Discussion in 'BioMedical ME/CFS Research' started by John Mac, Nov 5, 2020.
Like all Warren Tate studies, this seems to be done meticulously well, but on a very small sample. The finding that there was a 59% overlap of the specific genes identified in this study with other studies using (inferior) array-based technology, together with the clustering around types of pathways, suggest the findings might be relevant.
Hopefully this small study will help generate funding for a larger study that also looks at controls with relevant diseases.
Is this the sort of difference that the GWAS study would identify, @Simon M?
This is unrelated to the GWAS study. Tate is looking at how much genes are turned on or off, not what variants of genes there are to start with.
I agree with Simon that the study seems careful. The problem for me is that it is hard to know what to make of information about control of gene expression in white blood cells (many of which are doing nothing much or going nowhere) in the absence of something weight expect that to explain, like a raised CRP or fever or cytokine production changes in metabolic rate or whatever. The key thing about the GWAS is that it looks for things that were there before the ME started and which, if different in PWME, more or less have to be implicated, even if indirectly, in mechanism.
Summary with quotes:
Severely unrefreshing sleep on some days with no apparent pattern or cause was the first symptom I had. Only later did I develop ME/CFS.
Later on the unrefreshing sleep (of lesser severity) became part of postexertional malaise.
Although I can see how for example this methylation pattern might be due to the lifestyle of patients who spend a lot of time in front of blue light emitting screens because they can't do much else.
Also this summer I made sure to get a lot of sun and it seemed to be quite helpful (but I first had to get used to hot summer weather and felt worse for the first few weeks). When autumn arrived, I had a relapse.
No. These are differences in methylation of DNA - think of methylation as a tag that alters the activity of genes near the tagged DNA. So as @Jonathan Edwards says, it's about gene control (through methylation), not differences in DNA sequences that GWAS detect.
Oh, that is disappointing. Though I'm surprised only 76 fragments were more than 15% different between patients and controls out of 146,575 fragments, and that they clustered in what seem to be relevant areas to mecfs.
I would still like to see a much bigger study and one with disease controls.
@Simon M what do you think about the comparison to other studies? The authors say that a substantial portion of genes identified are the same across all the studies performed so far, with these studies utilizing different diagnostic criteria, recruiting patients from across a wide variety of ages and countries of residence. It seems encouraging that in all this heterogeneity there is a lot in common in terms of gene expression.
Would be grateful for a plain English translation. Anyone?
Looks like your wish is mirrored by the authors @Simon M. The bit I bolded reads to me as a plea for others elsewhere with better funding streams to follow up and expand on the results. Because funding in NZ goes like this:
So, a small local charity, an even smaller patient organisation plus private donations (from what I've heard they come in dribs and drabs leaving the team to live from week to week).
@DMissa - you get a few mentions in the paper. What's your take on it?
Hey Ravn, thanks for the tag. I hadn't seen this yet.
I've only had a quick read but the statistical approach seems to be commendable as others have already flagged. Good to see a new technical approach too.
So obviously, to discuss function/expression of specific gene products based on epigenetics, generally speaking, is inferential, so I won't go too deep. The authors have already done a nice job!
Just one or two points after first read:
It's interesting that Complex 1 overexpression is implicated again from a different angle.
The UCP2 hypermethylation is interesting. Uncoupling protein can be a major contributor to "proton leak" - pmf depletion not by ATP synthesis. In ME lymphoblasts this is elevated. If UCP is reduced in expression as is possible with the hypermethylation, it could indicate that something else is increasingly contributing towards proton leak. Could also still be a significant UCP contribution - remains to be seen.
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