Genetic determinants of cardiac repolarization

心脏复极的遗传决定因素

基本信息

批准号：
7228133
负责人：
Christopher Holmes Newton-Cheh
金额：
$ 15.93万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-05-01 至 2010-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7228133
关键词：
Address Affect Arrhythmia Beta Adrenergic Receptor Gene Candidate Disease Gene Cardiac Cardiovascular Diseases Cardiovascular system Cessation of life Cisapride Collaborations Complex Congestive Heart Failure DNA Resequencing Development Plans Diabetes Mellitus Educational Curriculum Electrocardiogram Epidemiologist Exons Family Framingham Heart Study General Hospitals General Population Genes Genetic Genetic Determinism Genetic Variation Genome Genomics Genotype Goals Haplotypes Individual Institutes Ion Channel K-Series Research Career Programs Lead Long QT Syndrome Maps Massachusetts Medicine Mentors Mentorship Myocardial Numbers Participant Pharmaceutical Preparations Phenotype Population Preparation Range Research Research Personnel Research Proposals Retrospective Studies Risk Risk Factors Sampling Science Single Nucleotide Polymorphism Societies Structure Study Subject Subgroup Sudden Death Testing Time Torsades de Pointes Training Universities Variant Withdrawal base beta-adrenergic receptor career case control cost defined contribution genetic epidemiology genetic resource genetic risk factor genetic variant genome wide association study improved insight instructor medical schools member novel patient oriented research programs response skills sudden cardiac death trait

项目摘要

DESCRIPTION (provided by applicant): Dr. Christopher Newton-Cheh is a cardiologist at the Massachusetts General Hospital and Instructor in Medicine at Harvard Medical School. The candidate's long-term goal is to develop an independent career as a genetic epidemiologist defining the contribution of genetics to common cardiovascular disease. As a fellow at the Broad Institute of Harvard and MIT (Bl) and the Framingham Heart Study (FHS), the candidate has studied the genetic determinants of electrocardiographic QT interval variation in an effort to better understand myocardial repolarization in the general population and to identify potential genetic risk factors for sudden death and drug-induced torsade de pointes. The proposed career development plan involves a well-defined mentored patient-oriented research proposal to extend these studies, in concert with a structured didactic curriculum of advanced statistical, epidemiologic and genetic coursework. Under the mentorship of Dr. Joel Hirschhorn and Dr. Christopher O'Donnell, Dr. Newton-Cheh has made significant progress defining the common genetic variation in several candidate genes associated with the congenital Long QT Syndrome. The proposed projects will achieve the following specific aims: 1) to complete candidate gene association studies of QT interval variation in 1811 FHS subjects, 2) to determine whether rarer variants identified by resequencing candidate genes in FHS subjects contribute to extreme QT interval prolongation and 3) to carry out genome-wide association studies of QT interval duration using 220,000 single nucleotide polymorphisms being genotyped in 2000 members of a South Pacific population isolate through an existing collaboration with investigators at Rockefeller University. These studies will provide the most comprehensive assessment of the genetic determination of myocardial repolarization in the general population to date. Through the proposed research and educational training, Dr. Newton-Cheh will acquire the skills needed to pursue independent cardiovascular research at the cutting edge of genomic science.

描述（由申请人提供）： Christopher Newton-Cheh 博士是马萨诸塞州总医院的心脏病专家和哈佛医学院的医学讲师。候选人的长期目标是作为一名遗传流行病学家发展独立的职业生涯，定义遗传学对常见心血管疾病的贡献。作为哈佛大学和麻省理工学院博德研究所 (Bl) 和弗雷明汉心脏研究 (FHS) 的研究员，该候选人研究了心电图 QT 间期变异的遗传决定因素，以更好地了解一般人群的心肌复极并确定猝死和药物引起的尖端扭转型室性心动过速的潜在遗传风险因素。拟议的职业发展计划包括一项明确的、以患者为导向的指导性研究计划，以扩展这些研究，并与高级统计、流行病学和遗传学课程的结构化教学课程相结合。在 Joel Hirschhorn 博士和 Christopher O'Donnell 博士的指导下，Newton-Cheh 博士在定义与先天性长 QT 综合征相关的几个候选基因的常见遗传变异方面取得了重大进展。拟议的项目将实现以下具体目标：1) 完成 1811 名 FHS 受试者 QT 间期变异的候选基因关联研究，2) 确定通过对 FHS 受试者中的候选基因重新测序鉴定出的更罕见变异是否会导致 QT 间期极端延长，3) ）利用通过现有合作对南太平洋人群分离株的 2000 名成员进行基因分型的 220,000 个单核苷酸多态性进行 QT 间期持续时间的全基因组关联研究与洛克菲勒大学的研究人员合作。这些研究将为普通人群中心肌复极的遗传决定提供迄今为止最全面的评估。通过拟议的研究和教育培训，Newton-Cheh 博士将获得在基因组科学前沿进行独立心血管研究所需的技能。