Development of a cloud-based analytical tool for polygenic risk score and its implication in heart failure research.

摘要 本申请是对NIH特殊利益通知(NOT-OD-23-070)的行政补充： 用于支持NIH支持的研究中的云探索的管理补充。父项目 旨在阐明心脏结构和功能的遗传结构，以改善心力衰竭(HF) 使用为心脏结构和功能构建的多基因风险评分(PR)进行预测。HF随时间延长而增加 年龄明显增加，并与50%的5年死亡率有关。它是可遗传的；全基因组关联研究 已经确定了数十个心力衰竭的遗传位点，提示存在多基因遗传。PrS量化慢性病 来自多种基因变异的疾病易感性，这已经证明了定制的潜力 心血管疾病的临床干预。很少有研究探索PR对HF的作用。尽管包裹中的 已经开发了云计算平台建设，努力将资源转移到云平台，促进云化 托管大规模基因组数据的分析是有限的。对于这一行政补充，我们因此 目的：1)在云计算平台BioData Catalyst(BDC)上开发一个PRS构建和分析工具 由TOPMed计划指定，以及2)评估在预测心力衰竭发展方面的PRS的使用， 协作式云环境。它与父级奖项不同，因为父级奖项侧重于 心脏的结构和功能，而不是心衰，父母奖不包括开发基于云的 分析工具。这一补充也是对父奖项的补充，因为所建立的分析工具可以 促进家长奖的分析和高频社区计划的建立可以促进对高频的认识 病因学，与家长奖一致。这项补充工作的完成将为 基于BDC的工具开发，为BDC用户提供了用户友好的工具，并展示了 将遗传易感性纳入早期发现和预防心力衰竭，这是减少心力衰竭的关键步骤。 相关的发病率和死亡率。

ABSTRACT This application is an administrative supplement in response to NIH Notice of Special Interest (NOT-OD-23-070): Administrative Supplements to Support the Exploration of Cloud in NIH-supported Research. The parent project aims to elucidate the genetic architecture of cardiac structure and function and to improve heart failure (HF) prediction by using polygenic risk scores (PRS) constructed for cardiac structure and function. HF increases with age markedly and is associated with a 50% 5-year mortality. It is heritable; genome-wide association studies (GWAS) have identified scores of genetic loci for HF, suggesting polygenic inheritance. PRS quantifies chronic disease susceptibility stemming from multiple genetic variants, which has demonstrated the potential to tailor clinical intervention for cardiovascular disease. Few studies have explored PRS for HF. Although packages of PRS construction have been developed, the effort to transit resources to cloud platforms to facilitate cloud-based analyses, where large-scale genomic data are hosted, is limited. For this administrative supplement, we therefore aim to 1) develop a PRS construction and analyses tool on BioData Catalyst (BDC), a cloud computing platform designated by the TOPMed program, and 2) assess the use of PRS for predicting HF development, in a collaborative cloud environment. It is distinct from the parent award as the parent award focuses on PRS of cardiac structure and function, not HF, and the parent award doesn’t include effort to develop a cloud-based analytical tool. This supplement is also complementary to the parent award as the analytical tool built could facilitate the analyses of the parent award and the construction of HF PRS could advance of knowledge of HF etiology, in line with the parent award. The completion of this supplement will provide valuable experience for tools development on BDC, deliver a user-friendly tool for BDC users, and demonstrate the advantage of incorporating genetic susceptibility to early-detect and to prevent HF, an essential step in decreasing HF- associated morbidity and mortality.