Table 3.
Gene set association, previously implicated in schizophrenia
| Gene Set | CNVs >100Kb | CNVs >500Kb | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Name (source) | Genes | Type | CNVs | Genes | OR | 95% CI | Pemp | Adj_P | CNVs | Genes | OR | 95% CI | Pemp | Adj_P |
| mir137 targets (TargetScan) | 1089 | DEL & DUP | 799 | 274 | 1.04 | (0.909, 1.19) | 0.3303 | 1 | 259 | 106 | 1.24 | (0.969, 1.59) | 0.03377 | 1 |
| DEL | 228 | 96 | 1.03 | (0.797, 1.32) | 0.4005 | 1 | 101 | 48 | 1.43 | (0.936, 2.17) | 0.04573 | 1 | ||
| DUP | 571 | 218 | 1.04 | (0.888, 1.22) | 0.382 | 1 | 158 | 72 | 1.13 | (0.819, 1.55) | 0.2149 | 1 | ||
| Calcium signaling (KEGG:hsa04020) | 178 | DEL & DUP | 238 | 45 | 2.48 | (1.36, 4.51) | 0.0004 | 0.041 | 87 | 19 | 4.39 | (1.46, 13.2) | 0.00042 | 0.047 |
| DEL | 55 | 19 | 0.87 | (0.656, 1.16) | 0.856 | 1 | 26 | 8 | 1.18 | (0.73, 1.91) | 0.2473 | 1 | ||
| DUP | 183 | 34 | 1.07 | (0.834, 1.37) | 0.2788 | 1 | 61 | 14 | 1.53 | (0.992, 2.36) | 0.01746 | 1 | ||
| FRMP targets (Darnell et al.) | 810 | DEL & DUP | 913 | 225 | 1.14 | (1.02, 1.27) | 0.0079 | 0.66 | 286 | 86 | 1.27 | (1.07, 1.51) | 9.00E-04 | 0.095 |
| DEL | 209 | 79 | 1.09 | (0.903, 1.33) | 0.1683 | 1 | 89 | 31 | 1.7 | (1.08, 2.67) | 0.00038 | 0.043 | ||
| DUP | 704 | 185 | 1.16 | (1.01, 1.32) | 0.0162 | 1 | 197 | 69 | 1.17 | (0.956, 1.43) | 0.04766 | 13 | ||
| PSD (Kirov et al) | 668 | DEL & DUP | 655 | 161 | 1.13 | (0.982, 1.3) | 0.0358 | 1 | 295 | 64 | 1.4 | (1.12, 1.74) | 0.00062 | 0.067 |
| DEL | 174 | 58 | 1.17 | (0.875, 1.57) | 0.1604 | 1 | 93 | 26 | 1.57 | (1, 2.45) | 0.01749 | 1 | ||
| DUP | 481 | 132 | 1.12 | (0.958, 1.32) | 0.0614 | 1 | 202 | 47 | 1.35 | (1.05, 1.73) | 0.00648 | 0.55 | ||
| PSD/ARC (Kirov et al) | 28 | DEL & DUP | 103 | 5 | 1.12 | (0.757, 1.66) | 0.307 | 1 | 79 | 3 | 1.2 | (0.759, 1.91) | 0.2138 | 1 |
| DEL | 47 | 4 | 1.19 | (0.662, 2.12) | 0.2981 | 1 | 38 | 3 | 1.1 | (0.557, 2.16) | 0.3793 | 1 | ||
| DUP | 56 | 4 | 1.09 | (0.644, 1.86) | 0.4031 | 1 | 41 | 2 | 1.22 | (0.648, 2.29) | 0.2741 | 1 | ||
| PSD/mGluR5 (Kirov et al) | 38 | DEL & DUP | 35 | 11 | 1.7 | (0.854, 3.4) | 0.0485 | 1 | 24 | 3 | 4.59 | (1.56, 13.5) | 0.00022 | 0.025 |
| DEL | 15 | 6 | 1.77 | (0.594, 5.3) | 0.1635 | 1 | 10 | 2 | 16.7 | (0.817, 341) | 5.00E-04 | 0.056 | ||
| DUP | 20 | 7 | 1.61 | (0.658, 3.95) | 0.1009 | 1 | 14 | 2 | 2.62 | (0.817, 8.41) | 0.02174 | 1 | ||
