ME/CFS Science Blog
Senior Member (Voting Rights)
Can you tell which one?
Preprint Initial findings from the DecodeME genome-wide association study of myalgic encephalomyelitis/chronic fatigue syndrome, 2025, DecodeMe Collaboration
Jonathan Edwards
Senior Member (Voting Rights)
They are interested in CA10 in the first instance because they come from a pain background.
neophyte32
Senior Member (Voting Rights)
Excuse me, I'm a novice. Chagpt tells me it's a gene expressed in the brain: neuronal signaling, synaptic plasticity, cerebral connectivity, and the autonomic nervous system. Why do you think he's focusing on this particular gene? What might he discover? Does this fit with your theory? Thanks
Yann04
Senior Member (Voting Rights)
I think it’s the only gene we’re decently confident was a decode ME hit. (The other ones we have a hit that could be one of multiple genes).
Also, the same gene/locus was already found in chronic pain, so it makes sense for pain researchers to look at.
The replication in a past study of a somewhat similar condition also makes it less likely that this is a false positive finding.
Jonathan Edwards
Senior Member (Voting Rights)
Right.
Also the high resolution pattern of gene linkages looks as if there may be a specific piece of DNA to focus in on that may control neural signals, including pain. It may not be brain. It may be further down the nervous system. I cannot really give more detail but the DecodeME finding seemed to make sense to my colleagues.
Also the high resolution pattern of gene linkages looks as if there may be a specific piece of DNA to focus in on that may control neural signals, including pain. It may not be brain. It may be further down the nervous system. I cannot really give more detail but the DecodeME finding seemed to make sense to my colleagues.
ElephantNerd
Established Member (Voting Rights)
@Jonathan Edwards Thank you for sharing what you are allowed to share! Totally understand that you can't share certain aspects. I really needed some hope today that progress is being made, so I appreciate you taking the time and effort to share what news you can with us.
Jonathan Edwards
Senior Member (Voting Rights)
Maybe more to do with fibres that bring noxious signals from muscles but I forget the detail. There is a huge amount of detail known about these genes' products in nerve cells now. It is a question of joining all the dots I think.
You've made my day
This is exciting..
Will they use the DecodeME dataset, or gather new patient samples or how does it work?
Jonathan Edwards
Senior Member (Voting Rights)
I cannot give details but this is looking at the basic gene biology to try to figure out what the link to pain and ME/CF might mean.
AliceLily
Senior Member (Voting Rights)
This is really getting interesting and I have been thinking more on this this morning.
I do think this is a strong lead and has quite a heavy bearing on what I think caused my vulnerability to getting ME. I had a significant reaction to a medication at 20 years of age that left me with life-long localized pain and changed homeostasis. Ten years later I got ME via a nasty cold. This early reaction would tie into my ME and finally make sense of how I got ME. I guess we will see. I'm very pleased we are going in this direction and I think something will come of this. Early days though I know.
If anyone wants to learn more about what happened to me when I was 20 I wrote about it in my introduction years ago. I should forewarn that there is a lot of 'TMI' in my introduction, but I felt I had to put it all out there in case it was helpful in finding answers or any clues.
I do think this is a strong lead and has quite a heavy bearing on what I think caused my vulnerability to getting ME. I had a significant reaction to a medication at 20 years of age that left me with life-long localized pain and changed homeostasis. Ten years later I got ME via a nasty cold. This early reaction would tie into my ME and finally make sense of how I got ME. I guess we will see. I'm very pleased we are going in this direction and I think something will come of this. Early days though I know.
If anyone wants to learn more about what happened to me when I was 20 I wrote about it in my introduction years ago. I should forewarn that there is a lot of 'TMI' in my introduction, but I felt I had to put it all out there in case it was helpful in finding answers or any clues.
Simon M
Senior Member (Voting Rights)
It's out there somewhere – not definitely published, but try this paper (1st 17 K questionnaireresponders )
Typing myalgic encephalomyelitis by infection at onset: A DecodeME study - PubMed
DecodeME participants differ in symptoms, comorbid conditions and/or illness severity when stratified by their sex-at-birth and/or infection around the time of ME/CFS onset.
pubmed.ncbi.nlm.nih.gov
Evergreen
Senior Member (Voting Rights)
Fantastic. Thanks so much for sharing this.
Evergreen
Senior Member (Voting Rights)
To add the personal bit I left out of previous post: I am in so much pain at the moment that knowing that UCL geneticists are doing this is so heartening. It's the kind of tidbit that keeps me going.
Andy
Senior Member (Voting rights)
Unlike Simon, I'm afraid I suspect that this information hasn't been shared anywhere. I have asked about it internally but may not get it until the New Year now.
For members that are interested in exploring the data from DecodeME, such as to see if certain genes are near significant loci, here is a link to the summary stats on LocusZoom: https://my.locuszoom.org/gwas/894183/
I wasn't sure if I could share it publicly, but Chris Ponting kindly pointed out that the summary stats are released under a CC-By Attribution 4.0 International license, so sharing is allowed.
As an example of how to use LocusZoom to look at a gene:
I wasn't sure if I could share it publicly, but Chris Ponting kindly pointed out that the summary stats are released under a CC-By Attribution 4.0 International license, so sharing is allowed.
As an example of how to use LocusZoom to look at a gene:
- Find the location of a gene of interest. One way is to go the GeneCards page for a gene, scroll down to the section that says "Genomic Locations for ... Latest assembly", and copy the location which looks like this: 'chr6:31,575,565-31,578,336'
- Click the link that says "region page" on the LocusZoom page above. Paste the gene location you copied into the search box and press Enter, and it'll take you to the gene.
- You can zoom in or out by pressing Shift while 'scrolling' (e.g. drag two fingers on laptop touch pad or spin wheel on mouse).
Download
The script makes a file called gwas_1_sorted.txt.gz, which you would upload to LocusZoom. These are the options I set while uploading:
gwas_1.regenie.gz and gwas_qced.var.gz from OSF, run this code in a terminal in the same folder as the files to make a file suitable for LocusZoom, then upload to LocusZoom and set options as indicated in screenshots.
Bash:
# Filters to only QCed variants, removes non-needed columns, then sorts. Deletes intermediate files at the end.
summary_stats_file='./gwas_1.regenie.gz'
qced_var_file='./gwas_qced.var.gz'
awk 'FNR==NR {if (FNR>1) ids[$1]++; next} FNR==1 || ($3 in ids)' <(zcat "$qced_var_file") <(zcat "$summary_stats_file") > gwas_1_filtered.txt
awk 'BEGIN { OFS = "\t" } {print $1, $2, $4, $5, $6, $13, $14, $16}' gwas_1_filtered.txt > gwas_1_minimal.txt
awk 'NR==1; NR>1 {print $0 | "sort -k1,1n -k2,2n"}' gwas_1_minimal.txt | gzip > gwas_1_sorted.txt.gz
rm gwas_1_filtered.txt gwas_1_minimal.txtThe script makes a file called gwas_1_sorted.txt.gz, which you would upload to LocusZoom. These are the options I set while uploading:
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