Preprint Initial findings from the DecodeME genome-wide association study of myalgic encephalomyelitis/chronic fatigue syndrome, 2025, DecodeMe Collaboration

That's a really useful article @ME/CFS Science Blog - thank you. Looking forward to the next in the series. I'll try and find some articles that tie identified genes to the new post-synaptic AMPA receptor findings (X looks like it marks the spot quite nicely).

I spotted one instance of "DecodeMe" instead of "DecodeME" (also a few "Decode" abbreviations that may be intentional). I'd also change "it’s what they are pointing to what matters!" to "it’s what they are pointing to that matters!"
 
SNT Gatchaman said:
That's a really useful article @ME/CFS Science Blog - thank you. Looking forward to the next in the series. I'll try and find some articles that tie identified genes to the new post-synaptic AMPA receptor findings (X looks like it marks the spot quite nicely).

I spotted one instance of "DecodeMe" instead of "DecodeME" (also a few "Decode" abbreviations that may be intentional). I'd also change "it’s what they are pointing to what matters!" to "it’s what they are pointing to that matters!"
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Updated, thanks!
 
Andy said:
Blog: DecodeME: the biggest ME/CFS study ever

mecfsscience.org

DecodeME: the biggest ME/CFS study ever - ME/CFS Science

The first results of DecodeME are in, the largest research project ever undertaken on myalgicContinue readingDecodeME: the biggest ME/CFS study ever
mecfsscience.org mecfsscience.org
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Really good blog, as always @ME/CFS Science Blog

Some minor issues, comments and suggestions:

“Human DNA has 3.2 billion of these ‘base pairs’, but most of them are not relevant or the same in everyone.”

Human DNA has 3.2 billion of these ‘base pairs’, but most of them are the same in everyone or not relevant.

[Avoids ambiguity]


“If your data doesn’t include the top SNP, you can check one of the SNPs nearby that is highly correlated with it.”

Not quite sure what this means. What is “your data”?


“Humans have around 20.000 to 25.000 genes.”

20,000 to 25,000 not 20.000 to 25.000


“In the graph, we use the -log10 of p-values, so the higher on the plot, the lower the p-value, and the more unusual the SNP.”

Long dash without space (–log10) or write negative. I was confused because on my screen there was a line space between the - and log10. The graph should also indicate this.

“Indeed, the difference in prevalence of SNPs hits is only about 1% to 2% between patients and controls.”

I think you mean percentage points. The difference between 34% and 32% is 2 percentage points but approximately 6%.


“A recent paper in Nature backs this up. It examined data on drug development and found that effect sizes from genetic studies did not influence the chance that a drug will be successful.”

Perhaps make it clearer that you mean the size of the effect doesn’t matter, providing there is an effect.


“With another tool called ‘LD Score Regression (LDSC)’, we can also look at the genetic correlation between ME/CFS and other diseases registered in the UK Biobank.”

You use capitals so the inverted commas are redundant.


“There were substantial correlations with many illness categories, especially those related to gut problems, fatigue, pain, and depression.”

I thought the pre-print suggested there was no overlap with genes associated with anxiety or depression. I’ve not managed to keep up with discussions. Is that now considered to be inaccurate?


“There were also significant correlations with schizophrenia (rg = 0.53)”

I didn’t know that. I wonder if ME/CFS could tell us something useful about the mechanisms of schizophrenia.


“Lastly, DecodeME also provided an estimate of the heritability of ME/CFS, which was 9.5%”

I wonder if you should have explained what heritability of 9.5% means.


“DecodeME also looked at the common SNPs only where the frequency of the minor allele was 1% or higher.”

Also, DecodeME only looked at the common SNPs where the frequency of the minor allele was 1% or higher.


Thanks again. I’m looking forward to reading your next blog.
 
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neophyte32 said:
If it's a brain problem, there's not much we can do, right? Could it be invisible lesions with our current technology?
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You could say that of cerebral lupus, or autoimmune encephalitis, which are eminently treatable these days. And if it is a problem capable of remission, which we think it is, then maybe there are no lesions as such and all that is required is an alteration in chemistry.

Hypothyroid effects on the brain (the original meaning of cretinism, when congenital) are entirely reversible with thyroxine. We are not yet quite so good at re-balancing chemicals in Parkinson's or depression but lithium certainly works in some conditions.

And the brain problem may still be dependent on peripheral signals from innate immune cells, which we may be able to block.
 
ME/CFS Science Blog said:
Thanks @Robert 1973
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One thing that your blog didn’t mention was sub-groups. I haven’t managed to keep up with discussions but as far as I understand the data from DecodeME doesn’t yet tell us whether ME/CFS is likely to be more than one disease, or anything about sub-groups. I’m not sure if this is something that may emerge with further analysis or whether we would need WGS for that.

Apologies if this has been discussed and I’ve missed it.

Edit: typo
 
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Robert 1973 said:
One thing that your blog didn’t mention was sub-groups. I haven’t managed to keep up with discussions but as far as I understand the data from DecodeME doesn’t yet tell us whether ME/CFS is likely to be than one disease, or anything about sub-groups. I’m not sure if this is something that may emerge with further analysis or whether we would need WGS for that.

Apologies if this has been discussed and I’ve missed it.
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The summary data that DecodeME has made available doesn't include or allow for subgroup analyses. It doesn't include the raw data and questionnaire data to do this. So it will be up to the DecodeME team to publish more on this.
 
Robert 1973 said:
One thing that your blog didn’t mention was sub-groups. I haven’t managed to keep up with discussions but as far as I understand the data from DecodeME doesn’t yet tell us whether ME/CFS is likely to be than one disease, or anything about sub-groups.
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I would like to see whether the 8 gene loci SNPs come up more or less often in combination with each other - do we see the linked allele for OLFM4 more often than by chance with that for CA10 or less. How you read the answer would be complicated but if it was cler cut it might be less so.
 
Precision Life have the data and are into the idea of subgroups. Difficult for us to interpret given their analysis methods are a black box and they don’t seem great at communicating with us. But if they show some subgroups with the same data and can explain and perhaps tie it to the same identified genes… could be interesting
 
DMissa said:
I was yesterday reading a recent nature paper about mechanisms by which this may occur as tested in mice: https://www.nature.com/articles/s41586-024-07469-y

The abstract etc are full of buzzwords but the actual experiments seem interesting.
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Yes, this paper might deserve a thread. It claims to have identified pathways both from peripheral inflammatory insult to brain and back again.

The mystery is how in ME/CFS this would work without any actual ongoing inflammatory stimulus and no circulating cytokine changes. But that may not mean the pathways are not relevant.
 
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