VA Cooperative Studies Program, VA Boston Healthcare System, Boston, MA 02130, USA.
VA Cooperative Studies Program, VA Boston Healthcare System, Boston, MA 02130, USA; Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT 84132, USA.
Am J Hum Genet. 2020 Apr 2;106(4):535-548. doi: 10.1016/j.ajhg.2020.03.004.
The Million Veteran Program (MVP), initiated by the Department of Veterans Affairs (VA), aims to collect biosamples with consent from at least one million veterans. Presently, blood samples have been collected from over 800,000 enrolled participants. The size and diversity of the MVP cohort, as well as the availability of extensive VA electronic health records, make it a promising resource for precision medicine. MVP is conducting array-based genotyping to provide a genome-wide scan of the entire cohort, in parallel with whole-genome sequencing, methylation, and other 'omics assays. Here, we present the design and performance of the MVP 1.0 custom Axiom array, which was designed and developed as a single assay to be used across the multi-ethnic MVP cohort. A unified genetic quality-control analysis was developed and conducted on an initial tranche of 485,856 individuals, leading to a high-quality dataset of 459,777 unique individuals. 668,418 genetic markers passed quality control and showed high-quality genotypes not only on common variants but also on rare variants. We confirmed that, with non-European individuals making up nearly 30%, MVP's substantial ancestral diversity surpasses that of other large biobanks. We also demonstrated the quality of the MVP dataset by replicating established genetic associations with height in European Americans and African Americans ancestries. This current dataset has been made available to approved MVP researchers for genome-wide association studies and other downstream analyses. Further data releases will be available for analysis as recruitment at the VA continues and the cohort expands both in size and diversity.
百万退伍军人计划(MVP)由退伍军人事务部(VA)发起,旨在收集至少 100 万名退伍军人的生物样本。目前,已经从 80 多万名登记参与者中采集了血液样本。MVP 队列的规模和多样性,以及丰富的 VA 电子健康记录,使其成为精准医学的有前途的资源。MVP 正在进行基于阵列的基因分型,为整个队列提供全基因组扫描,同时进行全基因组测序、甲基化和其他“组学”检测。在这里,我们介绍 MVP 1.0 定制 Axiom 阵列的设计和性能,该阵列是作为一个单一的检测方案设计和开发的,用于多民族 MVP 队列。我们开发并对最初的 485856 个人进行了统一的遗传质量控制分析,得到了一个由 459777 个独特个体组成的高质量数据集。668418 个遗传标记通过了质量控制,不仅在常见变体上,而且在罕见变体上显示出高质量的基因型。我们证实,MVP 的大量祖先多样性,非欧洲个体占近 30%,超过了其他大型生物库。我们还通过在欧洲裔美国人和非洲裔美国人血统中复制已建立的与身高相关的遗传关联,证明了 MVP 数据集的质量。目前,这个数据集已经提供给 MVP 的批准研究人员,用于全基因组关联研究和其他下游分析。随着 VA 的招募继续进行,队列在规模和多样性上都在扩大,将有更多的数据发布供分析使用。