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I don't think it does; merely wanted to suggest how it leaves room for it. It would view overexertion as the body not responding to the symptom signal. Hence, the need to make the symptoms worse and cause PEM. This would help explain why any type of exertion (cognitive tasks, physical exercise...

Yes, many patients also report early muscle weakness/cramping/lactic acid feeling that seems similar to what Ramsay described in his descriptions of ME. Anecdotally, severe patients also seem to suffer from muscle weakness that does not appear to be due to deconditioning. I'm not sure if these...

My hunch is to follow Ockham's razor, keep things simple, and only add things if we really need to. At this point, I think there is strong evidence of an immune trigger, but not necessarily of immune pathology maintaining the illness.

Thanks for all the useful comments and suggestions! Lowered intelligence, drop in IQ level. But I generally meant that ME/CFS does not suggest brain damage or a neural development disorder. The cognitive problems are disabling but more vague and diffuse in nature, such as brain fog. Like Jo...

Conclusion Overall, I think this is convincing evidence that should make this the most plausible framework for understanding ME/CFS. When I think about other theories for ME/CFS, they often fit into this concept as an addition (for example, by giving a plausible explanation of how the signaling...

Genetic data Let’s now move on to some actual data. The best evidence that we have is from genetic studies because of large sample sizes that control for population differences and that are not confounded by other factors such as diet, behavior, or the illness itself. If we look at all the...

I wanted to make a thread to discuss the theory that ME/CFS is a signaling problem, located in the synapses of neurons in the brain. I think it fits and would help explain the few findings and observations that we have about the illness. The clinical picture First of all, there is no clear...

For the hits on chromsome 1 and 20, there are so many potential genes on the location it's harder to guess which one might be relevant.

For the hit on chromosome 17, CA10 is the only candidate and it also clearly linked to neurons and synapses. So if we focus on the close-by genes, the clearest hits seem to point to neurons/synapses. The exceptions are OLFM4 on chromosome 13, which has a clear immune connection (linked to...

PEBP1 seems like the second closest to the hit on chromosome 12, next to TAOK3, which seems very stretched out. EDIT: added the image below

Another gene that hasn't been discussed yet but that seems the closest to the hit on chromosome 6q is POU3F2 POU3F2 Gene - GeneCards | PO3F2 Protein | PO3F2 Antibody EDIT: added the image below

Highlighting gene UNC13C, which seems the closest to the hits on chromosome 15. The gene card reads as follows: UNC13C Gene - GeneCards | UN13C Protein | UN13C Antibody EDIT: added the image below

This lecture is interesting and relevant to our discussion: MPG Primer: Linking SNPs with genes in GWAS (2022) Don't understand everything, but there's some discussion that eQTL data and GWAS hits often do not match very well. Genes that are likely to be causally related to disease often do not...

If these experiments could show that the problems likely do not lie in the muscles itself (peripheral fatigue): wouldn't that affect theories about mitochondrial and endothelial dysfunction as being less likely causes of ME/CFS symptoms?

They did this in the intramural NIH study (some of the participants in this paper were healthy controls in the ME/CFS study). They reported that ME/CFS patients had faster declines in grip strength but that there were no signs of peripheral fatigue. This reported the slope of the Dimitrov...

This is fascinating @forestglip ! I'm quite a bit behind in my understanding of MAGMA and FUMA compared to you, but I will try to catch up. Based on what you posted, the evidence seems quite persuasive that the differences found in DecodeME (not just the 8 hits) point to something happening in...

Looks like the accuracy of imputation is usually > 95% in common variants in European populations (although I found it quite hard to find the numbers on this. I suppose it's easy to test: you could just deleted a portion of what you measured and then try to impute them.)...

Of the 8 hits, only 1 was measured, but the others have a high INFO_SCORE suggestion that their distributions follow Hardy-Weinberg Equilibrium. I suppose it's based on the strong correlations between SNPs that you only need to know a few to be pretty certain what the others are. But I was...

My understanding is that only ca. 820.000 SNPs were measured, and approximately half of these were discarded because of bad quality. The other 8 million were imputed. See Chris his response here...

Impressive! Is this with the dataset filtered for quality control or the full dataset?