Aim 2 (common variation) concerns the analysis of genetic risk scores (GRS). For a complex disease or trait, GRS is a single, normally distributed variable that captures the cumulative effect of risk alleles inherited by an individual (e.g., for schizophrenia, bipolar disorder, or body mass index). Computing a GRS requires a training set (i.e., GWAS results) and genome-wide genotypes on independent test subjects (e.g., a population cohort or participants in a clinical trial). The PGC has made training sets publicly available for multiple disorders. This allows researchers to compute GRS for whatever use they deem appropriate. GRS are not yet sufficiently discriminating to be useful clinically (19) but are among the first demonstrably valid biomarkers for psychiatric disorders. GRS derived from PGC results have been widely used in psychiatric research for generating patient strata, exploring diagnostic boundaries, identifying cognitive and behavioral correlates of genetic risk that predate clinical disorders, and evaluating the validity of putative cognitive or imaging phenotypes (47). Many social scientists have embraced the approach, seeing opportunities to study how genetic factors interact with the social environment (e.g., socio-economic status) to influence health and broader outcomes (48).
