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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