CHD Risk and Metabolomic Profiles of Discordant Lipids

冠心病风险和不一致脂质的代谢组学特征

• 批准号: 9223043
• 负责人: Olga Demler
• 金额: $ 16.13万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-15 至 2021-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9223043
• 关键词: Address; African American; Alpha Particles; Apolipoproteins B; Area; Atherosclerosis; Award; Big Data; Biological Assay; Biological Markers; Biometry; Boston; Cardiovascular Diseases; Cardiovascular system; Cholesterol; Clinical; Collaborations; Complex; Coronary heart disease; Data; Data Set; Development; Disease; Disease Outcome; Environment; Epidemiology; Event; Future; Genotype; Goals; High Density Lipoprotein Cholesterol; Hospitals; Human; Incidence; Individual; Institution; Interdisciplinary Study; Knowledge; LDL Cholesterol Lipoproteins; Lead; Learning; Lipids; Low-Density Lipoproteins; Mass Spectrum Analysis; Measurement; Measures; Medical Research; Mentored Research Scientist Development Award; Mentors; Mentorship; Metabolic; Omega-3 Fatty Acids; Outcome; Pathogenesis; Pathway Analysis; Phenotype; Plasma; Prevention; Preventive; Public Health; Publications; Publishing; Reporting; Research; Research Methodology; Research Personnel; Research Project Grants; Research Training; Residual state; Risk; Risk Factors; Software Tools; Statistical Data Interpretation; Statistical Methods; Techniques; Testing; Text; Training; Training Programs; Universities; Vitamin D; Woman; Women' s Health; career; career development; clinical phenotype; cohort; design; disorder risk; experience; follow-up; high risk; improved; insight; interest; male; men; metabolic phenotype; metabolomics; novel; particle; predictive modeling; public health relevance; skills; small molecule; statistics; targeted treatment; therapeutic development; therapeutic target

Project Number: Contact PI / Project Leader: DEMLER, OLGA Title: CHD RISK AND METABOLOMIC PROFILES OF DISCORDANT LIPIDS Awardee Organization: BRIGHAM AND WOMEN'S HOSPITAL Abstract Text: DESCRIPTION (provided by applicant): The primary objective of this proposal is to create a multidisciplinary research and training environment that will provide the candidate, Dr. Olga Demler, with knowledge and experience necessary to launch a successful career as an independent researcher in the statistical analysis of metabolomics data with the focus on lipidomics and cardiovascular outcomes. The training program builds upon the candidate's background in methodological research in biostatistics and risk prediction modelling and is focused on learning lipidomics and advanced statistical techniques that are used in targeted, untargeted and network pathway analyses of metabolomics data. This application is supported by a team of established mentors and by a strong institutional commitment of a leading research hospital which is part of a network of Boston-area universities and institutions with abundant opportunities to learn about cutting edge medical research, and to build cross- disciplinary collaborations. The research goal of this proposal is to define lipid profiles that best predict the risk of coronary heart disease (CHD) and to characterize their metabolomic signatures. Low-density lipoprotein (LDL) particles are a causal biomarker in the development of atherosclerosis and CHD. Yet recent studies reported that there is residual lipid-related risk information beyond standard lipid biomarkers. Dr. Demler will extend the standard lipid panel and use additional lipid parameters such as non-high density lipoprotein cholesterol, apolipoprotein B (apoB), and LDL particle concentration, among others. Of special interest are the individuals with discordant combinations of LDL-C and apoB (e.g. low LDL-C, but higher than expected apoB), a group that has substantially higher CHD risk than those with concordant combination of the two parameters even after controlling for LDL-C level and standard risk factors. First, in the Women's Health Study, Dr. Demler will find the most informative combinations of lipid parameters and discordant lipids that best predict CHD events. She will validate these findings in a more demographically diverse VITAL cohort. Second, Dr. Demler will characterize the metabolomic profiles of lipids and lipid combinations including discordant lipids associated with CHD in the VITAL metabolomic sub-study, using state-of-the-art statistical techniques in untargeted, and network metabolomic analyses. This project leverages the candidate's strong background in risk prediction and combines an outstanding research and training environment with already collected CHD outcomes, lipid measurements, and large-scale metabolomics data, providing a unique opportunity to the candidate to gain skills and experience necessary for her career as an independent researcher in statistical analysis of metabolomics/lipidomics data in cardiovascular diseases. The knowledge gained from this project will increase our understanding of specific metabolic mechanisms that govern the association between wide array of lipid measures and CHD by identifying their underlying metabolic dysregulation. Thus, it will address important public health issues and could provide insight into disease pathogenesis and potential development of therapeutic targets.

项目编号：联系PI /项目负责人：DEMLER，OLGA 标题：CHD风险和不一致脂质的代谢特征 获奖机构：Brigham AND Women's Hospital 摘要文本： 描述（由申请人提供）： 这项建议的主要目标是创造一个多学科的研究和培训环境， 为候选人Olga Demler博士提供成功开展 作为代谢组学数据统计分析的独立研究员，专注于 脂质组学和心血管结局。该培训计划建立在候选人的背景， 生物统计学和风险预测建模的方法研究，重点是学习脂质组学， 先进的统计技术，用于目标，非目标和网络途径分析， 代谢组学数据。这个应用程序是由一个既定的导师团队和强大的机构支持 一家领先的研究型医院的承诺，这是波士顿地区大学网络的一部分， 机构拥有丰富的机会，了解尖端的医学研究，并建立跨 纪律合作。这项提案的研究目标是确定最能预测风险的血脂谱。 冠状动脉心脏病（CHD），并表征其代谢组学特征。低密度脂蛋白 (LDL)颗粒是动脉粥样硬化和CHD发展中的因果生物标志物。然而最近的研究 报告称，除了标准脂质生物标志物外，还有剩余的脂质相关风险信息。德姆勒博士将 扩展标准血脂检查，并使用其他血脂参数，如非高密度脂蛋白 胆固醇、载脂蛋白B（apo B）和LDL颗粒浓度等。特别值得注意的是 LDL-C和apoB组合不一致的个体（例如，低LDL-C，但高于预期的apoB）， CHD风险显著高于两个参数一致组合的人群 即使在控制了LDL-C水平和标准风险因素之后。首先，在女性健康研究中， 将找到最能预测冠心病的血脂参数和不一致血脂的最具信息量的组合 事件她将在人口统计学上更加多样化的VITAL队列中验证这些发现。第二，德姆勒博士 将描述脂质和脂质组合的代谢组学特征，包括与脂质相关的不一致脂质 VITAL代谢组学子研究中的CHD患者，在非靶向研究中使用最先进的统计技术，以及 网络代谢组学分析该项目利用候选人在风险预测方面的强大背景， 将出色的研究和培训环境与已经收集的CHD结果相结合， 测量和大规模代谢组学数据，为候选人提供了一个独特的机会， 作为一名独立的统计分析研究员，她的职业生涯所必需的技能和经验， 心血管疾病的代谢组学/脂质组学数据。从这个项目中获得的知识将增加 我们对特定代谢机制的理解，这些机制控制着各种脂质之间的联系， 通过确定其潜在的代谢失调来测量和CHD。因此，它将解决重要的 公共卫生问题，并可以提供深入了解疾病的发病机制和潜在的发展， 治疗目标