Preprint Biological Insights from Genome-Wide Association Studies and Whole Genome Sequencing of [ME/CFS], 2026, Maccallini et al

[forestglip]

Yes, this dendrogram is based on genetic data. More precisely, I used the genes found by PrecisionLife using the DecodeME cohort plus the genes found by Mark Snyder from WGS of 200 or so ME/CFS patients. I then collected genes form the latest GWAS and rare variants studies for other 27 common diseases.

Might it make sense to make a dendrogram using the raw SNP p values from the whole genome? I don't know how to do it, but it seems like it could be less affected by differences in how studies pick genes (e.g. PrecisionLife's method vs other GWAS using nearest gene).

 

[duncan]

It is simply not possible to tell from observing your symptoms that you have a degenerative disease.

Over 30 years? Sure it is. I've steadily seen my IQ drop over the years. The last I checked, it was down 20 points over premorbid levels. Now, it may be fair to claim those are objective tests, but I can feel my Stupid, much as I can the sense of poison that courses through me that no one can capture in any objective lab.

But if you know where to look, and have the right technology, can you actually demonstrate it in pwME? I think you can, but you better be looking hard for it. How many have access to a Tesla 5 or 7? I did, through the NIH, and it repeatedly revealed brain atrophy, albeit subtle. Fortunately, they were looking for something, they just didn't know what. And my results took them off guard.

How many of us recover to healthy status? 5%? Less? We haven't merely deteriorated, we've loss a varying degree of function - forever.

And for a portion of us, that degree, with speed bumps, only worsens over time. It's just the rate that varies when you've that brand.

Fortunately, that is a small portion of pwME.

I deteriorate with the flu. ME/CFS for me was degenerative.

ETA: My wife has ATS. She has seen only one neurologist in the least 30 years. She has forever refused to read the studies, or look at the science. She doesn't want to know. Do you imagine she doesn't for a second know that her body is slowly failing her in a degenerative fashion?

 

[Verity]

Over 30 years? Sure it is. I've steadily seen my IQ drop over the years. The last I checked, it was down 20 points over premorbid levels. Now, it may be fair to claim those are objective tests, but I can feel my Stupid, much as I can the sense of poison that courses through me that no one can capture in any objective lab.

But if you know where to look, and have the right technology, can you actually demonstrate it in pwME? I think you can, but you better be looking hard for it. How many have access to a Tesla 5 or 7? I did, through the NIH, and it repeatedly revealed brain atrophy, albeit subtle. Fortunately, they were looking for something, they just didn't know what. And my results took them off guard.

How many of us recover to healthy status? 5%? Less? We haven't merely deteriorated, we've loss a varying degree of function - forever.

And for a portion of us, that degree, with speed bumps, only worsens over time. It's just the rate that varies when you've that brand.

Fortunately, that is a small portion of pwME.

I deteriorate with the flu. ME/CFS for me was degenerative.

But you could say these sorts of things about illnesses that we know are not degenerative. I’m not seeing the connection. I was in graduate school when I got sick and have felt very stupid compared to my past self for years! But I started Ritalin recently and regained lot of cognitive function.

I am not sure how interpretable one test showing brain atrophy is. Someone else can weigh in if they think it’s really definitive.

(I think we’d better take this to a different thread if we want to discuss whether ME is degenerative because it may be getting off track here.)

 

[wallfish]

View attachment 32485

Is my interpretation correct that the closeness between Obesity and Sleep Disorder can be attributed to something like Obstructive Sleep Apnea, while the closeness between MECFS and Sleep Disorder is likely due to a different kind of relationship?

Obesity and MECFS are clustered together, but maybe deceptively so?

I might be wrong, I am not familiar with the data or the process. Only glanced the figure. I'm interested because I struggled in the past to create meaningful dendograms (in the sense of identifying some known relationship instead of false friends) with text embeddings.

 

[duncan]

But you could say these sorts of things about illnesses that we know are not degenerative. I’m not seeing the connection. I was in graduate school when I got sick and have felt very stupid compared to my past self for years! But I started Ritalin recently and regained lot of cognitive function.

I am not sure how interpretable one test showing brain atrophy is. Someone else can weigh in if they think it’s really definitive.

(I think we’d better take this to a different thread if we want to discuss whether ME is degenerative because it may be getting off track here.)

What percent of us return to our premorbid levels? We don't.

So perhaps the initial insult caused mci, or other damage, and then we level set. Maybe.

But I feel worse, and that's my metric after studying all these studies about so many of us and folk like us for far too many years.

BTW. I've three MRIs that show atrophy.

 

[MrMagoo]

Yes, I’ve also heard that for some, but at the same time there are also people like this.

We’d have to be able to explain both.

What would be degenerating? We haven’t found it yet at least.

I absolutely feel that mine started years before. But I also was running regular 10k, working, studying at night, travelling the world and considering whether to try and do a marathon when I became ill. Not long before I won a prize for most regular attendance at my gym. I had also been struggling with getting more frequent colds/bugs, every few months I’d feel like I was hit by a virus…sound familiar?

 

[Axel]

The link with diabetes is unclear to me. Same applies to obesity. One may argue that if you are sedentary because of ME/CFS, you are susceptible to obesity and diabetes.

Behaviour doesn’t alter genes; that’s what makes these comparisons and parallels so interesting. ME/CFS turns out to be on an unexpected side that will provide further clues.