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I won't speak for others - maybe it would be good to focus in on those. I just like the nervous system angle based on the genetic evidence seeming to provide stronger evidence towards that (MAGMA from DecodeME and the model from Zhang 2025, to be clear).

Oh sorry, I did mischaracterize the quote I posted. I was thinking about this quote while writing that (which to be clear, seems like a somewhat reasonable idea to me):

But with regard to the idea of ME/CFS Science Blog quoted above, where if we suspect ME/CFS is a nervous system disease, and one of the nearest genes is a nervous system gene, then maybe it's worth giving it a little extra weight: [edit: see context below regarding the quote - I was thinking of...

Good question. To restate what's at issue here: if we have a significant locus, and we have no other information, what's the likelihood that the nearest protein-coding gene (NEGR1 in this case) is the pathogenic gene implicated by the significant variant? I realize I rather uncritically...

The lead variant of the locus looks to be close to the threshold (p = 1.19e-7). The locus doesn't overlap the gene, but that's the case for many DecodeME candidate genes.

That plot includes lots of non-coding RNA. This one shows NEGR1 and LRRIQ3 are the closest coding genes to this locus. NEGR1 is interesting because there seems to be growing evidence that it is relevant in depression and anxiety disorders, though it seems like the causal variant is different...

I'll need to read this paper thoroughly, but if I understood previous comments from @LizWorthey, the collection of variants presented is not based on trying to find variants that are found in multiple participants. Each individual was searched for variants indendently, and KCNJ18 turned out to...

Health Rising: 'Precision Medicine Required For ME/CFS? A Deep Genome Dive Uncovers Many Possible Causes'

Responding to a question about this paper from a different thread. It does seem like if someone is sleep-deprived and thus falls asleep faster, one would expect to see impairments in sustained attention tasks. It might be too small a sample, and too much noise due to other causes of impaired...

Maybe you meant to post it in the other thread about ESS, and used the Insert Quote button on the wrong thread, since I see the quote in your post is from a different thread?

Here's one study: Plasma exchange therapy for the post COVID-19 condition: a phase II, double-blind, placebo-controlled, randomized trial (2025, Nature Communications) (Thread)

Good catch. That's very strange and misleading, especially when using the wrong number prominently in the abstract.

What's the reason for pointing this out about MSLT and ESS in this thread, as I only see the abstract describing using the psychomotor vigilance test (PVT) but not those other two? Did you mean to say that objective sleepiness (MSLT) and objective vigilance (PVT) don't reflect the same pathology?

Interesting! I've only read the the first paper so far, but it looks like what they have shown is basically that variants associated with complex traits (GWAS hits) and variants associated with changes in gene expression (eQTL hits) tend to be fundamentally different in several ways. They...

@Chris Ponting I think you might be interested in these other potentially overlapping loci, if you're not already aware of them. It seems like there might end up being a lot of genetic similarity between ME/CFS and pain.

Nice find! Just noting for the thread that this is the study that DecodeME said overlapped at CA10. They didn't look at the other loci because they weren't genome-wide significant. I wanted to compare the other loci, so I downloaded the summary stats for this study from GWAS Catalog, then did...

I think CACNA1E is the gene from DecodeME. Note also this other gene in the same family:

Any chance anyone knows the thread that the original image was discussed on?

The above explanation might have had some hard to understand parts, so I think it might be useful to describe TWAS with a really simple toy example. Hopefully, people can get a feel for what it is, in case we start seeing ME/CFS papers using it. To make it simple, I'll focus on one gene and one...

Now published: Genetic Insights into Circulating Complement Proteins in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Potential Inflammatory Subgroup Abstract Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating multi-system illness with heterogeneity that...