Survival and Age Biases in Gene Associations with Coronary Disease

描述(由申请人提供)：这是NIH独立职业发展之路奖(#1K99 NR011054-01)的重新提交。这一奖项的候选人是Jennifer R.Dungan，博士，RN，杜克大学护理学院和杜克老龄中心的高级研究员/John A.Hartford初级教员。威廉·E·克劳斯博士、伊丽莎白·R·豪泽博士、斯瓦蒂·H·沙阿博士和凯瑟琳·L·吉利斯博士将在该奖项的指导阶段担任共同导师。这项提案的首要目标是为候选人建立一个关于冠状动脉疾病生存遗传学的研究计划，这个研究计划结合了她在衰老、心血管疾病和遗传学方面的兴趣。邓根博士在现有的两个数据库(杜克大学导管化遗传学[CATHGEN]和弗雷明翰心脏研究)中建立了冠状动脉疾病存活率的表型，并进行了试点分析，以确定这些数据集中的存活率和年龄偏见。为了有效地研究冠状动脉疾病的生存遗传学，有必要首先了解生存和年龄偏差对与冠状动脉疾病相关的基因的影响以及对其影响的控制。她提出的指导性研究试图在两个数据集中广泛地表征这些偏见，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这些偏见。独立阶段研究试图确定其他流行病学数据集，以进一步确定此类偏见的范围，并测试指导阶段的统计方法。这些目标的结果将为冠状动脉疾病生存遗传学的前瞻性、流行病学调查(最终独立阶段目标)的试点研究的适当发展提供信息。邓根博士的培训计划包括加强她在遗传流行病学、统计遗传学和对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个竞争领域的未来生产力和潜力。其目标是通过这项研究，可以更好地筛选和识别心脏病患者的遗传风险和/或保护性基因，从而潜在地预防心脏病相关事件并促进健康生存。 公共卫生相关性： 许多基因已被确定为心脏病的致病基因。基因变异的影响可能会因年龄而异，我们检测这些影响的能力可能会受到研究中幸存下来的人的影响。如果存在与心脏病生存相关的基因，它们可能对了解心脏病发作和死亡的风险很重要，也可以提供关于防止这些风险的基因保护的信息。这项研究可能有助于改善心脏病患者的健康状况和存活率。

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.