Survival and Age Biases in Gene Associations with Coronary Disease

与冠心病基因关联的生存和年龄偏差

• 批准号: 7787150
• 负责人: JENNIFER R DUNGAN
• 金额: $ 8.58万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-29 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7787150
• 关键词: Address; Age; Aging; Alleles; Area; Award; Biological Models; CAD gene; Candidate Disease Gene; Cardiovascular Diseases; Cardiovascular system; Catheterization; Cessation of life; Complex; Coronary Arteriosclerosis; Coronary heart disease; Data; Data Collection; Data Set; Databases; Development; Diabetes Mellitus; Disease; Disease Association; Doctor of Philosophy; Epidemiologic Studies; Epidemiology; Evaluation; Event; Faculty; Framingham Heart Study; Frequencies; Future; Gene Frequency; Gene Mutation; Genes; Genetic; Genetic Research; Genetic Risk; Genetic Variation; Genomics; Genotype; Goals; Health; Heart Diseases; Incidence; Individual; Investigation; K-Series Research Career Programs; Knowledge; Life; Linear Regressions; Literature; Longitudinal Studies; Measures; Mentors; Methods; Modeling; Modification; Myocardial Infarction; Natural History; Outcome; Pathway interactions; Patients; Pattern; Phase; Phenotype; Pilot Projects; Population; Postdoctoral Fellow; Prevalence; Productivity; Prospective Studies; Research; Research Design; Research Personnel; Research Project Grants; Research Proposals; Risk; Sample Size; School Nursing; Social Sciences; Statistical Methods; Statistical Models; Sudden Death; Survival Analysis; Survival Rate; Symptoms; Testing; Time; Training; United States National Institutes of Health; Universities; Woman; Work; age group; age related; base; design; disorder control; early onset; efficacy testing; experience; follow-up; genetic association; genetic epidemiology; genetic variant; heart disease prevention; high risk; improved; interest; knowledge base; longitudinal database; men; prevent; programs; prospective; public health relevance; sudden cardiac death; survivorship; tool

DESCRIPTION (provided by applicant): This is a resubmission for a NIH Pathway to Independence Career Development Award (# 1K99 NR011054- 01). The candidate for this award is Jennifer R. Dungan, PhD, RN, a Senior Research Associate at the Duke University School of Nursing and Duke Center for Aging/John A. Hartford Junior Faculty Fellow. Drs. William E. Kraus, Elizabeth R. Hauser, Svati H. Shah, and Catherine L. Gilliss will serve as co-mentors during the mentored phase of this award. The overarching goal of this proposal is for the candidate to build a research program in the genetics of survivorship in coronary artery disease, a research program that combines her interests in aging, cardiovascular disease, and genetics. Dr. Dungan has established the phenotype for survivorship in coronary artery disease in two existing databases (the Duke CATHeterization GENetics [CATHGEN] and the Framingham Heart studies) and has performed pilot analysis to identify survival and age biases in these datasets. In order to effectively study the genetics of survivorship in coronary artery disease, it is necessary to first understand the impact of survival and age biases on gene associations with coronary artery disease and control for their effects. Her proposed mentored research seeks to extensively characterize these biases in both datasets, then test traditional and complex statistical methods to control for such biases in gene associations with coronary artery disease. The independent phase research seeks to identify other epidemiological datasets to further characterize the scope of such biases and test the statistical methods from the mentored phase. Results from these aims will inform the proper development of a pilot study of a prospective, epidemiological investigation of the genetics of survivorship in coronary artery disease (final independent phase aim). Dr. Dungan's training plan includes strengthening her background in genetic epidemiology, statistical genetics, and statistical handling of time-related effects. Given the candidate's strong background in genetics and her experience with research projects in cardiovascular aging and genomics, a strong epidemiological and statistical knowledge base will enhance her future productivity and potential in this competitive field. The goal is that from this research, heart disease patients may be better screened and identified for genetic risk and/or protective genes, potentially leading to prevention of heart-disease-related events and promotion of healthy survival. PUBLIC HEALTH RELEVANCE: Many genes have been identified for heart disease. The impact of genetic variation may vary by age and our ability to detect these effects may be impacted by who survives to be in the study. If there are genes specifically related to surviving with heart disease, they may be important to understanding risk for heart attacks and death and can also provide information about genetic protection against these risks. This research may help improve health outcomes and survival for people with heart disease.

描述（由申请人提供）：这是NIH独立职业发展奖（#1 K99 NR 011054 - 01）的重新提交。该奖项的候选人是Jennifer R。Dungan博士，注册护士，杜克大学护理学院和杜克老龄化中心的高级研究助理/John A.哈特福德初级教职研究员。Drs. William E.伊丽莎白·克劳斯豪瑟，斯瓦蒂·H. Shah，and Catherine L. Gilliss将在该奖项的指导阶段担任共同导师。该提案的总体目标是为候选人建立一个冠状动脉疾病生存遗传学的研究计划，该研究计划结合了她对衰老，心血管疾病和遗传学的兴趣。Dungan博士在两个现有数据库（杜克CATHeterization GeNetics [CATHGEN]和Fraudulent Heart研究）中建立了冠状动脉疾病生存率的表型，并进行了初步分析，以确定这些数据集中的生存率和年龄偏倚。为了有效地研究冠状动脉疾病生存率的遗传学，有必要首先了解生存率和年龄偏倚对冠状动脉疾病相关基因的影响，并控制其影响。她提出的指导研究旨在广泛描述这两个数据集中的这些偏差，然后测试传统和复杂的统计方法，以控制与冠状动脉疾病相关的基因中的此类偏差。独立阶段的研究旨在确定其他流行病学数据集，以进一步表征此类偏倚的范围，并测试指导阶段的统计方法。这些目标的结果将为正确开展一项前瞻性、流行病学调查冠状动脉疾病生存遗传学的试点研究提供信息（最终独立阶段目标）。Dungan博士的培训计划包括加强她在遗传流行病学，统计遗传学和时间相关效应的统计处理方面的背景。鉴于候选人在遗传学方面的强大背景以及她在心血管衰老和基因组学研究项目方面的经验，强大的流行病学和统计学知识基础将提高她在这一竞争领域的未来生产力和潜力。这项研究的目的是，通过这项研究，心脏病患者可以更好地筛查和识别遗传风险和/或保护基因，从而可能预防心脏病相关事件并促进健康生存。 公共卫生关系： 许多基因已被确定为心脏病。遗传变异的影响可能因年龄而异，我们检测这些影响的能力可能会受到研究中幸存者的影响。如果有与心脏病生存有关的基因，它们可能对理解心脏病发作和死亡的风险很重要，也可以提供有关遗传保护的信息。这项研究可能有助于改善心脏病患者的健康状况和生存率。