To determine the novelty of the 25 potentially causal genes identified from the meta-analysis of the discovery and replication PWAS of depression, we identified the lowest p-values for the SNPs within 1 Mb of each of these 25 genes using the summary statistics from the largest depression GWAS (N=807,553)10. For five genes (RAB27B, P2RX7, B3GALTL, GMPPB, and CTNND1), the lowest p-values were less than 5×10−08, while the remaining 20 genes had SNPs with p-values ranging from 5.4×10−04 to 2.6×10−07 (Supplementary Table 17), implying genes not implicated in depression by GWAS. These findings are consistent with observations from other TWAS studies that found the novel genes to be from regions below genome-wide significant p-values17,33,34. Furthermore, the PWAS findings point to specific brain proteins that likely contribute to the pathogenesis of depression.
