Three genes (EPHB2, TKT, and NEK4) were identified by the discovery PWAS but their replicability was undetermined due to technical reasons related to the stochastic nature of proteomic sequencing. Nevertheless, they were identified by the TWAS (Table 1, genes with asterisk), and the TWAS results offers a degree of validation. In sum, we have a high level of confidence for the 9 genes that replicated in the replication PWAS and moderate level of confidence for the 3 genes that were associated with depression at both the mRNA- and protein-levels (Table 1 and 2). Together, these 12 genes are likely important in the pathogenesis of depression, acting at the brain protein level, and serving as promising targets for further mechanistic and therapeutic studies.
