A second method developed to investigate the polygenic nature of complex traits is the risk profile scoring method. Similar to the SNP heritability method, risk profile scoring utilizes associations that do not necessarily meet the strict genome-wide significance threshold, with the hypothesis that this set of nominally associated SNPs may be enriched for true positives. Here, these associations are used to predict risk for a disease trait in a “target” sample given results from a “discovery” sample. For this analysis, a GWAS is conducted in the discovery sample, and using a P-value threshold, the results are used to generate a risk profile score for each subject in the target sample. This score is equal to the sum of the count of risk alleles for that subject weighted by their effect sizes in the discovery sample. The score is then typically used in a regression analysis to evaluate its association with the phenotype of interest in the target sample, as well as the proportion of variance explained (e.g., R2). This approach has been used to investigate the polygenicity of complex traits
