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I'm not able to comment on the new thread that discusses MAGMA (It says: "You have insufficient privileges to reply here.") Using MAGMA on ME/CFS genetic data | Science for ME EDIT: Fixed now! But having downloaded the FUMA processed files here, I think Forestglip is right...

There was a paper from the group of Andreas Goebel who first demonstrated this transfer of IgG effect in fibromyalgia. They argue that "FMS-IgG binds to mast cells in a MRGPRX2/b2-dependent manner, leading to mast cell recruitment and IL-6 secretion. [...] The ablation of mice Mrgprb2 mast...

My guess is that it only tested one of the less notable eMSN such as those in the cerebral cortex but not those in the striatum and amygdala, which is where most eMSNs are and where most of the significant results came from.

The inclusion criteria were Fukuda, but with PEM required. Here are the main results, showing almost no decline at all in the ME/CFS patients. The text also mentions workload at VT, which was the most replicated finding thus far. The authors argue that the previous study by Keller et al...

Thanks. Do you know which eMSN cell type this was and from which database? Because both the 461 and 2082 clustering from the Siletti atlas resulted in eMSN cell types with p < 10^−6, if I recall correctly.

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