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Yes, but it also came up in DecodeME itself https://www.s4me.info/threads/genetics-chromosome-1-rabgap1l.45502/post-693850 It's in the RABGAP1L region, but given what we know now about eMSN , GPR52 might be a more likely candidate. From what I understand, it's a receptor that modulates...

PCDH8, which plays a role in synaptic reorganization and down-regulation of dendritic spines. PCDH8 Gene - GeneCards | PCDH8 Protein | PCDH8 Antibody It's on chromosome 13. We thought that the DecodeME signal there pointed to OLFM4, as it is closer, but the fibromyalgia GWAS also found a signal...

Zooming in on the Saunders et al. 2018 paper that discovered eMSN. Molecular Diversity and Specializations among the Cells of the Adult Mouse Brain - PubMed This was a major study where they built a brain-wide cell atlas of mice by extracting tissue and profiling individual cells' RNA using...

Agree, although I think the evidence suggests these cells are likely to play a key role in ME/CFS pathology.

Some speculation about this: - Perhaps some eMSN are in close enough proximity and well enough connected (e.g. those in the nucleus accumbens) to influence the hypothalamus - Perhaps eMSN CRH has influences through the ventricles - Perhaps there is a middle-man that interprets the excess of CRH...

My guess is that a little bit of CRH stimulates production, a bit like seeing other footballers on the pitch as a sign that the game has started. But that too much CRH gives negative feedback as so often happens in biology, a bit like seeing too many football players on the pitch already, so you...

Thanks! Perhaps this thread would be more suitable for discussing the CRH connection, because it's more of a side issue in the eMSN finding. I was thinking about a hypothesis taking the following steps: - Genetic data suggests that eMSN are the main cell type in ME/CFS pathology - The current...

@tralfamadorian97 is also doing interesting analyses using the DecodeME data, including the MAGMA analysis that links DNA results of ME/CFS patients to gene expression (scRNAseq) data from the Human Brain Atlas. So this is similar to what Paolo did, but with only the DecodeME data (not those...

Thanks, I see this as confirmation that the data really points to eMSN and that it wasn't a fluke or error from the meta-analysis Paolo did.

@jnmaciuch When you have time/energy, would also be interested in your opinion on the brain imaging studies on fatigue during sickness behavior pointing to the left nucleus accumbens and putamen. The ME/CFS genetic data seems to highlight the striatal region with genes such as TSHZ3, GPR52, HTT...

Hmm, think this overstates it a little because there are likely tons of cell types that do not produce CRH as prominently as eMSN. Genetic data suggests that eMSN are the main cell type that is overfiring and they probably have CRH as co-factor. So if this theory is true, there would be too...

Thanks for sharing this. My counterpoint would be that the genetic data is pointing to eMSN cells (all over the body) as key to ME/CFS pathology. The CRH is just an extra bonus that could make the autopsy findings fit. So it doesn't matter that match if other cells can make CRH as well, because...

Impressive @tralfamadorian97 , thanks. Do check out Paolo Maccallini's meta-analysis which found some stronger results than DecodeME alone: https://www.s4me.info/threads/biological-insights-from-genome-wide-association-studies-and-whole-genome-sequencing-of-me-cfs-2026-maccallini-et-al.50225/...

The Human protein atlas gives a list of 114 genes with elevated expression in Eccentric medium spiny neuron compared to other brain cell clusters. Search: sc_brain_region_category_rna:Eccentric medium spiny neuron;Cell type enriched,Group enriched,Cell type enhanced AND sort_by:tissue specific...

Could be that this hit doesn't point to OLFM4 but to PCDH8 which plays a role in synaptic reorganization and down-regulation of dendritic spines. PCDH8 Gene - GeneCards | PCDH8 Protein | PCDH8 Antibody The fibromyalgia GWAS also found a hit near OLFM4 but the FLAMES tool suggested PCDH8 as the...

Question for moderators: Could we make this thread members-only so that AI (mostly Google's gemini) doesn't use read it? It messes up replies when you ask questions about it, strengthening confirmation bias. Thanks in advance,

Had a look at what's already out there, mostly small studies in mice given LPS or people with hepatitis C or malignant melanoma given interferon-alpha. A problem is that sickness behavior includes things like fever, lack of appetite, depression/anhedonia, slowed moving that likely isn't...

Yes this something we haven't discussed much but the fibromyalgia results were very similar to those from DecodeME. Genes such as HTT, OLFM4, GPR52, DCC, PCDH8, came up in the fibromyalgia GWAS as well. Caudate and putamen were included in the significant brain regions while cortical...

Agree, thanks for pointing this out! To give a bit more background: HTT stands for Huntingtin, the gene behind the Huntington disease. HTT is important for axonal transport and helps in regulating the expression of survival factors like BDNF (Brain-Derived Neurotrophic Factor). Medium...

The ones on medium spiny neurons (MSN) might be interesting as well, but it's only the eccentric subgroup that is highlighted by the genetic analysis.