Genetic and Environment Effects on CVD Endophenotypes in Add Health

该项目的总体目标是确定基因变异和环境因素，无论是交互作用还是独立作用(主效应)，影响一系列心理社会、行为和生物学特征[心血管疾病和2型糖尿病(T2D)内表型]的表达，这些特征增加了健康人患心血管疾病和2型糖尿病的风险，并增加了已有心血管疾病患者发生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)，Caregiver(170名阿尔茨海默病亲属的照顾者，170名对照)和PPG-2(来自400个家庭的644人)；在这些样本中，我们拥有广泛的数据和广泛的T2D和CVD内表型，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SNPs)。我们在这个项目上工作的一个主要目的将是通过在项目1使用的三个样本以及项目2和项目3正在研究的健康和临床CAD的大样本中复制它们来增加我们对这些基因内表型相关性的真实性的信心。第三个目标将是与项目2和项目3密切合作以完成转换过程，通过表明在项目1中发现的与T2D和CVD内表型相关的基因变异也与这些项目的样本中的心血管疾病和T2D的患病率和发病率以及临床病程相关。

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.