Large-Scale Genetic Analysis of European Ancestry

DNA from 37,412 blood samples was genotyped on customized Illumina Infinium CoreExome-24 bead arrays and subjected to various quality control filters that resulted in a set of 392,323 polymorphic variants. Principal components and ancestry were estimated by projecting all genotyped samples into the space of the principal components of the Human Genome Diversity Project reference panel using PLINK (938 unrelated individuals) [21 (link), 22 (link)]. Pairwise kinship was assessed with the software KING [23 (link)], and the software fastindep was used to reduce the data to a maximal subset that contained no pairs of individuals with 3rd-or closer degree relationship [24 (link)]. We also removed patients not of recent European descent from the analysis, resulting in a final sample of 30,702 unrelated subjects. Additional genotypes were obtained using the Haplotype Reference Consortium panel of the Michigan Imputation Server [25 (link)] and included over 17 million imputed variants with R² ≥0.3 and minor allele frequency (MAF) ≥0.1%. Genotyping, quality control and imputation are described in detail elsewhere [4 (link)]. Table 1 provides some descriptive statistics of the MGI and UK Biobank samples.