Chunk #19 — Polygenic Risk Scores: A Bridge Between Population Variation and Individual Differences — PRS Practicalities — STEP 4: Calculate PRS for each individual in your sample.
For each individual in the target sample, multiply the effect size (if ORs, the log-transformed allelic OR) observed in the discovery GWAS by the number of effect alleles for that variant that the individual possesses. In our example (Figure 1), for each polymorphism, this product term represents an individual’s liability to schizophrenia that is attributable to the alleles present at that single variant. These individual allele scores can then be averaged across the genome to form an overall polygenomic liability, or PRS, for each individual. Typically, an investigator creates multiple PRS that represent degrees of type II error/alpha (i.e., varying p-value thresholds) in the discovery GWAS. Therefore, one might aggregate all variants that were significant at p<1.0, p < .50, p < 0.30, p < .10, < 0.05, p < 5 × 10–3, p < 5 × 10–5 and p < 5 × 10–8 in the discovery GWAS, generating a person-specific PRS for schizophrenia at each p-value threshold. To limit multiple testing, one could select a p-value threshold that is most predictive of variability of the GWAS phenotype or related
