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A curious one is RP11-147C23.1 at location 1:97037083 I think it refers to long non-coding RNAs but it also came up in the fibromyalgia GWAS so that probably isn't a coincidence.

I don't know but in terms of GWAS, DecodeME is still relatively small. It only got 6 significant hits in the primary analysis. Many other diseases have more than 100. So in a way, we're just scratching the surface.

Thanks, seems to confirm what we were already thinking. With the additional tissue enrichment in the brain, cell types pointing to eMSN, and functional gene categories, I think we now have strong evidence that DecodeME points to neural communication as key to the pathology of ME/CFS. This...

In the SNP2GENE you can set the p-value threshold lower so that FLAMES will try to predict more genes for loci that didn't reach the 10^-8 threshold. I've tried it using the lower 5*10^-6 threshold to get a higher number of potential genes. It resulted in 56 independent regions with a hit. I've...

Here are the FLAMES result I got (FLAMES_scores.raw) but put into an excel file with the chromosome positions added to it.

Yes I used 1000G Phase3 EUR, yours might have been a better choice. Not sure if that explains the difference though because it's strange that you only got 5 hits. Couldn't it be due to the sample size given? My interpretation is that they want the total number of individuals in the GWAS as...

Yes probably but it could still be interesting. Made a comparison to immune cells, which is how I currently try to understand it. https://www.s4me.info/threads/eccentric-medium-spiny-neuron-emsn.50276/post-694999

Here's what I got. Looks like it only does the 6 hits that reached significance for the main DecodeME analysis Which are these: And for the first two it could not make a prediction, too many competitors. For the other 4 he gave the following answers. MMS22L for position 6:98432302:C:CA is new.

Looks like the FUMA website has been updated and now has a portal to do FLAMES. https://fuma.ctglab.nl/flames I've tried to give the correct input, but it would be great if others with more skills could try it out as well. For the sample size they require, I gave the total DecodeME sample...

Yeah, although I would be more interested in the results for the fibromyalgia GWAS if its data is publicly available. The genetic architecture of fibromyalgia across 2.5 million individuals - PubMed For the graph I posted, these analyses for eMSN were already done by Duncan et al. They...

Here it says: The Body Trapped in a State of Chronic Infection: RSU Studies a Long-Misunderstood Disease | researchlatvia

It mentions limitations, but none that you already acknowledge in your paper and none that make the results unreliable. The comment itself looks AI-generated to me. As if someone who doesn't understand the methodology asked to find criticism or limitations of the study. Why would anyone write...

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...