PrediXcan, by design, exploits genetic control of phenotype through the mechanism of gene regulation as a way to identify trait-associated genes. Figure 1 is a schematic diagram of the regulatory mechanism that is tested with PrediXcan. An individual's gene expression level (typically unobserved in a GWAS) is decomposed into a genetically regulated expression (GReX) component, a component altered by the trait itself (i.e., a reverse causal effect that may occur if disease status or other conditions alter expression levels), and the remaining component attributable to environmental and other factors. PrediXcan tests the mediating effect of gene expression by quantifying the association between GReX and the phenotype of interest.
