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Some caution regarding the 25 CFS patients in this study: They also note the following about PEM which was measured with the DSQ-PEM :

This is always very useful to calibrate my own analysis. s-LDSC is quite complex to set up and I certainly could have made a mistake. But I tried to redo their schizophrenia and tiredness analysis and my and their coefficients and p-values correlate at 0.99 so that hopefully means my DecodeME...

Same with tiredness, which looks quite different than ME/CFS in this dataset. The data on tiredness came from the UK biobank using the question: "Over the last two weeks, how often have you felt tired or had little energy?" Source: Deary et al. 2017 Genetic contributions to self-reported...

From the talk around minute 27. Pretty much all autoimmune disorders show a peak and association to HLA, ME/CFS apparently doesn't.

Their data is in supplementary table 26. I only selected a couple of their traits (many used older and underpowered GWAS) but here's the plot with all of them included. The MSN peak is prominent also in substance disorders such as alcohol and tobacco usage.

Did an analysis of the chromatin openness (sc-ATAC-seq) rather than RNA in the brain atlas by Li et al. 2023. The main results look like this: For the full analysis see the thread here: A comparative atlas of single-cell chromatin accessibility in the human brain, Li et al, 2023 | Science for ME

I think this supports the findings of the RNA analyses we did earlier. You can find an overview of these here: Overview of RNA datasets for tissue and cell type enrichment analysis | Science for ME All neuronal traits show peaks at the Intratelencephalic projecting neurons, just like ME/CFS but...

This is similar to the Siletti 2023 brain atlas that we've been analyzing in relation to DecodeME, but instead of gene expression (RNA), the data points to chromatin openness using snATAC-seq. Chromatin is what packages DNA and more open regions suggests more gene transcription and activity. It...

Abstract Recent advances in single-cell transcriptomics have illuminated the diverse neuronal and glial cell types within the human brain. However, the regulatory programs governing cell identity and function remain unclear. Using a single-nucleus assay for transposase-accessible chromatin using...

Looks like they require an Institution or Organization Email. https://searchmecfs.org/User/Register

Great, thanks!

Does anyone know if, where and when videos of the PRIME workshop will become available? I missed it but it sounds very interesting. I wouldn't see this as a replication then, it's probably just DecodeME driving the signal in the meta-analysis due to its large sample size. I look forward to...

I'm not too keen on this eQTL analysis myself though because it's also influenced by window size and the most important genes might not show a lot of variation and thus eQTLs.

Think it would look something like this. - Using the GTEx API, I checked for genes that have their transcription start site within 1 MB of one of the FUMA-intervals for one of the DecodeME hits. - For each of those genes, I used the GTEx API to check whether it had a significant association...

Thanks, look forward to this analysis! Hope the UK biobank access is reopened soon (can imagine it must be a very frustrating situation for your team). In some sense, it might be good news that fewer genes show PPH4 coloc as it might lower the number of potential causal genes.

Coloc problem I think there might be an issue with the colocalization analysis and Figure 4 in the DecodeME preprint. This is important because these results determined whether a candidate gene is considered Tier 1 or not. In brief, In think the paper used only the significant SNPs from the...

Yes I think a replication of DecodeME in Germany with a possible whole-genome-sequencing follow-up like sequenceME would make a lot of sense. It was just relatively cheap: around 3.2 million pound (compare that to the 1000 million that has been spent on LC research and what came out of that)...

Yes this looks like what is needed: https://www.dzne.de/en/research/brain-bank/ A well-funded ME/CFS program within DZNE brain bank would make a lot of sense. You need an experienced institute to organize all the consent forms and collect the brain samples in time.

The genetic findings of DecodeME strongly pointed towards the brain and the autopsies from the Netherlands have reported notable findings. So I think a priority should be to collect brain tissue from ME/CFS patients.

Yes