PRIME International Symposium, September 28-29 2026

[V.R.T.]

Altmann didn't give any data from WILCO in his talk but he did say transcriptomic pathways differed between people who eventually recovered, stayed the same and got worse 'in a rather good and exciting way'.

He also said they were currently writing up multiple papers from WILCO.

I appreciated him (politely) giving LC researchers a hard time for being blinkered about their particular hypotheses and overstating their findings.

 

[V.R.T.]

I watched the presentation by Hanna M. Ollila titled "The Future of MECFS Genetics". She gave a good impression and presented findings from the big meta-analysis. Here's the direct link to the video:
EDIT: I've updated the images to versions with a better resolution.


The meta-analysis has 60,542 cases and 2,766,590 controls. Based on the slides, they included cases based on self-reported chronic fatigue and those with a diagnosis pos-viral fatigue syndrome. So a wider net than just ME/CFS.
View attachment 34712

Here's the Manhhatten plot. Despite the large increase in cases, they found (only) 11 loci (DecodeME's primary analysis found 6 hits with ca 15.000 cases).
View attachment 34713

One of the more interesting findings is that the pituitary (green bar below) now stood out in the tissue analysis.
View attachment 34714


They also found large genetic correlations between Long Covid and ME/CFS and Long Co id and fibromyalgia. ALthough I'm not sure how they end up with values of rg = 0.99 and if these are reliable. The standard errors also look quite large, suggesting there may be an issue with this calculation (perhaps due to the low heritability h^2)?
View attachment 34710

Lastly, they also report that ME/CFS also had correlations with other post-infectious traits.

View attachment 34715

I stil have doubts with this wider net approach but it does look interesting and might offer a slightly different perspective. Perhaps it would be worthwhile to do a meta-analysis by combining ME/CFS, LC and fibromyalgia samples.

A hit on chromasome 6 here - OR2J3-HLA-A

 

[ME/CFS Science Blog]

A hit on chromasome 6 here - OR2J3-HLA-A

Yes, exciting! Ollila said about it: "note also that there is a potential HLA association that is just before HLA-A that we're also going to finemap."

Looks like DecodeME also had signal here with a p-value around 5*10^-6.

The locus is probably around 29 MB on chromosome 6.
The BTN hit in DecodeME isn't too far of at 26.26 MB on the same chromosome but probably too distant to be considered one signal.

 

[tralfamadorian97]

I still have doubts with this wider net approach but it does look interesting and might offer a slightly different perspective

Yes. I think understanding whether this wider net approach is or is not valid is very important. We want to know the extent to which any of the various biobank cohort phenotypes are approximately capturing the the same disease as is measured in DecodeME. The earlier Targene-based analysis seemed to suggest some incompatibility between DecodeME and certain UK Biobank/ All of Us phenotypes. For the cohorts in Ollila's study, I would be interested in seeing:

• Cross-cohort replication checks of key GWAS hits
• (When cohort sample size allows) Genetic correlation between the meta-analyzed cohorts, and between each cohort and a set of external traits.
• Leave-one-cohort-out analysis: If we have N cohorts, repeat the analysis N times, each time with one of the cohorts dropped. How do the meta-analysis results change?

I also believe there are some statistical tests designed to measure compatibility between different GWAS. It would probably be informative to apply these as well.

 

[hotblack]

The earlier Targene-based analysis seemed to suggest some incompatibility between DecodeME and certain UK Biobank/ All of Us phenotypes.

Understanding what is down to different phenotypes and what is down to different analysis methods will be important too. We haven’t seen like for like with only one variable changing so can’t be sure where the differences are coming from IMHO. It could be a combination of both.

 

[Braganca]

I’m unable to watch all of it, or take in and remember everything I did watch, but didn’t seem to see mention of the brain, nerves, synapses, abnormal brain signaling etc as priorities among any of the researchers. Focus still seems to be on immune system among people taking biological samples. Is that bc synapses and brain are too hard or not feasible with current technology? Or did I miss mention of these things?

 

[Jonathan Edwards]

Focus still seems to be on immune system among people taking biological samples. Is that bc synapses and brain are too hard or not feasible with current technology? Or did I miss mention of these things?

The next webinar is on neurology. I think this symposium mostly covered stuff already in progress (although not entirely) and the neurological stuff is only just being set up. Technology for neurological studies exists, at least for some avenues, and interest seems to be building.

