To identify and prioritize putative causal genes, we performed a transcriptome-wide association study (TWAS), imputing the genetically regulated gene expression using EpiXcan50 and models trained on expression data from the PsychENCODE Consortium51,52 for genes and isoforms detected in the dorsolateral prefrontal cortex (DLPFC). Among 34,646 transcripts (genes and isoforms) tested, we identified 2,541 transcripts at FDR<0.05 and, after Bonferroni correction of all transcripts tested, 324 transcripts from 201 genes showed significant differential imputed gene expression (Bonferroni P-value threshold P=1.44x10−10) in DLPFC between depression and control groups (Supplementary Table S9). The Bonferroni significant transcripts were located in 88 independent regions53. The top gene/isoform is labeled in Figure 1D and regional TWAS/GWAS Miami-plots for each of the 88 regions are shown in Supplementary Figure S10, six highlights are shown in Extended Data Figure 1. In 38 of the 88 regions, the top transcript was >100 times more significant than the second-most associated gene/isoform in the region (Supplementary Table S9B), appointing those as plausible causal candidates.
