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.

项目摘要 ASPREE（减少老年人中的阿司匹林）研究是一项NIH资助的，随机的安慰剂 - 在19,114位健康的老年人中，每日低剂量阿司匹林的对照试验，于2018年完成 数据。 Aspree最近加入了阿尔茨海默氏病测序项目（ADSP）并转移了整个 2,796个非西班牙裔白（NHW）样品的基因组测序（WGS）数据到基因组学中心 阿尔茨海默氏病（GCAD）将进入ADSP管道，并将其纳入随访研究 ADSP（FUS）。该补充要求资金通过GCAD处理这2796个样本。此外， 926高风险，较老的人（包括115个未受影响的APOE4/4纯合子> 75岁，609 未受影响的APOE3/4载体> 85岁，202个未受影响的人> 90岁） 作为ASPREE研究的一部分收集。在这926个高风险个人中，有502个已经进行了WG，并且 因此424需要WG。所有高风险个体均已纵向遵循，并具有两个血浆样本 在参与者的入境和研究三年内收集。这些人非常感兴趣 有可能携带AD的保护性变体。该建议要求资金执行WGS和等离子体 生物标志物研究这些个体，并将其纳入ADSP-FUS数据集中。 ASPREE计划是双国的，由Monash University（PI McNeil）领导，并在 美国伯曼成果与临床研究中心（PI Murray）和马萨诸塞州一般 医院/哈佛医学院（PI Chan）。该补充提案的主要联系人将是保罗·拉克斯博士 在澳大利亚墨尔本的莫纳什大学。具体目标1是裁决和协调临床数据的 两个ASPREE数据集生成高质量的推断等效表型和内型型；目标2 是对具有纵向数据的424个高风险，未受影响的样品进行全基因组测序；目标3是 对所有926 高风险的Aspree样品； AIM 4是与Niagads，GCAD和Penn NeuroDegeneration合作 基因组学中心（PNGC和HIHG CGESG QC团队在处理，存储和交付最终数据集中 Niagads用于公共数据发布和AIM 5是协调新获得和现有FUS的临床数据 数据集生成高质量的推断等效表型和内表型。