PRS analyses were performed using PRSice-2 46. EA summary statistics for the primary phenotype, DSM-IV AD, were used to score individuals in SAGE-EA and OZALC-EA datasets. Due to their well-known roles in AD, the alcohol dehydrogenase (ADH) gene cluster on chromosome 4 (99,985,095bp to 100,430,930bp) and ALDH2 on chromosome 12 (112,196,532bp to 112,276,464bp) were excluded from PRS analyses to allow for estimation of polygenicity attributable to loci with smaller effects. A set of unrelated individuals was randomly selected from each replication sample (SAGE-EA: N=1,373; OZALC-EA: N=1,441) as required by PRSice-2. Variants located within 500kb of the index variant and having r2 ≥0.25 with the index variant were clumped. PRS were derived by multiplying effect sizes from the EA GWAS of the primary phenotype, DSM-IV AD, with the number of effect alleles in each individual in the target dataset. These product terms were then averaged across the total number of included variants. We only used the p-value threshold of p ≤0.05 (i.e., SNPs associated with DSM-IV AD in the discovery EA GWAS at p ≤ 0.05) in order to reduce the burden of multiple testing and included the same covariates as those used in replication analyses in each dataset.
