Polygenic scores were generated using PRS-CS [60] on all genotyped individuals of European descent (n = 67,588) in Vanderbilt University Medical Center’s EHR-linked biobank, BioVU. PRS-CS uses a Bayesian framework to model linkage disequilibrium from an external reference set and a continuous shrinkage prior on SNP effect sizes. We used 1000 Genomes Project Phase 3 European sample [46] as the LD reference. Additionally, we used the PRS-CS-auto option, which allows the software to learn the continuous shrinkage prior from the data. Polygenic scores were constructed from PRS-CS-auto adjusted summary statistics containing 811,292 SNPs. All individuals used for polygenic scoring were genotyped on the Illumina Multi-Ethnic Global Array (MEGA). Genotypes were filtered for SNP (95%) and individual (98%) call rates, sex discrepancies, and excessive heterozygosity. For related individuals, one of each pair was randomly removed (pi_hat > 0.2). SNPs showing significant associations with genotyping batch were removed. Genetic ancestry was determined by principal component analysis performed using EIGENSTRAT [61]. Imputation was completed using the Michigan Imputation Server [45] and the Haplotype Reference Consortium [62] as the reference panel. Genotypes were then
