Inclusion of sub-group of ASPREE samples into the ADSP

将 ASPREE 样本子组纳入 ADSP

• 批准号: 10298048
• 负责人: MICHAEL L CUCCARO
• 金额: $ 109.25万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10298048
• 关键词: Age-Years; Alzheimer' s Disease; Amyloid beta-42; Aspirin; Australia; Bioinformatics; Biological Markers; Clinical Data; Clinical Research; Cognitive; DNA; Data; Data Element; Data Set; Diagnosis; Dose; Elderly; Enrollment; Event; Follow-Up Studies; Funding; General Hospitals; Genomics; Genotype; Homozygote; Individual; Institutes; Joints; Light; Massachusetts; Methods; Nerve Degeneration; Not Hispanic or Latino; Outcomes Research; Participant; Phenotype; Plasma; Prevention; Process; Request for Proposals; Sampling; Speed; Subgroup; System; Testing; United States National Institutes of Health; Universities; adjudicate; apolipoprotein E-3; apolipoprotein E-4; clinically relevant; endophenotype; follow-up; genome sequencing; high risk; human genomics; interest; medical schools; neurofilament; programs; protective allele; protective factors; randomized placebo controlled trial; tau Proteins; whole genome

PROJECT SUMMARY The ASPREE (ASPirin in Reducing Events in the Elderly) study was a NIH funded, randomized placebo- controlled trial of daily low-dose aspirin in 19,114 healthy older individuals, completed in 2018 with longitudinal data. ASPREE recently joined the Alzheimer Disease Sequencing Project (ADSP) and transferred whole genome sequencing (WGS) data on 2,796 Non-Hispanic White (NHW) samples to the Genomics Center for Alzheimer Disease (GCAD) to be entered into the ADSP pipeline and incorporated into the Follow-up study of the ADSP (FUS). This supplement requests funds to process these 2,796 samples through GCAD. In addition, 926 high-risk, older unaffected individuals (these include 115 unaffected ApoE4/4 homozygotes >75 years, 609 unaffected ApoE3/4 carriers >85 years of age, and 202 unaffected individuals >90 years of age) have been collected as part of the ASPREE study. Of these 926 high-risk individuals, 502 have had WGS performed, and thus 424 require WGS. All high-risk individuals have been followed longitudinally and have two plasma samples collected at the participants entry and three years into the study. These individuals are of great interest as they have the potential to carry protective variants for AD. This proposal requests funds to perform WGS and plasma biomarker studies on these individuals and be incorporated into the ADSP-FUS dataset. The ASPREE program is bi-national and led in Australia by Monash University (PI McNeil), and in the US by the Berman Center for Outcomes and Clinical Research (PI Murray) and Massachusetts General Hospital/Harvard Medical School (PI Chan). Primary contact for this supplement proposal will be Dr. Paul Lacaze at Monash University, Melbourne, Australia. Specific aim 1 is adjudicate and harmonize clinical data from the two ASPREE datasets to generate high quality inferentially equivalent phenotypes and endophenotypes; Aim 2 is to conduct whole-genome sequencing of 424 high-risk, unaffected samples with longitudinal data ; Aim 3 is to perform biomarker studies on two separate plasma samples (at enrollment and at 3 year follow-up) on all 926 high-risk ASPREE samples; aim 4 is to collaborate with NIAGADS, GCAD and the Penn Neurodegeneration Genomics Center (PNGC and HIHG CGESG QC Teams in processing, storage, and delivery of final datasets to NIAGADS for public data release and aim 5 is to harmonize clinical data from newly acquired and existing FUS datasets to generate high quality inferentially equivalent phenotypes and endophenotypes.

项目概要 ASPREE（ASPirin 减少老年人事件）研究是 NIH 资助的一项随机安慰剂研究。 对 19,114 名健康老年人进行每日低剂量阿司匹林的对照试验，于 2018 年完成，纵向研究 数据。 ASPREE最近加入了阿尔茨海默病测序项目（ADSP）并转让了整个项目 将 2,796 个非西班牙裔白人 (NHW) 样本的基因组测序 (WGS) 数据发送给基因组中心 阿尔茨海默病（GCAD）将进入ADSP管道并纳入后续研究 ADSP（FUS）。本补充要求资金通过 GCAD 处理这 2,796 个样本。此外， 926 名高风险、老年未受影响个体（其中包括 115 名未受影响的 ApoE4/4 纯合子 >75 岁，609 未受影响的 ApoE3/4 携带者 > 85 岁，以及 202 名未受影响的 > 90 岁个体） 作为 ASPREE 研究的一部分收集。在这 926 名高危人群中，有 502 人进行了全基因组测序，并且 因此 424 需要 WGS。所有高危个体均经过纵向随访并采集了两份血浆样本 在参与者进入和研究三年后收集。这些人引起了极大的兴趣，因为他们 有可能携带 AD 的保护性变体。该提案要求提供资金来进行全基因组测序和血浆 对这些个体进行生物标志物研究并纳入 ADSP-FUS 数据集。 ASPREE 项目是两国合作的项目，由澳大利亚莫纳什大学 (PI McNeil) 领导， 美国伯曼结果和临床研究中心 (PI Murray) 和马萨诸塞州综合医院 医院/哈佛医学院（PI Chan）。此补充提案的主要联系人是 Paul Lacaze 博士 澳大利亚墨尔本莫纳什大学。具体目标 1 是裁决和协调来自各研究机构的临床数据 两个 ASPREE 数据集，用于生成高质量的推断等效表型和内表型；目标2 是对424个高风险、未受影响的样本进行全基因组测序，并提供纵向数据；目标 3 是 对所有 926 名患者的两个独立血浆样本（入组时和 3 年随访时）进行生物标志物研究 高风险 ASPREE 样本；目标 4 是与 NIAGADS、GCAD 和宾夕法尼亚州神经退行性疾病中心合作 基因组中心（PNGC 和 HIHG CGESG QC 团队处理、存储和交付最终数据集 NIAGADS 用于公开数据发布，目标 5 是协调新获得的和现有 FUS 的临床数据 数据集来生成高质量的推断等效表型和内表型。