Million Veteran Program Genotyping Pipeline

Blood samples drawn from consenting MVP participants were shipped to the Central Biorepository in Boston, MA, where DNA was extracted and shipped to two external centers for genotyping on an Affymetrix Axiom Biobank array designed specifically for the MVP. The MVP genomics working group applied standard quality control and genotype calling algorithms to the data in batches using the Affymetrix Power Tools Suite (v1.18). Standard quality control pipelines were used to exclude duplicate samples, samples with more heterozygosity than expected, samples with an excess (>2.5%) of missing genotype calls, and samples with discordance of genetically inferred sex versus self-report. We excluded related individuals (halfway between 2^nd and 3^rd degree relatives or closer) as measured by the KING software^{83 (link)}. Prior to imputation, variants that were poorly called or that deviated from their expected allele frequency based on reference data from the 1000 Genomes Project^{84 (link)} were excluded. After pre-phasing using EAGLE v2^{85 (link)}, genotypes from the 1000 Genomes Project^{84 (link)} phase 3, version 5 reference panel were imputed into Million Veteran Program (MVP) participants via Minimac3 software^{86 (link)}. Principal component analysis was performed using the FlashPCA^{87 (link)}, to generate the top 10 genetic principal components explaining the greatest variability.

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Giri A., Hellwege J.N., Keaton J.M., Park J., Qiu C., Warren H.R., Torstenson E.S., Kovesdy C.P., Sun Y.V., Wilson O.D., Robinson-Cohen C., Roumie C.L., Chung C.P., Birdwell K.A., Damrauer S.M., DuVall S.L., Klarin D., Cho K., Wang Y., Evangelou E., Cabrera C.P., Wain L.V., Shrestha R., Mautz B.S., Akwo E.A., Sargurupremraj M., Debette S., Boehnke M., Scott L.J., Luan J., Jing-Hua Z., Willems S.M., Thériault S., Shah N., Oldmeadow C., Almgren P., Li-Gao R., Verweij N., Boutin T.S., Mangino M., Ntalla I., Feofanova E., Surendran P., Cook J.P., Karthikeyan S., Lahrouchi N., Liu C., Sepúlveda N., Richardson T.G., Kraja A., Amouyel P., Farrall M., Poulter N.R., Laakso M., Zeggini E., Sever P., Scott R.A., Langenberg C., Wareham N.J., Conen D., Alexander Palmer C.N., Attia J., Chasman D.I., Ridker P.M., Melander O., Mook-Kanamori D.O., van der Harst P., Cucca F., Schlessinger D., Hayward C., Spector T.D., Marjo-Riitta J., Hennig B.J., Timpson N.J., Wei-Qi W., Smith J.C., Xu Y., Matheny M.E., Siew E.E., Lindgren C., Karl-Heinz H., Dedoussis G., Denny J.C., Psaty B.M., Howson J.M., Munroe P.B., Newton-Cheh C., Caulfield M.J., Elliott P., Gaziano J.M., Concato J., Wilson P.W., Tsao P.S., Velez Edwards D.R., Susztak K., O’Donnell C.J., Hung A.M, & Edwards T.L. (2018). Trans-ethnic association study of blood pressure determinants in over 750,000 individuals. Nature genetics, 51(1), 51-62.

Publication 2018

Axiom Biobank array Power Tools Suite (v1.18).

Blood Eagle Genetic components Genomes Genotypes Heterozygosity Veteran

Corresponding Organization :

Other organizations : Vanderbilt University Medical Center, VA Tennessee Valley Healthcare System, Vanderbilt University, University of Pennsylvania, Queen Mary University of London, William Harvey Research Institute, Memphis VA Medical Center, Emory University, Philadelphia VA Medical Center, VA Salt Lake City Healthcare System, VA Boston Healthcare System, Imperial College London, University of Leicester, Bordeaux Population Health, Inserm, Université de Bordeaux, University of Michigan–Ann Arbor, University of Cambridge, MRC Epidemiology Unit, McMaster University, University of Dundee, Ninewells Hospital, Hunter Medical Research Institute, Lund University, Leiden University Medical Center, University Medical Center Groningen, University of Groningen, Medical Research Council, University of Edinburgh, MRC Institute of Genetics and Molecular Medicine, King's College London, The University of Texas Health Science Center at Houston, University of Liverpool, Broad Institute, Boston University, London School of Hygiene & Tropical Medicine, University of Bristol, Washington University in St. Louis, Université de Lille, Institut Pasteur de Lille, Centre Hospitalier Universitaire de Lille, Wellcome Centre for Human Genetics, University of Eastern Finland, Wellcome Sanger Institute, Population Health Research Institute, Brigham and Women's Hospital, Harvard University, Institute of Genetic and Biomedical Research, National Institute on Aging, Wellcome Trust, Valley Health System, Oulu University Hospital, Harokopio University of Athens, University of Washington, National Institute for Health Research, Massachusetts General Hospital, VA Connecticut Healthcare System, Atlanta VA Medical Center, Atlanta Medical Center, VA Palo Alto Health Care System

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Variable analysis

independent variables

None explicitly mentioned

dependent variables

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control variables

Duplicate samples were excluded
Samples with more heterozygosity than expected were excluded
Samples with an excess (>2.5%) of missing genotype calls were excluded
Samples with discordance of genetically inferred sex versus self-report were excluded
Related individuals (halfway between 2nd and 3rd degree relatives or closer) were excluded
Variants that were poorly called or deviated from their expected allele frequency based on reference data from the 1000 Genomes Project were excluded
Principal component analysis was performed to generate the top 10 genetic principal components explaining the greatest variability

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