Table 4.
The 40 potential driver genes are prioritized by the CFG method based on AlzData database.
| Gene | AD-related evidence | CFG | |||||
|---|---|---|---|---|---|---|---|
| eQTL | GWAS | PPI | Early_DEG | Pathology cor | |||
| (Aβ) | (Tau) | ||||||
| GJA1 | 2 | 2 | PSEN1, MAPT, APOE | yes | 0.388** | 0.131ns | 5 |
| FOXO1 | 1 | 0 | PSEN2 | yes | 0.270ns | 0.526* | 4 |
| PRKX | 3 | NA | PSEN1 | yes | 0.352* | –0.023ns | 4 |
| RPH3A | 5 | 2 | - | yes | –0.199ns | –0.738** | 4 |
| CASP6 | 5 | 0 | APP, PSEN1, PSEN2, MAPT | yes | 0.482*** | 0.738** | 4 |
| CRMP1 | 1 | 3 | MAPT | NA | –0.304* | –0.506ns | 4 |
| RGS4 | 1 | 32 | - | yes | –0.419** | –0.579* | 4 |
| NPTX2 | 1 | 1 | - | yes | –0.688*** | –0.783*** | 4 |
| RPS27 | 1 | 0 | PSEN2 | yes | 0.503*** | 0.662** | 4 |
| MEGF10 | 3 | 8 | - | yes | 0.559*** | 0.120ns | 4 |
| AP2A1 | 1 | 0 | APP, PSEN2, MAPT | yes | –0.277ns | –0.585* | 4 |
| PITPNC1 | 10 | 1 | - | yes | –0.128ns | –0.638* | 4 |
| AGT | 1 | 0 | APP, PSEN1, APOE | yes | –0.359* | 0.002ns | 4 |
| AQP4 | 7 | 4 | - | yes | 0.800*** | 0.275ns | 4 |
| MYT1L | 3 | 12 | - | yes | –0.488*** | –0.583* | 4 |
| IQGAP1 | 1 | 0 | PSEN1 | yes | 0.310* | 0.282ns | 4 |
| IGFBP7 | 8 | 0 | MAPT, APOE | yes | 0.353* | 0.510ns | 4 |
| CITED2 | 1 | 0 | APP, PSEN1, APOE | yes | –0.433** | –0.772*** | 4 |
| SMAD1 | 16 | 1 | APP, APOE | NA | –0.332* | –0.497ns | 4 |
| CDH7 | 0 | 1 | PSEN1 | yes | –0.345* | –0.691** | 4 |
| MSRB2 | 5 | 2 | - | yes | 0.32* | 0.609* | 4 |
| DBI | 1 | 1 | - | yes | 0.780*** | 0.718** | 4 |
| PELI2 | 2 | 0 | PSEN2 | yes | 0.591*** | –0.107ns | 4 |
| AVEN | 1 | 1 | - | yes | 0.525*** | 0.008ns | 4 |
| F13A1 | 7 | 3 | APP, APOE | NA | 0.195ns | 0.623* | 4 |
| SLA | 1 | 0 | PSEN1, MAPT | yes | 0.114ns | 0.662** | 4 |
| ADAMTS20 | 2 | 17 | - | yes | 0.085ns | 0.587* | 4 |
| RARB | 6 | 2 | PSEN2 | yes | –0.064ns | –0.387ns | 4 |
| SDC2 | 8 | 3 | PSEN1, PSEN2, MAPT, APOE | yes | 0.041ns | 0.086ns | 4 |
| DCN | 8 | 0 | APP, PSEN1, MAPT, APOE | yes | –0.416** | 0.546* | 4 |
| CCR5 | 1 | 0 | APP | yes | 0.769*** | 0.616* | 4 |
| GPRC5B | 2 | 41 | - | yes | 0.307* | –0.248ns | 4 |
| IRF5 | 1 | 0 | APP, PSEN1, PSEN2, MAPT, APOE | yes | 0.879*** | 0.839*** | 4 |
| IGFBP7 | 8 | 0 | MAPT, APOE | yes | 0.353* | 0.510ns | 4 |
| CXCL12 | 1 | 0 | APP, PSEN2, MAPT, APOE | yes | 0.432** | –0.069ns | 4 |
| CREM | 1 | 0 | PSEN1, MAPT, APOE | yes | –0.439** | –0.396ns | 4 |
| EHHADH | 14 | 0 | MAPT, APOE | yes | 0.438** | –0.022ns | 4 |
| SLC1A3 | 7 | 1 | - | yes | 0.651*** | 0.494ns | 4 |
| VAV3 | 0 | 5 | MAPT | yes | 0.319* | –0.284ns | 4 |
| IL15 | 2 | 18 | - | yes | 0.623*** | 0.685** | 4 |
“NA,” not applicable due to missing related data for the target gene. AD, Alzheimer's disease; CFG, convergent functional genomics score based on the total number of lines of AD-related evidence; DEG, differentially expressed gene; eQTL, the total number of risk SNPs based on the IGAP data setthat were able to regulate expression of the target gene; GWAS, the total number of risk SNPs within the target gene based on the IGAP data set; PPI, AD core genes (APP, PSEN1, PSEN2, MAPT, and APOE) that had a significant protein-protein interaction with the target genes; Early_DEG: target gene is differentially expressed in AD mouse models before AD pathology emergence; Expression correlation of the target gene and AD pathology in AD mice was performed for the Aβ line AD mice in Mouse (marked as Aβ) and the Tau line AD mice in Mouse (marked as Tau). *P < 0.05; **P < 0.01; ***P < 0.001.