This lets me find out which brain regions show specific expression for a given set of genes when compared to the rest of the genome and brain.
I dropped in the genes from "Low early-life social class leaves a biological residue manifested by decreased glucocorticoid and increased proinflammatory signaling" by Greg Miller and colleagues. I combined the over and under expressed lists to see where they are turned on across 416 brain regions (nonparametric, AUC/ROC analysis, 1-6 donors per region). The p-values have been FDR corrected for number of regions.
The area I'd guess at is the hypothalamus and 7 of it's 29 regions are significant with all 7 up regulated. Going deeper it's the paraventricular nucleus and supraoptic nucleus in the anterior region. In the tuberal region the arcuate and lateral subregions have higher expression. The paraventricular nucleus (ranked #1 of 416) and supraoptic nucleus are good to see because they link to oxytocin and vaspressin. Both of those have been linked to maternal related behaviour - and so has early life SES.
Here's the top 12 of the 416 regions:
| Rank | Name | Donors |
Q-value
(FDR corrected p-value)
|
| 1 | Supraoptic Nucleus, Left | 5 | 0.000004 |
| 2 | Supraoptic Nucleus, Right | 2 | 0.000004 |
| 3 | central grey of the pons, Right | 1 | 0.00001 |
| 4 | Substantia Nigra, pars reticulata, Left | 6 | 0.0001 |
| 5 | central grey of the pons, Left | 2 | 0.0003 |
| 6 | arcuate nucleus of medulla, Right | 2 | 0.001 |
| 7 | Globose Nucleus, Right | 2 | 0.001 |
| 8 | Paraventricular Nucleus of the Hypothalamus, Left | 5 | 0.001 |
| 9 | Emboliform Nucleus, Right | 2 | 0.001 |
| 10 | globus pallidus, internal segment, Right | 2 | 0.001 |
| 11 | pontine raphe nucleus, Left | 3 | 0.001 |
| 12 | Paraventricular Nucleus of the Hypothalamus, Right | 1 | 0.002 |
It seems the cerebellar cortex turns down these genes while the cerebellar nuclei (globus, emboliform nucleus) turns them on. I'm not sure how to interpret that, but it might be cell type driven.
Periaqueductal gray/central grey of the pons is also strong. That's nice to see because it contains vasopressin and oxytocin receptors and it's in the CAN/central autonomic network. A few of these overlap with the CAN network but I haven't put a p-value on that.
Again, I just wanted to put this neat little result out there online as it's a distraction that has some value I reckon. If anyone is interested I can use different gene lists, narrow to major brain divisions and try it on fetal data (12-16 post conception weeks).
Update: It seems vasopressin and oxytocin are linked to the immune response (from rat studies). Vasopressin and oxytocin neurons activate when LPS is given, and it seems strong in the supraoptic nucleus.
Update: Dr. Miller noted that I'm using gene expression results from blood so it's pretty indirect (I should've mentioned this). My response is that it's rough, but I'm trying to get a perspective into the brain. There's psychiatric studies where they use blood gene expression for looking at Parkinson's and schizophrenia cases. Also, over 90% of genes are turned on the brain.
Update: I found out the hypothalamus is unique in it's connection with the blood. It lacks a normal blood brain barrier it seems. I will have to look at unrelated studies of blood and see if any list of blood expressed genes will express specifically in the hypothalamus.
