Table 1.
Results of the discovery PWAS of depression in which the depression GWAS (N=500,199) summary statistics were integrated with the ROS/MAP human brain proteomic and genetic data (N = 376) using the FUSION pipeline, followed by SMR and HEIDI tests. Together, these analyses identified 19 genes that are consistent with being causal in depression. These genes contribute to depression pathogenesis via their cis-regulated brain protein abundance.
| Gene | Chr | PWAS Z | PWAS p |
PWAS FDR q |
SMR p |
HEIDI p |
Causal gene | |
|---|---|---|---|---|---|---|---|---|
| 1 | B3GALTL* | 13 | −6.16 | 7.4E-10 | 1.1E-06 | 6.1E-06 | 0.13 | consistent |
| 2 | GMPPB* | 3 | 5.22 | 1.8E-07 | 8.9E-05 | 4.9E-06 | 0.28 | consistent |
| 3 | CTNND1 | 11 | −4.82 | 1.5E-06 | 5.3E-04 | 3.7E-03 | 0.69 | consistent |
| 4 | CNNM2* | 10 | −4.72 | 2.3E-06 | 6.8E-04 | 2.2E-04 | 0.21 | consistent |
| 5 | EPHB2* | 1 | −4.54 | 5.8E-06 | 1.4E-03 | 2.3E-03 | 0.40 | consistent |
| 6 | PSMB4 | 1 | 4.33 | 1.5E-05 | 3.0E-03 | 2.7E-05 | 0.27 | consistent |
| 7 | TKT* | 3 | 4.31 | 1.7E-05 | 3.0E-03 | 2.3E-03 | 0.37 | consistent |
| 8 | TMEM33 | 4 | 4.13 | 3.6E-05 | 5.9E-03 | 2.3E-02 | 0.18 | consistent |
| 9 | THUMPD3* | 3 | 4.06 | 5.0E-05 | 7.3E-03 | 7.2E-03 | 0.21 | consistent |
| 10 | FAHD2B* | 2 | −3.91 | 9.4E-05 | 1.1E-02 | 2.1E-03 | 0.32 | consistent |
| 11 | P2RX7 | 12 | −3.84 | 1.2E-04 | 1.4E-02 | 9.1E-05 | 0.06 | consistent |
| 12 | CACNA2D2 | 3 | −3.73 | 1.9E-04 | 2.0E-02 | 1.4E-02 | 0.55 | consistent |
| 13 | CDH13* | 16 | −3.59 | 3.3E-04 | 3.1E-02 | 3.5E-03 | 0.13 | consistent |
| 14 | TRPT1 | 11 | −3.57 | 3.6E-04 | 3.1E-02 | 2.8E-02 | 0.77 | consistent |
| 15 | HIBADH* | 7 | 3.51 | 4.5E-04 | 3.6E-02 | 9.8E-03 | 0.93 | consistent |
| 16 | LMBRD1 | 6 | −3.45 | 5.6E-04 | 4.0E-02 | 1.6E-02 | 0.69 | consistent |
| 17 | SLC25A12* | 2 | 3.43 | 6.0E-04 | 4.1E-02 | 4.2E-03 | 1.00 | consistent |
| 18 | B3GAT3 | 11 | −3.40 | 6.7E-04 | 4.1E-02 | 5.4E-03 | 0.92 | consistent |
| 19 | NEK4* | 3 | 3.40 | 6.7E-04 | 4.1E-02 | 4.2E-03 | 0.11 | consistent |
| 20 | TMEM25 | 11 | −3.48 | 5.0E-04 | 3.8E-02 | 2.8E-03 | NA | possible |
| 21 | RAB27B | 18 | 5.74 | 9.7E-09 | 7.1E-06 | 4.5E-06 | 0.05 | no |
| 22 | TMEM106B | 7 | 4.02 | 5.9E-05 | 7.9E-03 | 5.8E-04 | 0.01 | no |
| 23 | FAM172A | 5 | −3.56 | 3.7E-04 | 3.1E-02 | 1.4E-02 | 0.02 | no |
| 24 | RGS6 | 14 | −3.41 | 6.5E-04 | 4.1E-02 | 1.4E-02 | 0.03 | no |
Asterisk indicates genes whose cis-regulated brain mRNA levels were associated with depression based on a TWAS of depression that integrated the depression GWAS (N=500,199) with brain transcriptomic and genetic data (N=888). Chr: chromosome. SMR: summary data-level Mendelian randomization. HEIDI: Heterogeneity in dependent instrument. NA means missing value since there were not sufficient SNPs to run the HEIDI test.