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.
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|Brummett, Beverly H; Babyak, Michael A; Kuhn, Cynthia M et al. (2014) A functional polymorphism in the HTR2C gene associated with stress responses: a validation study. Biol Psychol 103:317-21|
|Ogle, Christin M; Rubin, David C; Siegler, Ilene C (2014) Changes in neuroticism following trauma exposure. J Pers 82:93-102|
|Siegler, Ilene C; Brummett, Beverly H; Martin, Peter et al. (2013) Consistency and timing of marital transitions and survival during midlife: the role of personality and health risk behaviors. Ann Behav Med 45:338-47|
|Berger, Jeffrey S; Becker, Richard C; Kuhn, Cynthia et al. (2013) Hyperreactive platelet phenotypes: relationship to altered serotonin transporter number, transport kinetics and intrinsic response to adrenergic co-stimulation. Thromb Haemost 109:85-92|
|Jiang, Rong; Brummett, Beverly H; Babyak, Michael A et al. (2013) Brain-derived neurotrophic factor (BDNF) Val66Met and adulthood chronic stress interact to affect depressive symptoms. J Psychiatr Res 47:233-9|
|Jiang, Rong; Brummett, Beverly H; Hauser, Elizabeth R et al. (2013) Chronic family stress moderates the association between a TOMM40 variant and triglyceride levels in two independent Caucasian samples. Biol Psychol 93:184-9|
|Ogle, Christin M; Rubin, David C; Siegler, Ilene C (2013) The impact of the developmental timing of trauma exposure on PTSD symptoms and psychosocial functioning among older adults. Dev Psychol 49:2191-200|
|Brummett, Beverly H; Babyak, Michael A; Singh, Abanish et al. (2013) Socioeconomic indices as independent correlates of C-reactive protein in the National Longitudinal Study of Adolescent Health. Psychosom Med 75:882-93|
|Nolan, Daniel; Kraus, William E; Hauser, Elizabeth et al. (2013) Genome-wide linkage analysis of cardiovascular disease biomarkers in a large, multigenerational family. PLoS One 8:e71779|
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