association findings for several ten thousand SNPs from a discovery sample to calculate a summary score for each individual in a target sample. Subsequent analyses are performed to test whether the cases in the target sample have different scores to the controls in the target sample. Therefore, a GWAS is first carried out in a discovery sample. Following this step, the polygenic score for each individual in the target sample is calculated by counting the number of reference alleles (e.g. risk alleles or minor alleles) of this subject on any of the included loci. This number is weighted by multiplication with the log(OR) of the respective marker in the discovery sample. The sum of all of these products is then calculated and divided by the number of included loci. Finally, the association of this score with disease status is tested in the target sample by its inclusion as a predictor in a logistic regression model. The finding of the presence of a polygenic component to AD would indicate that many more individual genetic variants of small effect still await detection.
