How might PRS be improved? In addition to generating larger, well-phenotyped GWAS, and adopting refined approaches for PRS calculation, one potential immediate future pathway is to leverage additional data to enhance and refine meaningful signals. An example of how additional GWAS data may be leveraged in the context of GWAS-based summary statistics to inform PRS construction comes from our multisite study lead by Arloth and Binder (Arloth et al., 2015). Here, the GR agonist dexamethasone was administered to healthy and depressed participants who were genotyped. RNA expression was measured before and after (+3 h) dexamethasone administration. First, we identified SNPs that were associated with dexamethasone-related changes in gene expression. Second, we found that these SNPs were significantly enriched for nominal associations in GWAS of various psychiatric disorders, including depression. Third, we created a PRS of SNPs that are associated with both dexamethasone-induced gene expression and depression and found in independent samples that this profile was predictive of depression as well as an overgeneralized amygdala response. Thus, it is possible to use GWAS derived summary statistics alongside additional targeted results to
