Genetic and Environment Influences on Expression of CVD Endophenotypes

遗传和环境对CVD内表型表达的影响

• 批准号: 8378676
• 负责人: Redford B WILLIAMS
• 金额: $ 39.11万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8378676
• 关键词: Accounting; Acute; Adrenergic Receptor; Affect; Alcohol consumption; Alleles; Alzheimer' s Disease; Behavioral; Biologic Characteristic; Biological Factors; Brain; Candidate Disease Gene; Cardiovascular Diseases; Cardiovascular Physiology; Caregivers; Chronic stress; Clinical; Collaborations; Complex; Data; Development; Disease; Documentation; Environment; Environmental Risk Factor; Event; Exposure to; Failure; Family; Funding; Genes; Genetic; Genetic Variation; Genotype; Goals; Health behavior; Hemostatic Agents; Hostility; Hyperphagia; Hypertension; Incidence; Inflammatory; Intervention; Knowledge; Mental Depression; Metabolic; Metabolic syndrome; Modeling; National Human Genome Research Institute; Neurosecretory Systems; Neurotransmitters; Non-Insulin-Dependent Diabetes Mellitus; Pathogenesis; Pathway interactions; Persons; Phenotype; Population; Postdoctoral Fellow; Precipitation; Prevalence; Process; Progress Reports; Psyche structure; Psychosocial Factor; Relative (related person); Research; Risk; Risk Factors; SNP genotyping; Sampling; Severities; Smoking; Social support; Stress; System; Testing; Time; Variant; Work; biobehavior; cardiovascular disorder risk; depressive symptoms; endophenotype; environmental stressor; genetic variant; genome wide association study; improved; monoamine; outcome forecast; prevent; programs; psychologic; psychosocial; sex; stem; success; trait; working group

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 geneendo phenotype 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.

该项目的总体目的是确定行动的遗传变异和环境因素，无论是互动或独立的（主要影响），以影响广泛的心理社会，行为和生物学特征[CVD和2型糖尿病（T2D）内型型]的表达，从而增加了在健康中的临床风险，并增加了健康的人的风险，以及对健康的人的影响，以及cvd和T2D的风险，以及cvd和T2D的风险增加，而这些人的风险又增加了，并且构成了cvd和T2D的风险。 显现。为了实现这一目标，我们将使用三个样本-PPG-1（n = 165），护理人员（170个患有阿尔茨海默氏病的亲戚的护理人员，170个对照）和PPG-2（400个家庭的644个）；在总共1000 +/-的情况下，我们拥有广泛的数据，可以识别出与这些易患性疾病的内聚型相关的有希望的遗传变异（使用候选基因和GWAS衍生的SNP）。我们在该项目上工作的主要作用将是，通过复制这些基因多表型关联的现实信心，通过在项目1使用的三个样本中以及在项目2和3中研究的大型健康和临床的CAD样本中，这两个样本都将与项目2和3密切相关的项目，以在项目2和3中进行研究。在这些项目样本中，内型型也与CVD和T2D和临床过程的发生率和发病率相关联。