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TPRM3 was mentioned in AstraZeneca's analysis of rare variants in the UK Biobank, although the p-value was 10^-4. AstraZeneca PheWAS Portal This was for the category "Ever had chronic Fatigue Syndrome or Myalgic Encephalomyelitis (M.E.)" which also highlighted BTNA21

I'm somewhat less confident about the genes selected for ME/CFS because of PrecisionLife's approach, and because Snyder's study had only around 200 participants and focused on rare mutations. Would it be an option to use a smaller selection of genes where we have some higher confidence? For...

Tried to make an overview of the geographical distribution of eMSN. Found no sources on this so I counted up the cells per dissection from the Siletti et al. 2023 human brain atlas, mentioned here: https://cellxgene.cziscience.com/e/e6b2ce27-681b-4409-a053-2681875936e5.cxg/ They had data on...

We probably discussed this already but in DecodeME there wasn't a strong signal around TPRM3 (although a weak one at 9:71403764. P Value: 2.29 x 10^-3).

The plot above used p-values but these are also influenced by the size of the GWAS, so would like to use one that uses a standardized effect size that takes sample size and trait heritability into account. There's a 'BETA_STD' in the columns which I suspect might be what I'm looking for but...

I've combined the MAGMA analysis that Duncan et al. 2025 did for other diseases and the analysis @tralfamadorian97 did for ME/CFS using the 461 cell type cluster in the human brain analysis. I've coloured the signals for eMSN (clusters 222-234 and cluster 426) in red. eMSN are involved in many...

So perhaps one way to picture this is to make the analogy to immune disorders where the evidence can suggest a particular cell type (e.g. B-cells) are important. In most immune disorders multiple immune cell types (B, T, NK, neutrophils, dendritic, mast cells, etc.) play a role but there is...

Here's more data from that Yao 2025 paper which Paolo also references in his paper. It look at the 31 superclusters from the Siletti 2023 brain atlas, so a higher level than the 461 clusters trafalmadorian97 looked at or the 2082 that Paolo used. It shows that the eMSN supercluster had a...

Supplementary figure from Yao et al. 2025. showing the overalp betweem eMSN and the other 30 cell type clusters in the human brain atlas. MSN and amygdala excitory show the highest overalp with a Jaccard index of 0.37 and 0.22 respectively. Legend: Figure S6. Jaccard index heatmap. For all...

Ponting statement was only about the 8 significant hits but if you look broader there are some similarities (noted here on several S4ME threads). Genetic evidence suggests they are all diseases of neural communication in the brain.

It was also tested but showed a completely different profile, pointing to B and T cells, rather than neurons. See the graph below. Same with Alzheimer's, which points to microglia. Genetic evidence suggests ME/CFS is more like schizophrenia, autism, epilepsy, fibromyalgia, and...

Would be interested in seeing this for anxiety, depression, and fibromyalgia if eMSN also pops up. If the GWAS summary data is publicly available, it should be possible to do this ourselves?

See that the Duncan et al. 2024 paper "Mappingthe cellular etiology of schizophrenia and complex brain phenotypes" shows that 'sleep duration' had multiple hits for eMSN. Mapping the cellular etiology of schizophrenia and complex brain phenotypes | Nature Neuroscience

PCDH17 PCDH17 Gene - GeneCards | PCD17 Protein | PCD17 Antibody A bit speculative this one because the hit (13:58,456,743 T/C) only reached the 10^-6 threshold in DecodeME, and the gene is quite far off. But PCDH17 "plays a pivotal role in synaptic development and neural circuit refinement. It...

Cluster 136, mostly in the amygdala has only 152 cells compared to, for example 20.000 for cluster 133, so perhaps that makes it less reliable and more likely to be a fluke? Cluster 133 has the following dissections: V1C:62.92%, V2:17.60%, Pro:14.65%, M1C:2.37%, A1C:1.23%, Ig:0.32%...

Wow, thanks. Much appreciated! I noticed that cluster 133 (the yellow dot just below the significance threshold) is also upper-layer intratelencephalic neurons located in the cortex. I do wonder what distinguishes cluster 136 and 133 of IT cells from other ITs that don't come near the...

Thanks, so that might point to the same Intratelencephalic (IT) glutamergic neurons as mentioned above but using another database (of the motor cortex only).

Thanks, guess I was trying to read too much into it, namely whether it really points to eMSN or a particular process or group of genes on them. Cerebellum Regarding that other cell type, these are glutamergic neurons from the Seeker 2023 white matter database, so a bit of an unusual category...

Another clarification: Paolo's readme file says that these are "IDs of overlapping genes". So likely these are only the genes that overlap with the HEAL2 replication.

Am afraid this interpretation of the conditional plot on signal depth across the genome is not correct, because Paolo's supplementary material S5 lists only a couple of genes per cell type tested. These are likely the 'specifically expressed genes (SEGs)' discussed in section 2.6.3. So that...