Preprint Cluster analysis of ME/CFS symptoms in DecodeME reveals two subgroups and a link to onset type, 2026, St-Jean et al

[tralfamadorian97]

Though I don't understand what those smaller numbers are based on, and why not all 15,328 would be included.

I agree. I would like more detail on the participant numbers.

 

[tralfamadorian97]

If I am reading correctly, it sounds like the authors ran a conditional GWAS of symptom burden among DecodeME cases. I am wondering whether this GWAS might be vulnerable to the kind of collider bias as discussed in this paper

 

[Jonathan Edwards]

Could there be a clue to bistability / mechanism .
I don't know if we have data for this.

It makes sense. Whether you can set up the cohorts in a way that you can get good statistics or not I wouldn't be sure.

 

[Simon M]

Percentage of patients in the HSBC per severity (and ratio (HS/LS)):

Mild/moderate: 53 % (1.15)
Severe: 80 % (3.98)
Very severe: 83 % (4.86)

Granted, there are only about 2500 severe and 150 very severe patients.

Thanks for this helpful reply.

I've been digging more into the numbers, and I'm not sure that the High symptom burden cluster is so much more severe than the low one.

This is the data from the supplementary table showing illness severity by symptom clusters. Please should if I have made any errors (you know what I'm like with typos etc. The stand out finding for me is that while the rate of severe and v severe illness is 3 x higher in the high symptom cluster, 80% of that still rate themselves as mild or moderate severity.



Another way to measure severity is to simply allocate a score to each severity level from 1 for mild to 4 to severe. And on this measure, the average symptom score difference is rather modest: 1.7 for low symptom vs 2.0 for high, Though 6.3% in the Low cluster are severe vs 19.5% in the High cluster.


Symptom burden differences are reflected in significant but not huge illness severity differences, and a large majority in the High cluster are mild or moderate overall. So I wonder if "symptom burden" is an ambiguous term, and "symptom count" would be more accurate/less confusing.

Again, please shout if my numbers are wrong.

 

[Peter T]

It looks like that in my browser (Safari on an iPad) some of the data has fallen out of the tables, making them very confusing,

 

[Utsikt]

Thank you @Simon M

I think something might have gone wrong with you tables, or my mobile browser is really messing with how it’s being displayed.

I agree that «symptom burden» is not ideal when talking about the number of symptoms and not the severity of symptoms. «Symptom count» like you suggest is much clearer.

My angle with my crude analysis was that you are much more likely to have a higher symptom count if you’re severe compared to being not severe. So not only do you have more severe symptoms, you also on average have a larger variety of symptoms to deal with.

 

[Simon M]

I think something might have gone wrong with you tables, or my mobile browser is really messing with how it’s being displayed.

It looks like that in my browser (Safari on an iPad) some of the data has fallen out of the tables, making them very confusing,

Apologies - that looked great on my laptop, but what a mess. Now as screenprints, repeated below:

I agree that «symptom burden» is not ideal when talking about the number of symptoms and not the severity of symptoms. «Symptom count» like you suggest is much clearer.

My angle with my crude analysis was that you are much more likely to have a higher symptom count if you’re severe compared to being not severe. So not only do you have more severe symptoms, you also on average have a larger variety of symptoms to deal with.

I agree the severity difference is more impressive, and that having more severe illness tends to go with more symptoms too (though I think more severe symptoms can be at least as bad as more symptoms).

Separately, did you spot a symptom count threshold derived from the k clustering - presumably there is one?

But what struck me about the paper was that the clustering threw up a 2-cluster solution, even though 80% of the high-count cluster had moderate or mild illness. Which makes it harder to interpret, at least from my perspective.

 

[Utsikt]

Thanks! How is the H/L proportion ratio in the first table calculated? It’s not the same as my ration when diving the number or severe in high by the number of severe in low.

Separately, did you spot a symptom count threshold derived from the k clustering - presumably there is one?

I did not see it in the main text but I don’t trust me to not miss it in my current brainfogged state.

But what struck me about the paper was that the clustering threw up a 2-cluster solution, even though 80% of the high-count cluster had moderate or mild illness. Which makes it harder to interpret, at least from my perspective.

Keep in mind that high/low are relative descriptions with the entire cohort as a reference range. If you tried to determine the high/low threshold for only the severe (&vs) and then apply it to the mod (&mild) you’d get fewer of the mod in the high group.

Without knowing how the method actually works, I would assume that the symptom counts if the mild/mod are the ones that primarily influenced the threshold because they made up most of the population.

 

[Axel]

The stand out finding for me is that while the rate of severe and v severe illness is 3 x higher in the high symptom cluster, 80% of that still rate themselves as mild or moderate severity.

But might this not simply reflect the inability of patients with severe to very severe cases to pay attention to all sorts of milder symptoms? --in the case of what is reported is the number of symptoms and not the intensity.