A Phenome-Wide Association Study to Identify and Characterize Phenotypic Effects of Lp(a)

用于识别和表征 Lp(a) 表型效应的全表型关联研究

• 批准号: 10457031
• 负责人: Moa Park Lee
• 金额: $ 3.86万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-06 至 2022-01-05
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10457031
• 关键词: Address; Adult; Affect; African American; Algorithms; American; Architecture; Atherosclerosis; Attention; Biology; Biometry; Cardiometabolic Disease; Cardiovascular Diseases; Cardiovascular system; Clinical; Competence; Computer software; Computerized Medical Record; Data; Disease; Doctor of Pharmacy; Elderly; Ensure; Environment; Epidemiologist; Epidemiology; Ethnic group; European; Fellowship; Female; Foundations; Genetic; Genome; Genomics; Gills; Goals; Health; Heart failure; Hepatic; Heritability; Hispanics; Instruction; Interdisciplinary Study; Intervention; Investigation; Kidney; Kidney Diseases; Knowledge; LDL Cholesterol Lipoproteins; Latino; Link; Lipoprotein (a); Lipoproteins; Liver diseases; Low-Density Lipoproteins; Malignant Neoplasms; Measurement; Mentors; Modeling; Morbidity - disease rate; Myocardial Infarction; National Research Service Awards; Non-Insulin-Dependent Diabetes Mellitus; North Carolina; Outcome; Parents; Pathogenesis; Pathway interactions; Pharmacoepidemiology; Pharmacogenomics; Pharmacy (field); Pharmacy facility; Phenotype; Population; Positioning Attribute; Postdoctoral Fellow; Prevention; Prevention strategy; Public Health; Reporting; Research; Research Personnel; Research Project Grants; Research Training; Risk; Risk Factors; Role; Schools; Single Nucleotide Polymorphism; Solid; Source; Stroke; Training; United States National Institutes of Health; Universities; base; biobank; cardiometabolism; cardiovascular disorder epidemiology; cardiovascular disorder prevention; career; career development; data registry; density; design; disability; disease classification; disease phenotype; doctoral student; drug repurposing; ethnic minority population; experience; falls; genetic architecture; genetic epidemiology; genome wide association study; improved; innovation; insight; knowledge base; malignant breast neoplasm; mortality; multi-ethnic; multidisciplinary; new therapeutic target; novel; novel strategies; optimal treatments; phenome; phenotypic data; population health; prevent; racial and ethnic; side effect; skills; statistics; therapeutic candidate; trait; treatment strategy; venous thromboembolism; young adult

Project Summary/Abstract This NIH Kirschstein-NRSA postdoctoral fellowship (F32) application is designed to promote the training of Dr. Moa Lee, PharmD, MPH, a post-doctoral fellow and concurrent Epidemiology PhD student at the University of North Carolina, and to provide her with the foundation for an independent research career. Building upon her clinical training and research experience in the fields of pharmacy and pharmacoepidemiology, Dr. Lee's goal is to expand her research horizon into pharmacogenomics research under the sponsorship of two highly successful genetic epidemiologists. This advanced training will enable Dr. Lee to further contribute to advancing the clinical knowledge and research base underlying optimal treatment decisions. The proposed research project is deliberately designed to leverage Dr. Lee's research experience using dense phenotypic data while providing extensive training to acquire the remaining competencies in genetic epidemiology and career development. Driven by the need to improve current prevention and treatment strategies for cardiovascular disease (CVD), Dr. Lee will interrogate lipoprotein (a) [Lp(a)]. Emerging evidence has identified Lp(a), a highly atherogenic, low density lipoprotein-like moiety, as an attractive novel therapeutic target. Given that the current understanding of the role of Lp(a) in CVD is limited, particularly with respect to emerging evidence that Lp(a) may affect a broader range of phenotypes, the proposed research will comprehensively interrogate the effects of Lp(a) on health and disease. Specifically, Dr. Lee proposes a phenome-wide association study (PheWAS) of Lp(a), a novel approach to assess the effects of Lp(a) across a broad range of phenotype domains. By helping ensure temporality in exposure effects and limiting bias from confounding, a Lp(a) PheWAS is uniquely positioned to provide new insights into the underlying pathogenesis of Lp(a), uncover novel associations, and, ultimately, inform understanding unanticipated side effects of potential treatments. Dr. Lee's deliberate selection of a large (n~600,000), deeply phenotyped, multi-ethnic population spanning early to late adulthood with a large proportion of females will increase the generalizability of study findings. Together, this proposal will provide Dr. Lee with a solid foundation in genetic epidemiology. The knowledge and experience as well as the preliminary data afforded by this proposal will provide the groundwork for Dr. Lee's future research agenda as well as investigator-initiated applications as she embarks on an independent and interdisciplinary research career.

项目总结/摘要 这个NIH Kirschstein-NRSA博士后奖学金（F32）应用程序旨在促进博士的培训。 Moa Lee，药学博士，公共卫生硕士，博士后研究员，同时在纽约大学攻读流行病学博士学位。 北卡罗来纳州，并为她提供独立研究生涯的基础。在她的基础上 在药学和药物流行病学领域的临床培训和研究经验，李博士的目标是 在两个非常成功的赞助下，将她的研究视野扩展到药物基因组学研究 遗传流行病学家这种先进的培训将使李博士能够进一步促进临床 最佳治疗决策的基础知识和研究。拟议的研究项目是 刻意设计，以利用李博士的研究经验，使用密集的表型数据，同时提供 广泛的培训，以获得遗传流行病学和职业发展方面的剩余能力。 由于需要改善目前的心血管疾病（CVD）预防和治疗策略， 李将询问脂蛋白（a）[Lp（a）]。新出现的证据已经确定Lp（a）是一种高度致动脉粥样硬化、低 密度脂蛋白样部分，作为一个有吸引力的新的治疗靶点。鉴于目前对 Lp（a）在CVD中的作用是有限的，特别是关于新出现的证据表明Lp（a）可能影响更广泛的 一系列表型，拟议的研究将全面询问Lp（a）对健康的影响， 疾病具体来说，Lee博士提出了Lp（a）的全表型关联研究（PheWAS），这是一种新的方法。 评估Lp（a）在广泛表型域中的作用。通过帮助确保 暴露效应和限制混杂偏倚，Lp（a）PheWAS独特地定位于提供新的 深入了解Lp（a）的潜在发病机制，发现新的关联，并最终告知 了解潜在治疗的意外副作用。李博士精心挑选了一个大的 （n~ 600，000），表型很深，多种族人群，从成年早期到成年晚期， 女性的比例将增加研究结果的普遍性。总之，这项建议将为李博士提供一个 遗传流行病学的坚实基础。提供的知识和经验以及初步数据 这一提议将为李博士未来的研究议程以及由财政部发起的 申请，因为她开始了独立和跨学科的研究生涯。