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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.

I think we should try to learn everything and discuss everything that has even been published on eMSN cells. For research, perhaps the next step would be to do animal experiments and test whether these eMSN are involved in sickness behavior during acute infection? I also wonder about...

As I understand it, these are the controls already used in DecodeME.

Think GPR52 would fit well with Paolo's finding on eccentric medium spiny neurons (eMSN), as GPR52 is highly expressed in striatal brain regions where eMSNs are mostly found. It seems to be a receptor that modulates the D2 dopamine signaling pathway.

Not sure; will have to read up. I might have been too eager in making a connection here, so don't think it too seriously.

Don't know if there's a connection, but BTN2A1 seems to be relatively highly expressed on eMSN. Perhaps that is the sensor telling the eMSN that something is wrong. https://www.proteinatlas.org/ENSG00000112763-BTN2A1/single+cell

I was also wondering: how did Paolo managed to find this while the DecodeME preprint did not. The MVP databases only adds 3,891 ME/CFS cases with likely many false positives because it used old ICD diagnostic codes for case selection. But the number of controls in that study was massive, like...

I made a separate thread to discuss the eccentric medium spiny neurons (eMSN). These look like a more specific and informative result than synapses, glutamergic neurons, etc. https://www.s4me.info/threads/eccentric-medium-spiny-neuron-emsn.50276/

The tissue results largely pointed to the brain which was also reported by the DecodeME preprint and Ponting in his talk. See figure 3. Still might be interesting to try other cell types though I do not expect a hit there.

Eccentric medium spiny neuron (eMSN) sometimes called eccentric spiny projection neurons (eSPNs) is the cell type that came up in Paolo Maccallini’s genetic analysis for ME/CFS. He used a meta-anaysis of DecodeME and the Million Veteran Program (Neff = 74,219). Using a tool called MAGMA, Paolo...

Possible link between CRH and the eccentric medium spiny neuron Paolo found: CRF release from a unique subpopulation of accumbal neurons constrains action-outcome acquisition in reward learning

There have been so many weird and denigrating names for our disease: chronic fatigue syndrome, post-exertional malaise, sickness behavior, photophobia. If anything it must mean we're on the right track with "eccentric medium spiny neuron (eMSN) in the claustrum"!

These were the 5 hits in the meta-analysis. The one on chromosome 17 for CA10 is not there but we do have a new one on chromosome 19. Paolo provided the GRCh38 location in the supplementary material: topLeadSNP GRCh38 GRCh37 rs2503773 6:98089269:A:G 6:98537145:A:G rs12579722...