PHENOTYPIC AND GENETIC RISK FACTORS IN CONGENITAL CARDIOVASCULAR DISEASE

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。这项研究的目的是确定在儿童医院接受随访的CHD患者的表型，并确定可能与先天性心血管疾病相关的已知和新基因的多态。从历史上看，我们将调查环境和非心脏因素，这些因素可能会导致先天性心脏病的发生，从而在寻找疾病相关基因多态时起到混杂因素的作用。主要目的：D.评估CHD与所选候选基因之间的遗传关联。假设：我们预计CHD将与一个或多个已知的候选基因(如NKX2、TBX5等)相关。此外，可能还会发现在先天性心脏病的发病过程中发挥作用的新基因，这些基因以前并未被认识到。次要目的：1.在样本中有合理数量的家系中有多个家庭成员患有冠心病的情况下，进行全基因组连锁扫描。(这可以通过积极的心血管遗传学登记协议中的任何一种进行。在这项研究中，这不是预期中的事件。)此外，我们还将调查环境风险因素，包括母亲先孕和产前风险因素，这些因素可能有助于CHD的发展。这些数据对解释已识别的多态的意义很重要，特别是在已知的多因素疾病中。这些数据将是历史性的，并受到回忆偏差的影响。在这项研究中不会对其进行正式分析。根据这类轶事数据产生的任何假设都需要正式的单独调查，以确保有效性。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The goal of this study is to define phenotype in patients with CHD followed at Children's Hospital and to identify polymorphisms in known and novel genes that may be associated with congenital cardiovascular disease. By history we will survey for environmental and non-cardiac factors which may predispose to the development of congenital heart disease and thus act as confounders in the search for disease associated polymorphisms. Primary Aim: D. I. To evaluate the genetic association between CHD and selected candidate genes. Hypotheses: We anticipate that CHD will be associated with one or more known candidate genes (such as NKX2, TBX5, etc). Additionally, novel genes may be identified not previously recognized in playing a role in the development of congenital heart disease. Secondary Aim: I. To conduct a genome-wide linkage scan in the event that there are a reasonable number of families in the sample with multiple family members affected with CHD. (This could be undertaken through either of the active Cardiovascular genetics registry protocols. It is not an anticipated event in this study.) Additionally, we will survey for environmental risk factors, including maternal preconception and prenatal risk factors, which may contribute to the development of CHD. This data is important in interpreting significance of identified polymorphisms, particularly in diseases known to be multifactorial. This data will be historical and subject to recall bias. It will not be formally analyzed in this study. Any hypotheses generated from anecdotal data of this type will require formal separate investigation designed to ensure validity.