Characteristics of sistematic review and selected studies
Our systematic review revealed 96 publications performed in Homo sapiens, using expression profiling by high throughput sequencing (RNAseq). After evaluation, we selected 6 studies eligible for our analyses: GSE174407, GSE138082, GSE80655, GSE42546, GSE78936 and SRP102816. In turn, GSE138082 and GSE80655 contained data about three different regions, arising a total number of 10 data sets.
Distribution of samples in studies
| Study ID | Brain region | Control | Schizophrenia | Control | Schizophrenia | Total |
|---|---|---|---|---|---|---|
| GSE-174407 | Frontal cortex | 21 | 21 | 8 | 8 | 58 |
| GSE-138082 | Hippocampus, CA1 | 10 | 9 | 3 | 4 | 26 |
| GSE-138082 | Hippocampus, CA3 | 10 | 9 | 3 | 4 | 26 |
| GSE-138082 | Hippocampus, DG | 10 | 9 | 3 | 4 | 26 |
| GSE-80655 | Dorsolateral prefrontal cortex | 21 | 21 | 3 | 3 | 48 |
| GSE-80655 | Anterior cingulate cortex | 21 | 21 | 3 | 3 | 48 |
| GSE-80655 | Nucleus accumbens | 21 | 21 | 3 | 3 | 48 |
| GSE-42546 | Hippocampus, DG | 17 | 9 | 12 | 8 | 46 |
| GSE-78936 | Orbitofrontal cortex | 9 | 11 | 3 | 5 | 28 |
| SRP-102186 | Amygdala | 19 | 19 | 5 | 3 | 46 |
| Total | 159 | 150 | 46 | 45 | 400 |
Gene meta-analysis summary
We performed three meta-analyses based on the brain region studied: prefrontal cortex, hippocampus and whole brain including all data sets available. We used a random effects model (DerSimoniand & Laird) applied on a sex comparison ((Female Schizophrenia - Female Control) - (Male Schizophrenia - Male Control)), henceforth SDID. The summary results are described in the following table:
| Genes | Differentially expressed | Up in males | Up in females | |
|---|---|---|---|---|
| Prefrontal cortex | 27446 | 265 | 221 | 44 |
| Hippocampus | 15365 | 1414 | 649 | 765 |
| All-studies | 29005 | 66 | 41 | 25 |
Functional enrichment summary
After meta-analyses, we performed a gene set expression analysis based on the genes lists. We used the biological process (BP) ontology from Gene Ontology. A summary of the results obtained is shown in the following table:
| Altered BP | Increased in males | Increased in females | |
|---|---|---|---|
| Prefrontal cortex | 1149 | 1085 | 57 |
| Hippocampus | 238 | 20 | 218 |
| All-studies | 44 | 10 | 34 |
Then, we used the gene regulatory network of DoTothEA to analyse alterations in the activity of transcription factors. A summary of the results obtained is shown in the following table:
| Differentially activated | Activated in males | Activated in females | |
|---|---|---|---|
| Prefrontal cortex | 18 | 17 | 1 |
| Hippocampus | 40 | 16 | 24 |
| All-studies | 34 | 15 | 19 |
