The P+T method refers to the calculation of PRS using informed LD-pruning (also known as LD-clumping) and P-value thresholding. In this study, we use the implementation of the P+T method in the software package PRSice-253 [https://choishingwan.github.io/PRSice] and its default parameter settings. Specifically, for any pair of SNPs that have a physical distance smaller than 250 kb and an R2 greater than 0.1, the less significant SNP is removed. The polygenic score is then calculated as the sum of the remaining, largely independent SNPs with a GWAS association P-value below a threshold PT, weighted by their marginal effect size estimates. We consider PT ∈ {1E−8, 1E−7, 1E−6, 1E−5, 3E−5, 1E−4, 3E−4, 0.001, 0.003, 0.01, 0.03, 0.1, 0.3, 1} in this paper. The PT value that produces the highest prediction accuracy in a validation data set is selected, and the predictive performance is assessed in an independent testing set.
