GENETICS, HOSTILITY & BIOLOGY OF STRESS IN DAILY LIFE

遗传学、敌意

• 批准号: 6831884
• 负责人: James D. Lane
• 金额: $ 15.38万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-12-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6831884
• 关键词: African American; angers; behavioral /social science research tag; behavioral genetics; blood pressure; cardiovascular disorder risk; caucasian American; clinical research; gene environment interaction; gene expression; heart rate; human subject; lifestyle; stress

The goal of the Program Project is to identify genetic variations that interact with the environment to affect the expression and clustering of psychosocial and biobehavioral endophenotypes that increase cardiovascular disease (CVD). Exaggerated stress reactivity is likely to be an important CVD endophenotype. Evidence suggests that exaggerated reactivity is associated with increased CVD, and evidence suggests it has a genetic basis. Ambulatory measures of reactivity provide a crucial complement to laboratory studies because they demonstrate the ecological validity of the relationship of hostility and exaggerated reactivity in the environment where pathogenesis occurs. Project 3 will provide measurements of ambulatory stress reactivity for each of a sample of 400 probands (half African American and half Caucasian, half men and half women, and half scoring in the top and half in the bottom 20% on a valid, measure of hostility that predicts CVD and has heritability estimates of 40-55%) and at least one sibling for every proband, to make a total sample of 800-1200 subjects who will participate in the protocol of this project. These measurements will include blood pressure and heart rate variability, catecholamine and cortisol reactivity, and subjective stress and negative mood collected during a 24-hour period of normal daily activities in the natural environment. Both total variability and variability directly attributable to perceived stress and to negative mood will be available for cardiovascular measures, through the use of novel techniques of regression analysis. Neurohumoral activity will be determined by assay of urinary levels in daytime and overnight samples. Personal digital assistants (PDAs) will be used to collect subjective ratings during ambulatory monitoring. Our first goal will be to evaluate a minimum of 41 candidate genes/loci that act directly, in interaction with environmental factors, as a function of linkage disequilibrium with other sites, or membership in haplotypes, to influence hostility and ambulatory cardiovascular & neuroendocrine function. Collected ambulatory data will be combined with data from other Projects to determine genes/loci that affect the clustering of exaggerated ambulatory stress reactivity with hostility and other psychosocial and biobehavioral endophenotypes for CVD. In collaboration with the other Projects, Project 3 will advance our understanding of the genetic influences and gene/environment interactions that account for one of the most important CVD risk factors, hostility. The Projects will also explore how SES, sex and ethnicity may moderate the expression of involved genes. Program Project research activities will provide a comprehensive view of the clustering of CVD risk factors across multiple psychosocial and biobehavioral domains, which should lead to a clear understanding of the determinants of CVD and their genetic basis.

该计划项目的目标是确定与环境相互作用的基因变异，以影响增加心血管疾病(CVD)的心理社会和生物行为内表型的表达和聚集。过度的应激反应可能是CVD的一种重要的内表型。有证据表明，过度的反应性与心血管疾病的增加有关，而且有证据表明，这是有遗传基础的。动态的反应性测量为实验室研究提供了一个重要的补充，因为它们证明了在发生发病的环境中敌意和夸大的反应性之间关系的生态有效性。项目3将为400名先证者(一半是非洲裔美国人，一半是高加索人，一半是男性，一半是女性，一半是得分最高的，一半是得分最低的20%)和至少一个兄弟姐妹中的每一个提供动态应激反应性的测量，这种测量可以预测心血管疾病，遗传力估计为40%-55%。 每名先证者，共抽取800-1200名将参与本项目方案的受试者作为样本。这些测量将包括血压和心率变异性、儿茶酚胺和皮质醇反应性，以及在自然环境中24小时正常日常活动期间收集的主观压力和负面情绪。通过使用新的回归分析技术，心血管测量将可使用总变异性和直接可归因于感知到的压力和负面情绪的变异性。神经体液活性将通过分析白天和过夜样本的尿液水平来确定。在动态监测期间，将使用个人数字助理(PDA)收集主观评分。我们的第一个目标是评估至少41个候选基因/基因座，这些基因/基因座与环境因素相互作用，作为与其他位点的连锁不平衡的函数，或作为单倍型的成员，影响敌意和动态心血管& 神经内分泌功能。收集的动态数据将与其他项目的数据相结合，以确定影响心血管疾病的夸大动态应激反应和敌意以及其他心理社会和生物行为内表型聚集的基因/位点。在与其他项目的合作中，项目3将促进我们对基因影响和基因/环境相互作用的理解，这些因素是最重要的 心血管疾病的危险因素，敌意。这些项目还将探索社会经济地位、性别和种族如何调节相关基因的表达。方案项目研究活动将全面了解心血管疾病风险因素在多个心理社会和生物行为领域的聚集情况，这将导致对心血管疾病的决定因素及其遗传基础有一个清楚的了解。