Our method also provides advantages for genetic discovery by leveraging the posterior-probabilities of the extant GWAS and candidate gene literature. Although an enrichment analysis cannot be used to identify specific SNPs or genes that may regulate a trait (similar to a genome-wide polygenic risk approach), a confirmed enrichment signal can indicate that a much more narrow and hypothesis-driven set of genes (e.g., 104 in a set versus 20,000+ in a genome-wide polygenic risk model) is associated with a trait of interest. Indeed, our narrow set may represent half of the previously identified polygenic risk for externalizing (Salvatore et al., 2015). Thus, our approach strengthens both the assessment of the phenotype, in addition to refining and narrowing the genes under study, while also being feasable in samples smaller than tens of thousands of people.
