Common Genetic Pathways Underlying CVD and COPD

 描述（由申请人提供）： 这是申请辅导研究科学家发展奖（父母K 01）的重新提交，Sharon Lutz博士是科罗拉多大学安舒茨医学院科罗拉多公共卫生学院（CSPH）的生物统计学助理教授。Lutz博士正在确立自己作为慢性阻塞性肺疾病（COPD）和心血管疾病（CVD）遗传重叠的年轻研究者的地位。该K 01奖项将为Lutz博士提供必要的支持，使其通过正式培训获得COPD和CVD重叠的病理生理学和流行病学的坚实基础知识，以便成为研究COPD和CVD常见遗传易感性的独立研究者。为了实现这一目标，Lutz博士组建了一个由流行病学导师John Hokanson博士和生物统计学导师Tasha Fingerlin博士组成的指导团队。Hokanson博士是CSPH的流行病学教授，也是国家心肺血液研究所（NHLBI）资助的COPDGene研究的流行病学中心主任。Fingerlin博士是CSPH的生物统计学副教授，也是National Jewish Health的基因、环境和健康中心主任。除了Lutz博士的主要导师外，还有两位顾问将为该项目服务：Christoph Lange博士，哈佛公共卫生学院的生物统计学教授，专门研究COPD的统计遗传学; Matthew Buffett博士，Harbor-UCLA医学中心的心脏病学教授，美国心脏协会（AHA）EBT和多层CT扫描仪科学声明的主席。CVD是COPD患者死亡的两个最常见原因之一。然而，COPD受试者独特的高CVD风险的炎症和遗传基础仍然未知。Lutz博士的研究将检查COPD基因研究（AIM 1）中通过FEV 1和FEV 1/FVC测量的COPD和通过冠状动脉钙（CAC）和胸主动脉钙（TAC）测量的CVD的遗传重叠。Lutz博士将开发统计方法来量化二元表型，2种以上表型和罕见变异之间的遗传重叠。(AIM 1）由于吸烟可能会影响COPD和CVD之间的遗传重叠，Lutz博士将在肺功能（FEV 1和FEV 1/FVC）和血管钙化（CAC和TAC）两项指标中检查基因与吸烟的相互作用。(AIM 2）由于基因与环境相互作用的标准方法往往动力不足，Lutz博士提出了一种用于基因与环境相互作用的贝叶斯方法，该方法利用已知的遗传信息并保持分层原则。(AIM 2）为了确定通过吸烟从基因到疾病的路径，Lutz博士将开发一种统计方法来确定罕见变异是否与吸烟间接相关。 肺功能（FEV 1和FEV 1/FVC）和血管钙化（CAC和TAC）。(AIM第三章

 DESCRIPTION (provided by applicant): This is a resubmission of the application for a Mentored Research Scientist Development Award (Parent K01) for Dr. Sharon Lutz, an Assistant Professor of Biostatistics at the Colorado School of Public Health (CSPH) at the University of Colorado, Anschutz Medical Campus. Dr. Lutz is establishing herself as a young investigator in the genetic overlap of Chronic Obstructive Pulmonary Disease (COPD) and Cardio Vascular Disease (CVD). This K01 award will provide Dr. Lutz with the support necessary to acquire a solid foundational knowledge of the pathophysiology and epidemiology of the overlap between COPD and CVD through formal training in order to become an independent investigator studying common genetic susceptibility for COPD and CVD. To achieve this goal, Dr. Lutz has assembled a mentoring team comprised of an Epidemiology mentor, Dr. John Hokanson, and a Biostatistics mentor, Dr. Tasha Fingerlin. Dr. Hokanson is a Professor of Epidemiology at CSPH and Director of the Epidemiology Center for the National Heart, Lung, and Blood Institute (NHLBI) funded COPDGene study. Dr. Fingerlin is an Associate Professor of Biostatistics at CSPH and director of the Center for Gene, Environment, and Health at National Jewish Health. In addition to Dr. Lutz's primary mentors, two consultants will serve on this project: Dr. Christoph Lange, a Professor of Biostatistics at Harvard School of Public Health who specializes in the statistical genetics of COPD and Dr. Matthew Budoff, a Professor of Cardiology at Harbor-UCLA Medical Center who is the chairman of the American Heart Association (AHA) Scientific Statement on EBT and Multi-slice CT Scanner. CVD is one of two most common causes of death in patients with COPD. However, the inflammatory and genetic basis for the uniquely high CVD risk in subjects with COPD remains unknown. Dr. Lutz's research will examine the genetic overlap of COPD as measured by FEV1 and FEV1/FVC and CVD as measured by coronary artery calcium (CAC) and thoracic aortic calcium (TAC) in the COPDGene study (AIM 1). Dr. Lutz will develop statistical methodology to quantify genetic overlap amongst binary phenotypes, more than 2 phenotypes, and rare variants. (AIM 1) Since smoking may influence the genetic overlap between COPD and CVD, Dr. Lutz will examine gene by smoking interactions in both measures of pulmonary function (FEV1 and FEV1/FVC) and vascular calcification (CAC and TAC). (AIM 2) Because standard methods for gene by environment interactions tend to be underpowered, Dr. Lutz proposes a Bayesian method for gene by environment interactions that leverages known genetic information and maintains the hierarchical principle. (AIM 2) To determine the path from gene to disease through smoking, Dr. Lutz will develop a statistical method to determine if rare variants are associated indirectly with pulmonary function (FEV1 and FEV1/FVC) and vascular calcification (CAC and TAC) through smoking. (AIM 3)