GWAS risk variants are significantly enriched for genetic variants that impact gene expression (eQTLs)24. This motivates the paradigm of transcriptome-wide association studies (TWAS), which evaluate the association between the expression of each gene and a complex trait of interest. Due to the limited availability of very large samples with measured gene expression and trait values, initial TWAS approaches integrated eQTL and GWAS to identify susceptibility genes either via matching the association signals25–27, via mediation analyses28, or via assessing whether the same causal variant impacts both gene expression and trait under a single causal variant model29–31.
