Polygenic risk scores have been used to summarize genetic effects among a group of genetic variants that do not individually achieve significance in a large-scale association study. First a meta-analyses on GWA results is conducted on an initial discovery sample, and the markers are ranked by their evidence for association, usually based on their P-values. An independent target sample is then analyzed by constructing a polygenic score consisting of the weighted sum of the associated alleles within each subject. Association between a trait and this score implies a genetic effect of the trait in the discovery sample on the trait in the target sample. The first successful application of a polygenic risk score analyses was in a GWA study to schizophrenia (31). A polygenic risk score based on the GWA for schizophrenia was associated to the risk of bipolar disorder, but not to several non-psychiatric diseases (which suggested disease specificity). The polygenic risk score method is used in several studies, with mixed results. Some studies report positive associations (for example (32–35)) while others did not find evidence that common genetic
