In contrast to other gene-based tests, PrediXcan provides the direction of effect, which may yield opportunities for therapeutic development. The development of therapeutics that down-regulate a gene is generally easier to achieve than therapeutics that up-regulate a gene; thus, genes with expression levels that are positively correlated with disease risk may be more favorable drug targets for novel therapies. The direction of effect may also provide information to elucidate pathways and the opportunity to explore systems-based approaches to the development of disease. The prediction models can be applied to genotype data of subjects in large biobanks to investigate potential side-effects of drugs with specific gene targets. Finally, direction of effect can be used to improve the interpretation of sequence analyses of genes showing significant correlation of predicted expression with phenotype, since phenotypes associated with reduced expression of genes are more likely to show a relative excess of rare variants. Indeed, we believe that PrediXcan offers intriguing opportunities to combine results of rare and common variant association tests within whole genome sequencing studies, and more generally, to combine results of rare
