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I can see there might be variation in the brain cell samples as Siletti et al. only used 4 donors. So the clustering and gene expression per cluster might be slightly different if this was done again. But the same reasoning likely applies to GTEx tissue expression or eQTL-based mapping that the...

Some counterpoints: - The MAGMA analysis shows that the eMSN clusters have high BETA, BETA_STD and SE. So when estimating the slope between gene-associations with ME/CFS and gene expression in the cluster, they had high effects and high variation. So the p-value likely wasn't due to higher...

Curious what the explanation might be that antibodies from LC are more likely to cause pain sensitivity in mice compared to antibodies from convalescent controls. Several groups have reported this now. Looks like this group did in-depth measurements to figure out what causes this but that they...

Made this summary of the paper. 1) Impressive paper from Iwasaki’s lab pointing at autoimmunity in a subgroup of Long Covid patients. They replicated previous experiments of antibody transfer causing symptoms in mice. A couple of findings that stand out… 2) They extracted antibodies from...

Thanks, quite a lot of differences unfortunately. Did it only focus on the hits above 5*10^-8?

Yes ranked according to p-value of the locus where they were predicted to be the causal gene. The loci with the lowest p-value (strongest signal) are on top. The Excel file on the other thread gives more information.

We managed to apply the FLAMES machine learning algorithm to DecodeME data. It helps to make a prediction which genes the DNA signal points to. For the significance threshold of 5*10^-8 there were only 6 DecodeME hits so I've reduced it to 5*10^-6 to get more potential genes. More info here...

I got slightly different results using the UK biobank LD panel (UKBrelease2b10kEuropean). I specified the full rather than effective sample size (n = 275488). FLAMES highlighted 31 instead of 32 causal genes (and VRK2 appears twice again, so it's 30 genes). The main differences are: No longer...

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...