| PSD/NMDAR (Kirov et al) | 61 | DEL & DUP | 52 | 22 | 2.37 | (1.31, 4.29) | 0.0010 | 0.11 | 28 | 11 | 5.8 | (2, 16.8) | 3.00E-05 | 0.0038 |
| DEL | 19 | 9 | 2.04 | (0.763, 5.46) | 0.0774 | 1 | 10 | 5 | 17.27 | (0.849, 351) | 0.00058 | 0.063 | ||
| DUP | 33 | 16 | 2.56 | (1.22, 5.39) | 0.0038 | 0.34 | 18 | 7 | 3.79 | (1.24, 11.6) | 0.00235 | 0.22 | ||
| PSD/PSD-95 (Kirov et al) | 65 | DEL & DUP | 80 | 17 | 1.81 | (1.15, 2.86) | 0.0021 | 0.20 | 23 | 6 | 4 | (1.34, 11.9) | 0.00118 | 0.12 |
| DEL | 35 | 9 | 2.87 | (1.32, 6.22) | 0.0011 | 0.11 | 18 | 5 | 32.18 | (1.71, 604) | 2.00E-05 | 0.0025 | ||
| DUP | 45 | 11 | 1.31 | (0.725, 2.35) | 0.141 | 1 | 5 | 3 | 0.23 | (0.026, 2.1) | 0.9425 | 1 | ||
| GWAS P<0.001 (Ripke et al.) | 2691 | DEL & DUP | 3543 | 819 | 1.04 | (0.981, 1.1) | 0.119 | 1 | 937 | 355 | 1.21 | (1.1, 1.33) | 4.00E-05 | 0.0049 |
| DEL | 1210 | 299 | 1.04 | (0.923, 1.16) | 0.2869 | 1 | 279 | 110 | 1.31 | (1.07, 1.61) | 0.0041 | 0.3649 | ||
| DUP | 2333 | 679 | 1.04 | (0.977, 1.12) | 0.1464 | 1 | 658 | 295 | 1.2 | (1.08, 1.33) | 0.00021 | 0.025 | ||
| Mitochondrion (Kirov et al) | 193 | DEL & DUP | 143 | 52 | 1.14 | (0.844, 1.55) | 0.204 | 1 | 67 | 25 | 1.63 | (1, 2.64) | 0.01944 | 1 |
| DEL | 60 | 21 | 2.12 | (1.22, 3.67) | 0.0015 | 0.15 | 40 | 13 | 4.31 | (1.71, 10.9) | 4.00E-05 | 0.0049 | ||
| DUP | 83 | 42 | 0.79 | (0.528, 1.17) | 0.8908 | 1 | 27 | 17 | 0.61 | (0.289, 1.29) | 0.9201 | 1 | ||
| MitoCarta (Pagliarini et al.) | 892 | DEL & DUP | 756 | 232 | 1.06 | (0.948, 1.19) | 0.1439 | 1 | 229 | 99 | 1.28 | (1.04, 1.56) | 0.00295 | 0.27 |
| DEL | 311 | 86 | 1.18 | (0.98, 1.42) | 0.0277 | 1 | 105 | 39 | 1.74 | (1.12, 2.71) | 0.00019 | 0.022 | ||
| DUP | 445 | 190 | 0.98 | (0.835, 1.15) | 0.6469 | 1 | 124 | 79 | 1.07 | (0.824, 1.38) | 0.3387 | 1 | ||
DEL: deletions. DUP: duplications. All tests were one-sided assuming enrichment in cases using genic CNVs. #CNV = the number of events that overlapped any gene in the geneset by ≥1bp. #genes = the number of unique genes in the geneset that had at least 1 genic CNV hit (≥1bp overlap). OR=odds ratio, indicating the increase in risk for schizophrenia correcting for rate and size of genic CNVs and genotyping batch effect (a continuity correction applied if necessary). CI: confidence interval. Pemp, empirical P values were obtained in PLINK by 100,000 permutations and permuting phenotype labels within genotyping batches. Adj_P: Holm-Bonferroni multiple-testing adjusted P values considering all 126 tests performed in Table 3 and Table S16.