Genetic and Environmental Effects on Clinical Cardiovascular Events in a Large Co

该项目的总体目标是确定与心血管事件或冠心病(CAD)相关的遗传变异，这些变异既是主要影响，也是通过与环境应激源暴露的相互作用而产生的。为了实现这一目标，我们将评估在项目1和2中发现的与心血管疾病内表型相关的基因，或者在项目3中发现的与高血压或II型糖尿病(T2D)相关的基因，在CATHGEN样本中评估与心血管事件和血管造影记录的CAD的相关性，这些样本包括自2001年以来在杜克大学接受心导管手术的大约10,000名患者。CATHGEN是在心导管置入术时收集的独特生物样本来源，结合了经过仔细评判的临床数据库，其中包括冠状动脉疾病的血管造影术定义的范围和解剖分布、关于冠心病风险因素的广泛临床数据以及用于评估心血管事件的年度随访。CATHGEN的研究人员将在他们的NHLBI拨款的非重叠支持下，评估一系列在生物学上可能导致CHD发病和/或病程的基因，或已被报道与CHD有关的基因与CAD和临床事件的关系。因此，该项目的另一个目标是与项目1、2和3合作，以确定CATHGEN样本中与CAD或临床事件相关的任何基因变异是否也与其样本中的CVD内表型、高血压和/或T2D相关。与项目3一样，该项目提供了采取关键步骤的机会，将与心血管疾病内表型相关的基因转化为记录在案的对疾病终点的影响。

The overarching objective of this Project is to identify genetic variants that are associated, both as main effects and via interactions with exposure to environmental stressors, with incident cardiovascular events or coronary artery disease (CAD). To accomplish this goal, we will evaluate genes found associated in Projects 1 and 2 with CVD endophenotypes or in Project 3 with hypertension or type II diabetes (T2D), for associations with incident cardiovascular events and angiographically documented CAD in the CATHGEN sample of approximately 10,000 patients who have undergone cardiac catheterization at Duke since 2001. CATHGEN is a unique resource of biological samples collected at time of cardiac catheterization combined with a carefully adjudicated clinical database comprising angiographically-defined extent and anatomical distribution of coronary artery disease, extensive clinical data on CHD risk factors, and annual follow-up for evaluation of incident cardiovascular events. The CATHGEN investigators, under non-overlapping support from their NHLBI grant, will be evaluating a broad range of genes that are biologically plausible contributors to CHD pathogenesis and/or course or have been reported to be associated with CHD for associations with CAD and clinical events. Therefore, another aim of this Project, will be to collaborate with Projects 1, 2 and 3 to determine whether any genetic variants we fmd associated with CAD or clinical events in the CATHGEN sample are also associated with CVD endophenotypes, hypertension and/or T2D in their samples. As with Project 3, this Project provides the opportunity to take the critical step of translating gene associations with CVD endophenotypes into documented impact on disease endpoints.