Table 1.
Disease risk assessment of DISC1-TR downstream candidate genes in genome wide analysis. Gene-based scoring analysis of the downstream candidate genes of DISC1-TR. Residual Variation Intolerance Score (RVIS) is a gene-based scoring tool, which systematically quantified the amount of functional mutations in each gene based on NHLBI GO Exome Sequencing Project (ESP) 6500 and established a genome-wide scoring system to prioritize genes based on their intolerance to standing functional mutations in the human population. The RVIS score is color-coded (red to dark grey, ranging from −4 to 4). The intolerance of functional mutation is positively correlated with the RVIS score. The genes that we did the transcriptional screen with were ranked by RVIS score in three gene collections: DISC1-Interacting (154 genes); HuGE-SZ (1499 genes); Polygenic-SZ (1796 genes). Within each collection, the relative RVIS score is color-coded (orange to white, ranging from the highest to the lowest RVIS score in the collection). %set is the percentile rank of each gene in each collection.
| Gene in fly | Gene in human | RVIS (EA_0.1%) | DISC1-Interacting (n = 154) | HuGE-SZ (n = 1499) | Polygenic-SZ (n = 1796) | ||||
|---|---|---|---|---|---|---|---|---|---|
| Score | % | Rank | % Set | Rank | % Set | Rank | % Set | ||
| Trio | TRIO | −3.68 | 0.2 | 1 | 0.6 | NA | NA | 16 | 0.9 |
| Shot | MACF1 | −3.29 | 0.3 | 2 | 1.3 | 12 | 0.8 | 30 | 1.7 |
| Trio | KALRN | −2.76 | 0.6 | 4 | 2.6 | 24 | 1.6 | 63 | 3.5 |
| beta-spec | SPTBN1 | −2.5 | 0.9 | 8 | 5.2 | NA | NA | 89 | 5.0 |
| Shot | DST | −1.51 | 3.4 | 21 | 13.6 | 107 | 7.1 | 239 | 13.3 |
| Dys/dystrophin | DMD | −1.39 | 4.2 | 23 | 14.9 | 127 | 8.5 | 281 | 15.6 |
| msn/misshapen | TNIK | −1.27 | 5.4 | 26 | 16.9 | 152 | 10.1 | 333 | 18.5 |
| CDC5L | CDC5L | −1.23 | 5.8 | 27 | 17.5 | NA | NA | NA | NA |
| Dys/dystrophin | UTRN | −1.19 | 6.2 | 28 | 18.2 | 166 | 11.1 | 357 | 19.9 |
| Gl/Glued | DCTN1 | −0.75 | 13.9 | 39 | 25.3 | NA | NA | 589 | 32.8 |
| Actin | ACTB | −0.52 | 22.0 | NA | NA | NA | NA | 764 | 42.5 |
| PpD3 | PPP5C | −0.48 | 24.0 | 54 | 35.1 | NA | NA | NA | NA |
| syx1A | STX1A | −0.46 | 25.0 | NA | NA | 504 | 33.6 | 819 | 45.6 |
| SMC2 | SMC2 | −0.4 | 27.3 | NA | NA | NA | NA | NA | NA |
| Krasviazs/Kra | BZW1 | −0.16 | 43.8 | NA | NA | NA | NA | NA | NA |
| snapin-I | SNAPIN | −0.02 | 53.6 | NA | NA | NA | NA | NA | NA |
| snapin-II | SNAPIN | −0.02 | 53.6 | NA | NA | NA | NA | NA | NA |
| snap | NAPA | −0.01 | 54.5 | NA | NA | NA | NA | 1245 | 69.3 |
| c14orf166 | C14orf166 | 0.06 | 58.8 | 91 | 59.1 | NA | NA | NA | NA |
| Syntaxin18 | STX18 | 0.07 | 59.3 | 92 | 59.7 | NA | NA | NA | NA |
| 14-3-3zeta | YWHAZ | 0.08 | 60.1 | 93 | 60.4 | 919 | 61.3 | 1318 | 73.4 |
| blos2, PED4 | BLOC1S2 | 0.22 | 68.2 | NA | NA | NA | NA | NA | NA |
| ref. | −4 | 0.0 | 1 | 0.0 | 1 | 0.0 | 1 | 0.0 | |
| 4 | 100.0 | 154 | 100.0 | 1499 | 100.0 | 1796 | 100.0 | ||