To gain insights into which particular genes in enriched brain tissues were contributing to PTSD, we conducted a combination of a transcriptome-wide association study (TWAS)35 and summary based Mendelian randomization (SMR) analyses36 using GTEx brain tissue data based on the EA GWAS summary data. TWAS identified 25 genes within 9 loci with Bonferroni-significantly different genetically regulated expression levels between PTSD cases and controls (P < 0.05/14,935 unique genes tested) (Fig. 3a, Supplementary Fig. 8, and Supplementary Table 16). SMR identified 26 genes within 4 loci whose expression levels were putatively causally associated with PTSD (P < 0.05/9,003 unique genes tested) (Fig. 3b and Supplementary Table 17). Many of these genes have been previously implicated in PTSD37 and other psychiatric disorders (e.g., CACNA1E, CRHR1, FOXP2, MAPT, WNT3). Notably, the 3p21.31 (including RBM6, RNF123, MST1R, GMPPB, INKA1), 6p22.1 (including ZCAN9 and HCG17) and 17q21.31 (including ARHGAP27, ARL17A, CRHR1, MAPT, FAM215B, LRRC37A2, PLEKHM1, and SPPL2C) regions contained >10 putative causal genes each.
