Vrieze et al. (2013) conducted risk profile scoring in the MCTFR sample using a subsampling approach termed k-fold cross-validation (Breiman and Spector, 1992; Hastie et al., 2009). This approach split the sample into 10 equal subsamples, keeping family members within a subsample to control for correlated genotypes and phenotypes. Nine subsamples were combined to generate a set of associations and effect size weights, and the tenth sample was used as the target sample. The procedure was repeated for every combination of the 10 samples with each subsample serving as the discovery sample nine times and as the target sample once. SNPs were filtered based on LD and genetic risk scores were computed in the target set at multiple P-value thresholds. Similar to the results from the other polygenic score analyses discussed here, the authors observed a polygenic effect for AD, such that as the P-value threshold increased, the percent of variance explained also increased; this effect was also seen for the alcohol consumption phenotype.
