Lots of good questions. I’ve been thinking and I’m not sure. But I’d say things haven’t been moving forward in clinical care because there has not been an alternative. Patients, doctors, charities have and still do want to ‘do something’ and the only people offering ‘something’ have been the BPS...
I agree with much of what you say @Sasha and I may have misunderstood parts of your proposal. You’re absolutely right that we need medics involved somehow. It’s perhaps easier in science because we have good examples now. The problem as we’ve discussed elsewhere is there are no good examples of...
Some more thoughts on the local MAGMA results above. The difference in the gene based analysis is worth looking at too. It would be useful to understand why (discussing with @forestglip we wondered if it was the difference in SNP conversion methods and assemblies used, or perhaps the reference...
I think the off ramp is as described, a path of least resistance for people based upon new evidence and solid science. Public displays of damascene conversions are unlikely and probably not helpful.
Having prominent and respected people involved is part of the answer to me. As it looks as if is...
Yes looks that’s probably the case. The eligibility criteria seem to make that clear and I can see them being able to use the data in a publicly accessible tool like FUMA but not being able to share it. A shame as it limits our ability to remove variables that may be causing differences in...
All really good points, and having prominent people show a path for others to follow could be useful. Having some medical big guns on side could be really useful as you suggest.
How it is done is important. Saying we need to improve care, look for treatments, invest in research to build upon...
I’ve been thinking more about this and it would be really useful if we could get hold of that UKB reference data to use with standalone MAGMA and see if it helps align our results. I wonder if it’s worth asking them?
It’s not here
https://cncr.nl/research/magma/
It’s mentioned here but not...
You’re right it’s something important to be aware of. And the suggestion @Sasha makes of having prominent figures open the door or show a path for others to follow may be useful or perhaps here are other ways they can help or influence things.
I’m just far less convinced that there is a...
I hadn’t noticed but then again only just looked into who he was when you flagged it. Looks like a very handy person to have as part of the team!
Really interesting, so it’s less a case of the rare variants completely changing the picture or being independent of the common variants found, but...
It's not though. The baseline assumption for the majority of people is that they don't know or even care about ME/CFS. The world we are living in is one in which ME/CFS has been ignored, it is that (and yes for some their positions) which has allowed a small group of people whose minds we will...
It looks from the paper as if the used a tool called coloc described in this paper: Bayesian test for colocalisation between pairs of genetic association studies using summary statistics. Which I think does just compare individual gwas studies via their summary statistics.
But one interesting...
There is one result from gene-set analysis I thought may be worth looking into
On the group DecodeME_gwas1_infectious_onset the top result was this GSE2770_UNTREATED_VS_TGFB_AND_IL12_TREATED_ACT_CD4_TCELL_48H_UP (link to the MSigDB page for this set)
This is a set which comprises "Genes...
Identification of novel genes regulated by IL-12, IL-4, or TGF-beta during the early polarization of CD4+ lymphocytes
Riikka Lund, Tero Aittokallio, Olli Nevalainen, Riitta Lahesmaa
Abstract
Th1 and Th2 cells arise from a common precursor cell in response to triggering through the TCR and...
Some results from running MAGMA locally.
Both gene based and gene-set analysis using the above method on each of the DecodeME GWAS subgroups against the full Molecular Signatures Database Human Collections release 2025.1 (MSigDB 2025.1.Hs).
Please bear in mind this method differs from the way...
Something I’ve only really started to appreciate going through this process is quite what is being done and quite how clever and meaningful it is… and how those dismissing it are showing their own ignorance and how their ideas about genetics are decades out of date.
I’m still pretty ignorant...
Looks interesting! Not sure what sort of computing power it would require…
It does use a python library for doing liftover though, which looks interesting!
https://pypi.org/project/pyliftover/
As mentioned above, something @forestglip and I have been working on recently is running MAGMA locally on the DecodeME summary statistics.
I wouldn’t necessarily recommend anyone do this or follow these instructions. There may be things wrong with this method and it seems to end up with only...
Thanks @Chris Ponting I look forward to seeing what more there is to come and echo @Hoopoe in thanking you and the rest of the team, for all you’ve done so far. The more I’m learning the more possibilities and scope there seems to be, exciting times!
Really useful answers in general but also in...
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