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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

基本信息

批准号：
10063022
负责人：
Olga Demler
金额：
$ 17.82万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-12-15 至 2022-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10063022
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 Development Disease Disease Outcome Environment 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&apos s Health cardiovascular disorder epidemiology career career development clinical phenotype cohort design experience follow-up heart disease risk high risk improved insight interest large scale data lipidomics male men metabolic phenotype metabolomics novel particle public health relevance risk prediction risk prediction model skills small molecule sociodemographics statistics targeted treatment therapeutic development therapeutic target

项目摘要

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：冠心病风险和不协调脂类的代谢谱获奖者组织：布里格姆妇女医院摘要正文：描述(由申请人提供)：这项提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博士提供必要的知识和经验，以启动成功的作为代谢组学数据统计分析的独立研究员，专注于脂类组学与心血管疾病结局。培训计划建立在应聘者在生物统计学和风险预测建模的方法学研究，专注于学习脂质组学和用于目标、非目标和网络路径分析的高级统计技术代谢组学数据。此应用程序由一组成熟的导师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，有大量机会学习尖端医学研究的机构，并建立交叉纪律协作。这项建议的研究目标是定义最能预测风险的血脂分布目的是研究冠心病(CHD)的遗传易感性，并描述其代谢特征。低密度脂蛋白低密度脂蛋白(LDL)颗粒是动脉粥样硬化和冠心病发生发展的致病生物标志物。然而，最近的研究报道称，除了标准的脂类生物标志物外，还有剩余的脂类相关风险信息。德姆勒博士会扩展标准脂类面板并使用其他脂类参数，如非高密度脂蛋白胆固醇、载脂蛋白B(ApoB)和低密度脂蛋白颗粒浓度等。特别值得关注的是低密度脂蛋白胆固醇和载脂蛋白B组合不协调的个体(例如低密度脂蛋白胆固醇，但高于预期的载脂蛋白B)，与两个参数协调组合的人群相比，冠心病风险显著更高的人群即使在控制了低密度脂蛋白水平和标准危险因素之后。首先，在女性健康研究中，德姆勒博士将找到最能预测冠心病的脂类参数和不协调脂类的信息量最大的组合事件。她将在人口统计学上更加多样化的重要队列中验证这些发现。第二，德姆勒博士将表征脂类和脂类组合的代谢谱，包括与不协调的脂类相关的在重要代谢组子研究中使用最先进的统计技术在非靶向，以及网络代谢组学分析。该项目充分利用了应聘者在风险预测和将卓越的研究和培训环境与已经收集的CHD结果、血脂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她作为一名统计分析独立研究员的职业生涯所需的技能和经验心血管疾病中的代谢组学/脂质组学数据。从这个项目中获得的知识将会增加我们对控制多种脂质之间联系的特定代谢机制的理解通过确定潜在的代谢失调来衡量和CHD。因此，它将处理重要的公共卫生问题，并可提供对疾病发病机制和潜在的发展的洞察治疗靶点。

项目成果

期刊论文数量（15）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Association of the Mediterranean Diet With Onset of Diabetes in the Women's Health Study.

DOI：
10.1001/jamanetworkopen.2020.25466
发表时间：
2020-11-02
期刊：
JAMA network open
影响因子：
13.8
作者：
Ahmad S;Demler OV;Sun Q;Moorthy MV;Li C;Lee IM;Ridker PM;Manson JE;Hu FB;Fall T;Chasman DI;Cheng S;Pradhan A;Mora S
通讯作者：
Mora S

Immunoglobulin G N-Glycosylation Signatures in Incident Type 2 Diabetes and Cardiovascular Disease.

DOI：
10.2337/dc22-0833
发表时间：
2022-11-01
期刊：
Diabetes care
影响因子：
16.2
作者：
通讯作者：

Association of Physical Activity With Bioactive Lipids and Cardiovascular Events.

DOI：
10.1161/circresaha.122.320952
发表时间：
2022-08-05
期刊：
CIRCULATION RESEARCH
影响因子：
20.1
作者：
Hoshi, Rosangela A.;Liu, Yanyan;Luttmann-Gibson, Heike;Tiwari, Saumya;Giulianini, Franco;Andres, Allen M.;Watrous, Jeramie D.;Cook, Nancy R.;Costenbader, Karen H.;Okereke, Olivia, I;Ridker, Paul M.;Manson, JoAnn E.;Lee, I-Min;Vinayagamoorthy, Manickavasagar;Cheng, Susan;Copeland, Trisha;Jain, Mohit;Chasman, Daniel, I;Demler, Olga, V;Mora, Samia
通讯作者：
Mora, Samia

Cholesterol Efflux Capacity, High-Density Lipoprotein Particle Number, and Incident Cardiovascular Events: An Analysis From the JUPITER Trial (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin).