TABLE 1.
Schizophrenia expression in 22q11.2DS and its relationship to having a miRNA target gene overlapped by an additional rare CNV.
| Individuals with an additional genome-wide rare genic CNV overlapping a miRNA target gene | Unadjusted analysis | Adjusted analysis a | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Schizophrenia (n = 100) | Non-psychotic (n = 118) | |||||||||||
| n | % | n | % | OR | 95% CI | p | OR | 95% CI | p | |||
| All miRNA target genes (n = 8,464) b | ||||||||||||
| All Rare CNVs c | 69 | 69.0 | 58 | 49.2 | 2.29 | 1.27 | 4.18 | 0.0038 | 2.12 | 1.17 | 3.85 | 0.0138 |
| Gene Set Restriction d | ||||||||||||
| FMRP targets Darnell e | 11 | 11.0 | 4 | 3.4 | 3.50 | 1.00 | 15.59 | 0.0327 | 3.45 | 1.03 | 11.62 | 0.0455 |
| FMRP targets Ascano e | 16 | 16.0 | 8 | 6.8 | 2.61 | 1.00 | 7.39 | 0.0488 | 2.73 | 1.03 | 7.26 | 0.0437 |
| Nervous system development e | 23 | 23.0 | 13 | 11.0 | 2.40 | 1.09 | 5.51 | 0.0271 | 1.85 | 0.84 | 4.10 | 0.1273 |
| Neuro-function union inclusive e | 28 | 28.0 | 18 | 15.3 | 2.15 | 1.06 | 4.47 | 0.0298 | 1.65 | 0.81 | 3.37 | 0.1661 |
| Brain expression high/medium f | 42 | 42.0 | 31 | 26.3 | 2.03 | 1.10 | 3.75 | 0.0151 | 1.84 | 0.99 | 1.22 | 0.0555 |
| Endocrine/exocrine/reproduction g | 20 | 20.0 | 10 | 8.5 | 2.69 | 1.13 | 6.80 | 0.0175 | 2.55 | 1.09 | 1.45 | 0.0311 |
| 22q11.2 deletion models miRNA targets subset (n = 5,672) h | ||||||||||||
| All Rare CNVs c | 58 | 58.0 | 49 | 41.5 | 1.82 | 1.02 | 3.25 | 0.0398 | 1.64 | 0.91 | 2.97 | 0.097 |
CNV, copy number variant; Unadjusted analysis, two-sided Fisher’s exact test; OR, odds ratio; 95% CI, 95% confidence interval of the odds ratio; miRNA, microRNA; FRMP, Fragile X Mental Retardation Protein.
The p-values, ORs, and 95% CIs listed are for the presence of a miRNA target overlapped by a rare CNV in a logistic regression model with the following additional variables: the total rare CNV size per individual, total number of protein coding genes overlapped by a rare CNV per individual, and sex.
miRNA, target genes retrieved from DIANA-TarBase v8, supported by experimental evidence (see Methods for filtering criteria).
Rare CNVs, with <0.1% frequency in control databases and ≥10 kb in length.
Restricting to individuals with a rare CNV overlapping a miRNA target gene that belongs to a gene set.
Among 19 gene sets belonging to Neuro-functional category of gene sets (Supplementary Table S7). The larger Neuro-function union inclusive gene set includes all genes from the Nervous system development gene set (Supplementary Table S9).
Among seven gene sets belonging to BrainSpan category of gene sets (Supplementary Table S7).
Among seven gene sets belonging to mouse organ systems category of gene sets (Supplementary Table S7).
Subset of the 8,464 genes that are targets of miRNAs, that were found to be differentially expressed in experimental models of the 22q11.2 deletion (Figure 3).