Tissue and cell-type enrichments revealed involvement of cerebellum, in addition to other traditionally PTSD-associated brain regions, and interneurons in PTSD risk. Structural alterations in the cerebellum are associated with PTSD66, and large postmortem transcriptomic studies of PTSD consistently reveal differential expression of interneuron markers in prefrontal cortical tissue and amygdala nuclei67–69. We used a combination of TWAS and SMR to probe the causal genes operating within the enriched tissues and cell types with brain transcriptomic data. The identified signals were concentrated in some GWAS loci like 17q21.31 whose inversion region is associated with a range of psychiatric phenotypes and linked to changes in brain structure and function. KANSL1, ARL17B, LINC02210-CRHR1 (encoding a fusion protein with CRHR1) and LRRC37A2 were the top causal genes in both neuronal and non-neuronal cell-types. KANSL1 plays a critical role in brain development. Furthermore, the first single cell transcriptomic study of PTSD confirmed neuronal, excitatory and inhibitory, alterations in 17q21.31 with top alterations in ARL17B, LINC02210-CRHR1 and LRRC37A2, while also emphasizing the involvement of immune and glucocorticoid response in neurons70.
