Using genetic variation to study biology of blood lipids & coronary heart disease

摘要 二尖瓣脱垂（MVP）是一种常见但未被充分认识的疾病， and mortality.目前的治疗仅包括监测和手术。尽管基因组特征- 信息化已成为一种工具，用于确定药物目标的优先顺序和改善风险预测， 与许多心血管特征相比，MVP分析的效力相对不足， 识别.这项行政补充的目标是研究MVP的遗传学，使用一个大的- 对超过18，000例MVP病例进行大规模全基因组关联研究。我们的研究团队 在心血管医学，统计遗传学，高通量遗传学和遗传学方面的优势， 经济学在目标1中，我们将开发基于自然语言处理的MVP和MVP定义 亚表型，以提高案件鉴定。然后我们将完成一个全基因组关联 MVP和MVP亚表型的研究。在目标2中，我们将开发一个多基因风险评分框架 对MVP患者的心源性猝死风险进行分层。本行政补充 将利用我们通过全球脂质遗传学联盟（GLGC）建立的基础设施， 以及我们建立的合作关系。我们的目标的完成将提供新的见解， 有可能促进MVP预防、治疗和诊断方面的突破。

Abstract Mitral valve prolapse (MVP) is a common yet underrecognized condition carrying significant morbidity and mortality. Current management only includes surveillance and surgery. While genomic character- ization has emerged as a tool to prioritize targets for medicines and improve risk prediction, such analyses for MVP are relatively underpowered compared to many cardiovascular traits due to under recognition. The goal of this administrative supplement is to study the genetics of MVP using a large- scale genome-wide association study of over 18,000 MVP cases. Our research team combines strengths in cardiovascular medicine, statistical genetics, and high-throughput genetics and ge- nomics. In Aim 1, we will develop a natural-language processing-based definition of MVP and MVP sub-phenotypes to improve case identification. We will then complete a genome-wide association study of MVP and MVP sub-phenotypes. In Aim 2, we will develop a polygenic risk score framework to stratify risk of sudden cardiac death among individuals with MVP. This administrative supplement will leverage the infrastructure we have built through the Global Lipids Genetics Consortium (GLGC) and our established collaborative relationships. Completion of our aims will provide new insights that have the potential to catalyze breakthroughs in prevention, treatment, and diagnosis of MVP.