Genetic and Environment Influences on Expression of CVD Endophenotypes

该项目的总体目标是确定遗传变异和环境因素，无论是相互作用还是独立作用（主要影响），影响广泛的社会心理、行为和生物学特征（CVD和2型糖尿病（T2D）内表型）的表达，这些特征增加了健康人患CVD和T2D的风险，也增加了CVD患者出现不良临床事件的风险。为了实现这一目标，我们将使用三个样本- PPG-1 (N=165)，照顾者（170名患有阿尔茨海默病的亲属的照顾者，170名对照组）和PPG-2（来自400个家庭的644名）；总N为1000+/-，其中我们有广泛的T2D和CVD内表型数据，以确定与这些疾病前内表型相关的有希望的遗传变异（使用候选基因和gwas衍生的snp）。我们在这个项目上的主要工作将是通过在项目1使用的三个样本以及项目2和3研究的大型健康和临床CAD样本中复制这些基因表型关联来增加我们对这些基因表型关联的真实性的信心。第三个目标是与项目2和项目3密切合作，通过证明项目1中发现的与T2D和CVD内表型相关的遗传变异在这些项目的样本中也与CVD和T2D的患病率和发病率以及临床病程相关，来完成转化过程。

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.