SequenceME genetic study - from Oxford Nanopore Technologies, the University of Edinburgh and Action for ME

[Axel]

but there are cases younger than that, I think as young as five.

I think I’m one of them. To be honest, it was only two years ago on reddit/cfs that I discovered that sporting activities don’t ‘normally’ make you ill, and that all sorts of things I’ve always avoided or tried to overcome don’t actually need to be, (thanks to the many post-Covid accounts, whose remembering is fresh and where the before-and-after contrast is striking)
I can’t be 100 per cent sure; there might be something else going on. I base my opinion on delayed flu-like symptoms and vivid dreams.

@Chris Ponting would a cohort of people who’ve been ill since childhood provide any interesting insights from a genetic point of view?

 

[ScoutB]

Do you mean that the rare variants might dramatically increase the risk of getting ME/CFS, up to the point that you might be virtually guaranteed to get it before turning X years old?

All of the other genes would still be involved in «causing» ME/CFS in the sense that they would still be involved in the disease processes somehow.

Yes, I don't want to put words in Simon's mouth, but roughly I think he was using 'causal' just to emphasize that they could have an effect on ME/CFS risk that's so large it's obvious, even just looking at a few people with and without the variant. It might be that a rare variant could theoretically increase risk enough that it's worth people genetically testing for it.

It's a non-technical use of the word causal. The decodeME variants are still causal in the proper/technical sense of "they came before ME/CFS and combined with other factors to ultimately cause it."

 

[Chris Ponting]

I think I’m one of them. To be honest, it was only two years ago on reddit/cfs that I discovered that sporting activities don’t ‘normally’ make you ill, and that all sorts of things I’ve always avoided or tried to overcome don’t actually need to be, (thanks to the many post-Covid accounts, whose remembering is fresh and where the before-and-after contrast is striking)
I can’t be 100 per cent sure; there might be something else going on. I base my opinion on delayed flu-like symptoms and vivid dreams.

@Chris Ponting would a cohort of people who’ve been ill since childhood provide any interesting insights from a genetic point of view?

Thanks. I once saw a graph implying there are very few people with initial ME/CFS symptom onset before, say, 5 years old. So the cohort might be quite small (so underpowered for this question). Geneticists would be especially interested if anyone with early onset had multiple family members also with pre-adult ME/CFS onset though.

 

[SugarSquared]

Geneticists would be especially interested if anyone with early onset had multiple family members also with pre-adult ME/CFS onset though.

Have you been in contact with the Dr. Nataliya Di Donato and the team at Hanover Medical School who will be investigating the genetics in families with multiple members diagnosed with ME/CFS? It seems their study will be well-equiped to answer this question.

I can't remember if we have a thread for it yet or not, but here is a brief summary from the ME/CFS Research Foundation that gave them a grant:

2. Genetic Determinants of Post-Infectious ME/CFS: a 50-Family Study

Principal investigator: Prof. Dr. Nataliya Di Donato

Project location: Hannover Medical School (MHH)

Research area: Disease mechanisms

Summary: The project looks into families in which several members have been diagnosed with ME/CFS, aiming to identify genetic risk factors for ME/CFS. Identified families will undergo medical examinations, with their genetic information being analysed using state-of-the-art methods. The project aims to provide a better understanding of the biological causes of ME/CFS and to lay the foundations for improved diagnostics, biomarkers and targeted treatment.

More details about the project:
This project addresses an important gap in ME/CFS research by focusing on families in which several members are affected. Such familial clustering suggests that inherited genetic factors may contribute to disease susceptibility. The project will establish a deeply characterised cohort of 50 families with at least two affected members. Participants will undergo standardised clinical, neurological, and neuropsychological assessments, and severely affected individuals will be included through home visits. Blood samples will undergo state-of-the-art long-read whole-genome sequencing (WGS) to identify complex genetic variation, structural variants, repeat expansions, and DNA methylation patterns that may contribute to disease susceptibility. Additional biospecimens will be stored in the Hannover Unified Biobank to enable future studies of immune function and other molecular mechanisms. By combining comprehensive clinical phenotyping with advanced genomic technologies, the project aims to identify genetic susceptibility factors for post-infectious ME/CFS, improve disease stratification, and establish a sustainable resource for future research. Ultimately, the findings are expected to support the development of improved biomarkers, more precise diagnostics, and targeted therapeutic strategies.

 

[justlxsa]

Thanks. I once saw a graph implying there are very few people with initial ME/CFS symptom onset before, say, 5 years old. So the cohort might be quite small (so underpowered for this question). Geneticists would be especially interested if anyone with early onset had multiple family members also with pre-adult ME/CFS onset though.

I’d think so (but that is just a guess based on n=2).
From Nicht Genesen Kids in Germany (~1000 families with ME/CFS or LongCovid or PostVac children), I know that there a minimum of 2 families that have children with early onset (not before 5 though, I think they were both 6 or 7).
Their siblings both have ME/CFS too and are only 3-4 years older. In both cases the onset was 1-2 years apart between both siblings.

Could be more, as I don’t know all 1000

 

[Axel]

Thank you @Chris Ponting and others
That doesn’t seem to be the case in my family.

I think that, in any event, this proportion of young patients is logicly included in the sample Sequence ME and LC and that, if they do happen to carry rare deleterious variants, you’ll find them.

 

[Sean]

Likely to be difficulty in diagnosing accurately in the under 5 year olds, given the current absence of more objective tests.