Measuring genetic variation in the multi-ethnic Million Veteran Program (MVP)
By
Haley Hunter-Zinck,
Yunling Shi,
Man Li,
Bryan R. Gorman,
Sun-Gou Ji,
Ning Sun,
Teresa Webster,
Andrew Liem,
Paul Hsieh,
Poornima Devineni,
Purushotham Karnam,
Lakshmi Radhakrishnan,
Jeanette Schmidt,
Themistocles L Assimes,
Jie Huang,
Cuiping Pan,
Donald Humphries,
Mary Brophy,
Jennifer Moser,
Sumitra Muralidhar,
Grant D. Huang,
Ronald Przygodzki,
John Concato,
John M. Gaziano,
Joel Gelernter,
Christopher J. O’Donnell,
Elizabeth Hauser,
Hongyu Zhao,
Timothy J. O’Leary,
Philip S. Tsao,
Saiju Pyarajan,
on behalf of the VA Million Veteran Program
Posted 07 Jan 2020
bioRxiv DOI: 10.1101/2020.01.06.896613
The Million Veteran Program (MVP), initiated by the Department of Veterans Affairs (VA), aims to collect consented biosamples 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 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 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 the substantial ancestral diversity of MVP with nearly 30% non-European individuals, surpassing 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 data set 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.
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