 

[ScoutB]

Slowly making my way through the videos. @audrey_ryback (et al)'s work with long term electronic health record data looks like it'll be really informative. Sounds like we may get info similar to that MS study that reported an increase in doctors visits years before people finally received their diagnosis. And I imagine the bacterial infection association could be a clue as well. Looking forward to hearing more:


(Also was heartened by the back and forth during a later session discussing how ME/CFS research could be done better. One fellow answered we need *less* large cohort studies and more studies where we collect reams of data from small groups of patients, and I was grateful Audrey replied pointing out we have been doing that -- it's why we have a replication crisis.)

Hannah Maude's speed talk on chromatin openness at the chr20 decodeME hit also sounded interesting (and mentioned T cells). I know @ME/CFS Science Blog did a similar-sounding analysis as well, though I'm too foggy at the moment to follow exactly what they've each done.

 

[Chandelier]

From Bluesky:

---

Chris Ponting @cgatist.bsky.social

Recordings of the 2026 PRIME Symposium talks are now available to view:

#pwME #MEcfs

Also: PRIME's 4th online webinar, The Neurology of ME/CFS, will take place on Wed 28th October, 2026 at 2pm-5pm GMT.
Register here: https://www.actionforme.org.uk/register-for-the-4th-prime-webinar-the-neurology-of-me-cfs/
​

---

 

[chillier]

Slowly making my way through the videos. @audrey_ryback (et al)'s work with long term electronic health record data looks like it'll be really informative. Sounds like we may get info similar to that MS study that reported an increase in doctors visits years before people finally received their diagnosis. And I imagine the bacterial infection association could be a clue as well. Looking forward to hearing more:
View attachment 34729

(Also was heartened by the back and forth during a later session discussing how ME/CFS research could be done better. One fellow answered we need *less* large cohort studies and more studies where we collect reams of data from small groups of patients, and I was grateful Audrey replied pointing out we have been doing that -- it's why we have a replication crisis.)

Hannah Maude's speed talk on chromatin openness at the chr20 decodeME hit also sounded interesting (and mentioned T cells). I know @ME/CFS Science Blog did a similar-sounding analysis as well, though I'm too foggy at the moment to follow exactly what they've each done.
View attachment 34730

@jnmaciuch We talked briefly in the past about whether specifically the pathogen, in particular EBV, mattered in ME/CFS. I think your opinion was EBV infection specifically could matter but correct me if I'm wrong. My current feeling is that the pathogen does not matter, but it's the response to an infection instead that matters - which could be generic. Partly because infection does not appear to be necessary for ME/CFS at all (in 40% of people in the EMEA 2021 survey).

There's some data Audrey is showing here that I think is relevant. I thought it was quite interesting that - in this cohort at least - viral, bacterial infections and glandular fever were more often reported prior to ME/CFS onset than controls and with similar effect sizes. ME/CFS is talked about being post viral quite a lot but the reason for that in this dataset appear to be because bacterial infections are less common just in general. Also interesting is that glandular fever is more often an occurrence pre-ME/CFS than pre-MS, despite EBV having a causal role in MS. These things seem to imply it could be that having a big infection with an associated immune response is the trigger in post infectious ME/CFS, not the pathogen.

 

[Utsikt]

We’ve also seen people develop ME/CFS after vaccines. It’s less common that after infections, but it points towards immune system activation being the important part, and not what activates the immune system.

 

[jnmaciuch]

@jnmaciuch We talked briefly in the past about whether specifically the pathogen, in particular EBV, mattered in ME/CFS. I think your opinion was EBV infection specifically could matter but correct me if I'm wrong. My current feeling is that the pathogen does not matter, but it's the response to an infection instead that matters - which could be generic. Partly because infection does not appear to be necessary for ME/CFS at all (in 40% of people in the EMEA 2021 survey).

There's some data Audrey is showing here that I think is relevant. I thought it was quite interesting that - in this cohort at least - viral, bacterial infections and glandular fever were more often reported prior to ME/CFS onset than controls and with similar effect sizes. ME/CFS is talked about being post viral quite a lot but the reason for that in this dataset appear to be because bacterial infections are less common just in general. Also interesting is that glandular fever is more often an occurrence pre-ME/CFS than pre-MS, despite EBV having a causal role in MS. These things seem to imply it could be that having a big infection with an associated immune response is the trigger in post infectious ME/CFS, not the pathogen.

Thanks for bringing this to my attention, I will definitely check it out!

