psychosocial, behavioral and biological characteristics [CVD and Type 2 Diabetes (T2D) endophenotypes] that increase the risk of developing CVD and T2D among healthy persons as well as increase the risk of adverse clinical events in persons in whom CVD is already manifest. To achieve this objective we shall use use three samples - PPG-1 (N=165), Caregiver (170 caregivers of a relative with Alzheimer's Disease, 170 controls) and PPG-2 (644 from 400 families);with a total N of 1000+/- - in which we have extensive data re a broad range of T2D and CVD endophenotypes to identify promising genetic variants (using both candidate genes and GWAS-derived SNPs) that are associated with these predisease endophenotypes. A major thrust of our work on this Project will be to increase our confidence in the reality of these geneendophenotype associations by replicating them, both within the three samples used by Project 1 and in the large healthy and clinical CAD samples being studied in Projects 2 and 3.
A third aim will be to work closely with Projects 2 and 3 to complete the tranlational process, by showing that the genetic variants found associated in Project 1 with T2D and CVD endophenotypes are also associated in those Projects'samples with both the prevalence and incidence of CVD and T2D and clinical course.
The knowledge gained in Project 1 and its collaboration with Projects 2 and 3 will consitute important progress toward the long range goal identifying persons at risk of developing CVD or T2D earlier in the pathogenic process, so that they, and the CVD and/or T2D endophenotype(s) accounting for their increased risk, can be targeted for interventions, to prevent the development of disease or improve prognosis.
|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|
|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|
|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|
|Haberstick, Brett C; Smolen, Andrew; Williams, Redford B et al. (2015) Population frequencies of the Triallelic 5HTTLPR in six Ethnicially diverse samples from North America, Southeast Asia, and Africa. Behav Genet 45:255-61|
|Ogle, Christin M; Rubin, David C; Siegler, Ilene C (2015) The relation between insecure attachment and posttraumatic stress: Early life versus adulthood traumas. Psychol Trauma 7:324-32|
|Ward-Caviness, Cavin K; Kraus, William E; Blach, Colette et al. (2015) Association of Roadway Proximity with Fasting Plasma Glucose and Metabolic Risk Factors for Cardiovascular Disease in a Cross-Sectional Study of Cardiac Catheterization Patients. Environ Health Perspect 123:1007-14|
|Singh, Abanish; Babyak, Michael A; Brummett, Beverly H et al. (2015) Computing a Synthetic Chronic Psychosocial Stress Measurement in Multiple Datasets and its Application in the Replication of G Ã— E Interactions of the EBF1 Gene. Genet Epidemiol 39:489-97|
|Boyle, Stephen H; Georgiades, Anastasia; Brummett, Beverly H et al. (2015) Associations between central nervous system serotonin, fasting glucose, and hostility in African American females. Ann Behav Med 49:49-57|
|Davey, Adam; Siegler, Ilene C; Martin, Peter et al. (2015) Personality Structure Among Centenarians: The Georgia Centenarian Study. Exp Aging Res 41:361-85|
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