Fig. 1: Overview of methods.

A TWAS was initially conducted using both previous GWAS data and GTEx gene expression information to identify differentially expressed genes associated with ACT. From there, replication of the top associations in an independent cohort and a meta-analysis as well as subsequent functional validation were conducted. Gene set enrichment and pathway analyses identified gene lists and pathways overrepresented in the TWAS. Finally, compound and perturbation gene expression signature matching was conducted to identify compounds and perturbations with similar or dissimilar expression profiles to the TWAS genes.