Genetics: Chromosome 11 SOX6

[ME/CFS Science Blog]

Even though this region falls just below the significance threshold, the credible set lies entirely inside the SOX6 gene, making it quite likely that this is the relevant one.



The 3D domain only includes C11orf58 as another protein coding gene. The FLAMES algorithm was also quite confident about SOX6 being the relevant gene for this signal.



The other chromatin analyses didn't reveal much.

For the eQTL I tested more than 2000 datasets but only 2 reached PP.H4 and they were only weak signals.


The Phewas showed a couple of genetic studies that share a signal here including overal health rating, brain-white matter MRI and miserableness.

 

[Verity]

I would explain why it has been so hard to find colocalizing eQTL for the DecodeME hits

Would anyone be able to explain in simple terms what this means?

 

[ME/CFS Science Blog]

Would anyone be able to explain in simple terms what this means?

We have a lot of databases that measured DNA (the genetic code) and RNA (a measure of gene expression). So one would think that looking up the DNA variants that are associated with ME/CFS (from DecodeME) in those databases would tell us which genes it influences.

For example, it could be that people who have the ME/CFS mutations at chromosome 11, tend to have increased RNA for SOX6 compared to those without the mutations. That would give us a solid clue that SOX6 is the causal gene for the DecodeME signal.

Unfortunately, it's not always so easy. We often find nothing in these databases, not just for ME/CFS but in other diseases as well. One possible explanation is that these databases didn't measure the gene expression in the right tissue or cell type or that they need to be measured in special circumstances (for example during early development or during an infection).

 

[Verity]

We have a lot of databases that measured DNA (the genetic code) and RNA (a measure of gene expression). So one would think that looking up the DNA variants that are associated with ME/CFS (from DecodeME) in those databases would tell us which genes it influences.

For example, it could be that people who have the ME/CFS mutations at chromosome 11, tend to have increased RNA for SOX6 compared to those without the mutations. That would give us a solid clue that SOX6 is the causal gene for the DecodeME signal.

Unfortunately, it's not always so easy. We often find nothing in these databases, not just for ME/CFS but in other diseases as well. One possible explanation is that these databases didn't measure the gene expression in the right tissue or cell type or that they need to be measured in special circumstances (for example during early development or during an infection).

Thank you. That is unfortunate. There is so much we don’t know.

I have very little grasp of genetics so I am constantly getting confused around here!

 

[ME/CFS Science Blog]

Looks like SOX6 helps to determine dopamine input to the striatum.

deletion of Sox6 affects striatal innervation and dopamine levels.

Source: Disruption of SOX6 is associated with a rapid-onset dopa-responsive movement disorder, delayed development, and dysmorphic features - PubMed

Sox6+ neurons project to the dorsal striatum and show activity correlated with acceleration

Sox6 expression distinguishes dorsally and ventrally biased dopamine neurons in the substantia nigra with distinctive properties and embryonic origins - PubMed

Severe disruptions of the gene come with Parkinson-like movement problems:
Disruption of SOX6 is associated with a rapid-onset dopa-responsive movement disorder, delayed development, and dysmorphic features - PubMed