Fig. 1: Overview of the COWAS framework.
From: Co-expression-wide association studies link genetically regulated interactions with complex traits
a Genes A and B code for proteins A and B, which interact with each other. The transcription, translation, and interaction processes are regulated by eQTLs, pQTLs, and coQTLs, respectively, which may overlap and are collectively denoted as xQTLs. b Proteins A and B may have direct effects on a complex trait (θA and θB, respectively), but they may also impact the trait through their interactions with each other (θco). c The training stage of COWAS involves first building models to impute the genetically regulated expression levels of each protein from pQTL genotypes, and then building a third model to impute their genetically regulated co-expression. d The testing stage of COWAS involves jointly estimating direct and interaction effects on a complex trait of interest using fitted model weights from the training stage, a linkage disequilibrium reference panel, and GWAS summary statistics for the outcome trait.
