Factors affecting PRS accuracy. Disease related factors (e.g., heritability, functional annotation, LD structure, and number of informative SNPs) as well as study design aspects (e.g., sample size, p-value threshold for SNP selection, and sampling variability), affect the power and performance of PRS. Depending on the hypothesis tested and the disease characteristics, improved PRS performance is possible via the appropriate sample size, SNP selection threshold and LD control.