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

识别和应用与先天性心脏病患者临床结果相关的遗传变异

基本信息

批准号：
10028016
负责人：
Wendy K Chung
金额：
$ 47.04万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-01 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10028016
关键词：
Affect Age Anatomy Aneuploidy Arrhythmia Brain Candidate Disease Gene Cardiac Cardiac Death Cardiovascular system Caring Child Care Clinical Clinical Research Clinical Treatment Clinical Trials Clinical Trials Design Cognitive Collaborations DNA Data Databases Development Diagnostic Disease Outcome Down Syndrome Enrollment Etiology Exercise Family Funding Gap Junctions Genes Genetic Genetic Diseases Genetic Variation Genotype Goals Growth Heart failure Height High Prevalence Individual Inherited Intervention Laboratories Medical Medical Records Modeling Molecular Genetics Morbidity - disease rate Motion Neurodevelopmental Disorder Operative Surgical Procedures Other Genetics Outcome Pathogenicity Patients Pediatric Cardiac Genomics Consortium Phenotype Problem behavior Randomized Clinical Trials Reporting Risk Risk Estimate Role Site Socioeconomic Status Standardization Statistical Methods Survivors Syndrome System Testing Therapeutic Training Translating Transplantation Update Variant Ventricular Function base biobank blind case finding clinical care cohort congenital heart disorder design digital disease diagnosis exome sequencing genetic approach genetic association genetic variant genome sequencing genomic data improved improved outcome indexing individual patient insight instrument medical complication mortality neurodevelopment novel novel therapeutics outcome prediction pleiotropism polygenic risk score population based premature prevent proband programs prospective treatment trial

项目摘要

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.

项目摘要先天性心脏病（CHD）儿童的手术和医疗护理改善增加了生存。然而，在幸存者中，存在较高的流行率和显着认知和行为问题以及医疗并发症的长期影响，包括心力衰竭和成长问题。我们假设在某些CHD中，有对其他系统的发展和功能具有多效影响的基因脑。这项研究的目的是确定对临床结果的遗传贡献患有CHD的人，开始在临床护理中使用此信息并更好地设计 CHD治疗的临床试验。通过这些研究，我们将确定主要的遗传冠心病结果的贡献者，通过其他案例发现扩大科学证据在PCGC之外增加确认的CHD基因的数量并在临床上表征这些遗传条件以提高预期和防止医疗问题的能力那些冠心病患者。通过鉴定从以前的临床中识别患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率和精度对于CHD治疗试验，消除了不太可能做出反应的患者组。所有这些努力专注于将PCGC的发现转化为临床护理。