Identifying and applying genetic variation relevant to clinical outcomes for individuals with congenital heart disease

项目概要 先天性心脏病 (CHD) 儿童的外科和医疗护理的改善 提高了生存率。然而，在幸存者中，这种情况的患病率很高，而且意义重大。 认知和行为问题以及医疗并发症的长期影响，包括 心力衰竭和生长问题。我们假设在某些 CHD 病例中， 对其他系统的发育和功能具有多效性影响的基因，包括 大脑。本研究的目的是确定遗传对临床结果的贡献 患有 CHD 的个人并开始在临床护理中使用这些信息并设计更好的 CHD 治疗的临床试验。通过这些研究，我们将确定主要的遗传因素 冠心病结果的贡献者，通过额外的病例发现扩大科学证据 在 PCGC 之外增加已确诊的 CHD 基因的数量并进行临床表征 这些遗传条件可以提高预测和预防医疗问题的能力 那些冠心病患者。通过识别先前临床中具有致病性变异的个体 试验，我们将确定基因组数据的整合是否会提高功效和精度 通过排除不太可能产生反应的患者组来进行冠心病治疗试验。所有这些努力 专注于将 PCGC 的研究结果转化为临床护理。

Project Summary Improvements in the surgical and medical care of children with congenital heart disease (CHD) have increased survival. Among survivors, however, there is a high prevalence and significant long term impact of cognitive and behavioral problems and medical complications including heart failure and problems with growth. We hypothesize that in some cases of CHD, there are genes that have pleiotropic effects on development and function of other systems including the brain. The goal of this study is to determine the genetic contributions to clinical outcomes in individuals with CHD and to begin to use this information in clinical care and to design better clinical trials of treatments for CHD. Through these studies, we will determine major genetic contributors to CHD outcomes, expand the scientific evidence through additional case finding outside of PCGC to increase the number of confirmed CHD genes and clinically characterize these genetic conditions to improve the ability to anticipate and prevent medical problems in those CHD patients. By identifying individuals with pathogenic variants from previous clinical trials, we will determine whether integration of genomic data would improve power and precision for CHD treatment trials by eliminating groups of patients unlikely to respond. All of these efforts are focused on translating the findings from PCGC into clinical care.