I don’t remember the specific conversation but I’ve suspected in the past that certain pathogens might have features during the acute infection stage that predispose more to ME/CFS than other pathogens. Which may be due to things like anatomical compartment specificity, or cell types/particular pathways that are more or less stimulated by the infection response. So I agree that it’s probably a generic response that doesn’t need a specific pathogen but the pathogens most associated with ME/CFS onset might give us some clues.

I think it would be useful to drill into what it means to have a “big infection” since the severity of the initial infection doesn’t seem to matter much, at least for post-COVID ME/CFS. And duration of the infection itself doesn’t provide a clear signal otherwise we might see a clear association with something like chronic Hep C. Even people on anti-retrovirals for HIV can have long term low-level immune activity in the CNS from sporadic reactivation but that tends to present first and foremost as marked memory issues and motor decline rather than something that looks like ME/CFS. So it must be some specific feature of an infection (or other trigger) that isn’t necessarily the magnitude or length of the immune response. But I will save more of my thoughts until after I’ve had a chance to look at this!

 

[V.R.T.]

Hannah Maude's speed talk on chromatin openness at the chr20 decodeME hit also sounded interesting (and mentioned T cells).

@ME/CFS Science Blog and @jnmaciuch you might both find this brief talk interesting.

 

[V.R.T.]

Hannah Maude's speed talk on chromatin

Maude mentions a poster that goes into more detail and has a hypothesis on at the end of her talk - is this/will this be publically available?

 

[Axel]

So it must be some specific feature of an infection (or other trigger) that isn’t necessarily the magnitude or length of the immune response

I am curious to know if that there might be differences in the extent to which innate immune system is involved depending on the infection. It could be a factor behind the increased risk. This is just a line of thought.
We would nevertheless need to identify these factors. I often think of the people who might have remained asymptomatic had they not contracted Covid-19. If it's just probabilities to be infected, there is nothing to do but protect oneself everyday, if you have to avoid certain type of infection... It is not the same.

 

[Andy]

Maude mentions a poster that goes into more detail and has a hypothesis on at the end of her talk - is this/will this be publically available?

I'm not aware that there is any intention for PRIME to publish them, however she might be willing to share if contacted directly.

 

[jnmaciuch]

There's some data Audrey is showing here that I think is relevant.

I've watched the short talk now and have a million follow-up questions! If there's a paper in the works, that might answer most of the methodological ones.

I'd be interested to know the N for bacterial infections across all 3 groups, the high odds ratio just for MS is particularly striking. And if this data gives a hint for the specific viral or bacterial infections that were driving the signal, that would be really interesting to know.

@audrey_ryback would it be possible to share the information you withheld at the end on here (I'm assuming about mortality), or is it still too public? (And thank you for your work on this!)

 

[ChronicallyOverIt]

ME/CFS is talked about being post viral quite a lot but the reason for that in this dataset appear to be because bacterial infections are less common just in general. Also interesting is that glandular fever is more often an occurrence pre-ME/CFS than pre-MS, despite EBV having a causal role in MS. These things seem to imply it could be that having a big infection with an associated immune response is the trigger in post infectious ME/CFS, not the pathogen.

I do wonder if the bacterial signal is small due to antibiotics, as in the infection is wiped out early on, say for strep, and the "loop" that causes ME/CFS never has time to set up.

 

[V.R.T.]

I do wonder if the bacterial signal is small due to antibiotics, as in the infection is wiped out early on, say for strep, and the "loop" that causes ME/CFS never has time to set up.

When we got our triggering infection(s) for our definite onset (we both had possible prodromal symptoms), which was a strep infection and an impetigo infection, iirc two different bacterial strains, my partner went to doctors, got swabbed for strep and got on antibiotics, whereas I got treatment for the impetigo but when the strep hit me I was too unwell to get myself there (should have taken a taxi in retrospect) and by the time I got throat swabbed a couple weeks later the infection had run its course and I didn't test postive. We both got MECFS.

In fact, my partner got several courses of antibiotics over the next year or two because of recurrant tonsillitis and still wound up with MECFS.

I got barely any antibiotics because my tonsils were red and inflamed but without visible pus for a year and nothing was coming up on swabs, and then I had a bad reaction to antibiotics when the visible white marks did appear.

She was a little more severe than I was until 2020 (mild/moderate to my mild).

Maybe gone into too much detail but thought it might be useful to someone.

 

[Axel]

Maybe gone into too much detail but thought it might be useful to someone.

It’s the issue of a secondary infection. I, too, had several bouts of flu in quick succession, plus a bacterial infection. After that, I never recovered.