ASPirin in Reducing Events in the Elderly - eXTension

项目总结/摘要 基因组学已成为大型临床试验和队列研究的一个越来越重要的方面。基因组数据 调查环境和遗传因素对健康的共同作用的重要组成部分 衰老过程中的疾病然而，基因组信息的价值很少能通过分析 来自单一队列的数据。相反，来自多个队列的数据必须合并到一个联盟中， 达到发现新基因所需的统计能力。许多著名的基因组学联盟都涉及 来自许多不同NIH资助的队列的基因组数据的贡献，用于全基因组关联研究 （GWAS）和荟萃分析。例子包括基因组学中的心脏和衰老研究队列 流行病学（CHARGE）联盟、阿尔茨海默病遗传学联盟（ADGC）和阿尔茨海默病遗传学联盟（ADGC）。 疾病测序项目（ADSP）。我们的研究，ASPirin减少老年人事件（ASPREE）试验- 以及随后的观察性扩展研究（ASPREE-XT）-幸运地收集了 通过ASPREE健康老龄化生物样本库收集生物标本，并生成大多数参与者的基因组数据 （约15，000名健康老年人，具有靶向测序和全基因组SNP数据）。这些信息是 现在，我们的U19 AG 062682在确定生活方式的相对和联合影响方面的工作具有重要价值， 基因组学和环境对老年人健康的影响。基因组数据集的可用性 也为ASPREE-XT进入基因组学联盟提供了最近的机会和必要性， 基因发现的努力。ASPREE-XT数据量大、质量高，将使这项研究成为一项特别重要的研究。 这些财团的重要（通常是主导）组成部分。然而，ASPREE-XT中的现有资源， 在这些合作企业中发挥领导作用是有限的。鉴于ASPREE-XT的重要性 贡献，它需要ASPREE-XT研究人员在这些联盟中发挥领导作用-包括在 分析联盟数据和主要出版物。事实证明，做出这种贡献越来越复杂 鉴于每个集团为参加工作组会议所需的持续努力， 在这份行政补充中，我们要求补充 资助，使ASPREE-XT研究人员充分参与这些基因组学联盟，重点是 与阿尔茨海默氏痴呆症有关，并有助于科学产出。这将提高曝光率和形象 ASPREE-XT研究，并提升ASPREE-XT研究项目的整体影响力和重要性， 特别是在痴呆症和阿尔茨海默病遗传学领域， ASPREE-XT做出有意义的贡献。财团的机会大多是最近才出现的 （在过去6-12个月内），强调需要在基因组学这一研究领域建立新的能力， 及时利用这些新机会。

PROJECT SUMMARY / ABSTRACT Genomics has become an increasingly important aspect of large clinical trials and cohort studies. Genomic data is an essential component for investigating of the joint contribution of environmental and inherited factors on health and disease during ageing. However, the value of genomic information can rarely be achieved by the analysis of data from a single cohort. Rather, data from multiple cohorts must be combined together into a consortium, to achieve statistical power required for novel gene discovery. Many of prominent genomics consortia involve contribution of genomic data from many different NIH-funded cohorts, for genome-wide association studies (GWAS) and meta-analyses. Examples include the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, the Alzheimer's Disease Genetics Consortium (ADGC), and the Alzheimer's Disease Sequencing Project (ADSP). Our study, the ASPirin in Reducing Events in the Elderly (ASPREE) trial - and subsequent observational extension study (ASPREE-XT) - have been fortunate to have collected biospecimens via the ASPREE Healthy Ageing Biobank and generated genomic data on a majority of participants (~15,000 healthy older individuals with targeted sequencing and genome-wide SNP data). This information is of now significant value to in the work of our U19 AG062682 in determining the relative and joint impact of lifestyle, genomics and environmental influences on health in an older population. The availability of the genomic datasets also has presented recent opportunities and imperatives for ASPREE-XT to enter genomics consortia, to contribute to gene discovery efforts. The large size and high quality of ASPREE-XT data will make the study a particularly important (& often dominant) component of these consortia. Yet the current resources within ASPREE-XT to participate in a leadership role in these collaborative ventures is limited. Given the significance of the ASPREE-XT contribution, it requires ASPREE-XT investigators taking leadership roles in these consortia – including in the analysis of consortia data and leading publications. Making this type of contribution is proving increasingly complex and time consuming, given the ongoing efforts required in each consortium to attend working groups, contribute intellectually, participate in analyses, papers etc. In this administrative supplement, we are requesting supplemental funding to enable ASPREE-XT investigators to participate fully in these genomics consortia, with a focus on those related to Alzheimer's Dementia, and contribute to scientific outputs. This would improve the exposure and profile of the ASPREE-XT study, and elevate the overall impact and prominence of the ASPREE-XT research program, especially in the area of dementia and Alzheimer's disease genetics, where considerable opportunities exist for ASPREE-XT to make meaningful contributions. The consortia opportunities have mostly emerged only recently (within the past 6-12 months), highlighting the need to build new capacity in this area of genomics for the study, to capitalize on these new opportunities in a timely fashion.