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

项目摘要/摘要 NIH Kirschstein-NRSA博士后奖学金(F32)申请是为了促进博士的培训。 Moa Lee，药学博士，公共卫生硕士，博士后研究员，同时在加州大学攻读流行病学博士学位 北卡罗来纳州，并为她的独立研究事业提供了基础。在她的基础上建设 在药剂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 在两位非常成功的科学家的赞助下，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。这一高级培训将使李医生能够进一步为推动临床 最优治疗决策的基础知识和研究基础。建议的研究项目是 精心设计，利用Lee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。 在改善目前心血管疾病(CVD)预防和治疗策略的需要的推动下，Dr。 Lee将审问脂蛋白(A)[Lp(A)]。新出现的证据表明，Lp(A)是一种高度致动脉粥样硬化的低密度脂蛋白 密度脂蛋白样部分，作为一个有吸引力的新治疗靶点。鉴于目前对 Lp(A)在心血管疾病中的作用是有限的，特别是在新的证据表明Lp(A)可能影响更广泛的 一系列的表型，拟议的研究将全面询问Lp(A)对健康和 疾病。具体地说，Lee博士提出了一种新的方法，即Lp(A)的全组关联研究(Phewas 评估Lp(A)在广泛的表型结构域中的作用。通过帮助确保项目的暂时性 暴露效应和限制混杂的偏差，LP(A)Phewas是唯一能够提供新的 对脂蛋白(A)潜在发病机制的洞察，发现新的关联，并最终告知 了解潜在治疗的意外副作用。李博士深思熟虑地选择了一个 (n~60万)，表型深刻，多民族人口，年龄跨度从成年期早期到成年期晚期，占很大比例 女性的参与将增加研究结果的概括性。总而言之，这项提议将为李博士提供 扎实的遗传流行病学基础。所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研究人员发起的 随着她开始独立和跨学科的研究生涯，她开始了自己的应用程序。

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.