gTable 2:
Results of the replication PWAS and meta-analysis of the discovery and replication PWAS. A replication PWAS was performed using an independent brain proteomic dataset (n=152) and an independent depression GWAS (N=307,353 23andMe participants; Supplementary Table 4). Focusing on the 19 FDR-significant genes identified by the discovery PWAS and consistent with being causal by SMR, 13 were found in the replication PWAS and a meta-analysis was performed. Replication was declared if the unadjusted meta-analysis p-value was smaller than both the unadjusted discovery and replication PWAS p-values and direction of effect was consistent between the discovery and replication PWAS results. Unadjusted p-values for the discovery, replication, and meta-analysis PWAS results are given. The direction of effect for the discovery and replication interpretation are given. Based on the replication criteria, 9 of the 13 genes (69%) showed evidence for replication.
| Gene | Chr | Discovery PWAS p |
Replication PWAS p |
meta-analysis p-value | Direction | Replicated | |
|---|---|---|---|---|---|---|---|
| 1 | CTNND1 | 11 | 1.5E-06 | 7.5E-04 | 4.1E-09 | −− | yes |
| 2 | CNNM2* | 10 | 2.3E-06 | 1.1E-02 | 1.0E-07 | −− | yes |
| 3 | P2RX7 | 12 | 1.2E-04 | 5.4E-04 | 2.8E-07 | −− | yes |
| 4 | PSMB4 | 1 | 1.5E-05 | 4.8E-02 | 2.9E-06 | ++ | yes |
| 5 | FAHD2B* | 2 | 9.4E-05 | 2.6E-02 | 7.6E-06 | −− | yes |
| 6 | HIBADH* | 7 | 4.5E-04 | 5.4E-02 | 6.8E-05 | ++ | yes |
| 7 | CACNA2D2 | 3 | 1.9E-04 | 1.1E-01 | 6.9E-05 | −− | yes |
| 8 | SLC25A12* | 2 | 6.0E-04 | 4.6E-02 | 7.7E-05 | ++ | yes |
| 9 | CDH13* | 16 | 3.3E-04 | 8.0E-02 | 8.0E-05 | −− | yes |
| 10 | B3GALTL* | 13 | 7.4E-10 | 4.1E-01 | 3.7E-08 | −− | no |
| 11 | GMPPB* | 3 | 1.8E-07 | 7.0E-01 | 7.2E-06 | ++ | no |
| 12 | THUMPD3* | 3 | 5.0E-05 | 9.0E-01 | 7.1E-04 | ++ | no |
| 13 | B3GAT3 | 11 | 6.7E-04 | 6.3E-01 | 1.2E-02 | −+ | no |
Asterisk indicates genes whose cis-regulated brain mRNA levels were associated with depression from a TWAS of depression integrating the depression GWAS (N=500,199) with transcriptomic and genetic data (N=888) using FUSION. Direction refers to the direction of association between the cis-regulated protein level and depression. Replicated refers to whether the gene fulfills criteria for replication, which are an unadjusted meta-analysis p-value smaller than both the unadjusted discovery and replication PWAS p-values and direction of effect was consistent between the discovery and replication PWAS results.