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

[hotblack]

If the neurons were being influenced by antibodies, yes, otherwise probably no.

But they need not even have a direct influence, there could be an intermediary right? Some other signalling molecule for instance, interferon.

They don't really say anything about Fluge and Mella's work. Fluge and Mella might have rightly identified a B cell related mechanism that is more likely to give problems in people with certain genes affecting neuronal susceptibility. They might not. It would be a different part of the story.

I really do think there could be something here that helps fill in part of the picture, one of a few jigsaw pieces that will fit together and show us what this disease is all about.

It occurs to me that the situation with ME/CFS is not just the blinded scientists trying to describe the little bits of the elephant that they can feel, but that they are actually wandering around a waterhole, with the elephants there, but also the zebras and wildebeests and a few warthogs. Certainly that will be the case with the MVP cohort, with its relatively high CFS incidence. It does feel, though, that we are getting closer to identifying at least one of the diseases included under a CFS label.

I like the elephant comparison. But also keep coming back to the clockwork idea. Where we’re going to need to understand the interactions of multiple cogs and which wheels have which teeth missing or are spinning faster or slower than normal. I think most people who come under the label could well have the same disease just with different cogs more or less prominent in their biology.

 

[V.R.T.]

I think most people who come under the label could well have the same disease just with different cogs more or less prominent in their biology.

This makes a lot more sense to me than the idea there's lots of different diseases.

But they need not even have a direct influence, there could be an intermediary right? Some other signalling molecule for instance, interferon.

In the eMSN thread @ME/CFS Science Blog points out that BTN2A1 is quite highly expressed on eMSN.

 

[Hutan]

On the eMSN thread @ME/CFS Science Blog talks about the likelihood of poor characterisation of the MVP CFS sample. I think it is quite likely that the characterisation is poor, and that's why I think there may well be a mixture of diseases in that sample. We've had people on the forum, believing that they have ME/CFS and then finding that they have another disease that probably explains their symptoms.

ME/CFS Science Blog also mentions that the very large number of controls that the MVP database contributes makes a big difference to improving the ability to identify what it is about the DecodeME ME/CFS+ MVP CFS sample that is different to the controls. That makes me wonder about adding in more control groups.

Say if you take the controls from the UK Biobank of European ancestry, could they be usefully added to the control group? Presumably the bigger the control group, the better the identification of what it is that makes the ME/CFS group different. We can probably be fairly certain that the UK Biobank participants who aren't in the ME/CFS group don't have a strong genetic predisposition to ME/CFS, because they are over 50 years old.

 

[ME/CFS Science Blog]

Say if you take the controls from the UK Biobank of European ancestry, could they be usefully added to the control group?

As I understand it, these are the controls already used in DecodeME.

 

[Jonathan Edwards]

But they need not even have a direct influence, there could be an intermediary right? Some other signalling molecule for instance, interferon.

Sure.