Genotyping, imputation, and quality control within MVP has been previously described18. Briefly, samples were genotyped using a 723,305-SNP Affymetrix Axiom biobank array, customized for MVP. Imputation was performed with minimac375 using data from the 1000 Genomes Project. For post-imputation QC, SNPs with imputation INFO scores of < 0.3 or minor allele frequencies (MAF) below 0.01 were removed from analysis. For the first tranche of data, 22,183 SNPs were selected through linkage disequilibrium (LD) pruning using PLINK24,76, and then Eigensoft77 was used to conduct principal component analysis on 343,286 MVP samples and 2,504 1000 Genomes Project samples78. The reference population groups in the 1000 Genomes samples were used to define EUR (n = 241,541) and AFR (n = 61,796) groups used in these analyses. Similar methods were used in the second data tranche, which contained 108,416 new MVP samples and the same 2,504 1000 Genomes Project samples. In Tranche 2, 80,694 participants were defined as EUR and 20,584 as AFR. In this manuscript, we report results as the meta-analysis of Tranche 1 and 2 data, either for EUR and AFR separately, or as a trans-ancestral meta-analysis.
