Effect sizes and effect alleles were derived from genome-wide summary statistics from a large GWAS meta-analysis of 162,082 individuals, all of European ancestry (characteristics of discovery GWAS19 in Supplemental Materials). PRS were created for each COGA individual of genetically verified European descent with SNPs meeting increasingly lenient p-value thresholds from the discovery GWAS (from pT <0.0001 to pT <0.50). Details are provided in Supplementary Materials but briefly, for each COGA individual, effect sizes from the discovery GWAS by Pasman et al., were multiplied by the number of effect alleles for each SNP, and then averaged across all SNPs within a certain p-value threshold (e.g,. pT <0.10) (e.g., tuning parameter36) in the discovery GWAS to create one score per individual for that pT. This pT threshold is not reflective of significance of the PRS in a traditional statistical sense (i.e., p < 0.05). Instead, it is predicated on the assumption of a high degree of polygenicity, which has been found to be true for most complex traits37; therefore, SNPs that do not reach stringent genome-wide significance cutoffs (typically p < 5e-8)
