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Most of this thread is way over my head, but I thought I'd comment on this approach (not necessarily this paper from the team), which was much discussed at the time. The study had been years in the making, and I found it a bit disappointing as a model. they used the shoulder fatigue scale to...

Thanks. There were no HLA/MHC gene flagged as likely candidates in DecodeME. Excluding HLA, do you have any feel for what percentage of human genes are immune ones?

Could you clarify that, please? The way it was explained to me, magma looks at the set of 13 genes only, and compares them with other genes. It doesn't look at any other ME/CFS genes. Are you saying that's not the case? I may have misunderstood you or what was explained to me originally.

It sounds like an interesting thing to do. But he thought anyone commits resources to do any experiment, it would be useful to have the planned analysis narrow down the like candidates. Which would also presume they have a big impact on the credible hypothesis. Maybe it's because I've been ill...

Maybe a better way is to estimate the number of immune genes. I found one at about 1600 genes . https://pubmed.ncbi.nlm.nih.gov/15789058/Let's say 2000 – or about 10% of all human genes. As far as I can see, quite a lot more than 10% of candidate genes linked to the DecodeME genetic signals...

On the face of it, the magma analysis is the stand out finding, and highlights stuff going on in the brain. However, my understanding is that magma is not as robust as the EQTL analysis, though I think that's probably debatable. I think that's the reason why the authors is placed less...

I'm not sure that is the case. The first thing they look for is the genetic signal, then they look to see what was captured by that genetic signal. I think that was mainly protein coding genes. I had a feeling there was at least one RNA species. I don't know if that showed up in the...

I remember talking to Chris Ponting this study years ago, and the possibility of a study focused on immune genes. These are much more affordable. His comment was that these kind of targeted genetic studies used to be very popular, but have a poor track record on replication. And that's when...

Possibly Veronica's finest so far. Yes, heartbreaking.

Good analogy I'm pretty sure genes identified by GWAS make identical proteins, and variants instead alter gene regulation, usually not by very much. That's one reason why effect sizes are small. So it may be that the dam is stronger because a bit more of this protein is produced. But the...

How sure of this can we be at this stage? The two specific bits of evidence I'm aware of, the most relevant CA 10 for pain, which is directly affects neuron. However, there's also a microglial gene. Microglial are glia not neurons. Then there are the 13 tissues where candidate ME/CFS genes are...

I would say the gold standard is diagnosis by expert clinicians. We know from a couple of studies that half of GP diagnoses are wrong – and almost all cases because that had been other, undiagnosed diseases (mostly biomedical, but also psychological) that explain the symptoms. I suspect the...

Thanks, both. That have been my understanding, but I wanted to check it. ADDED and I think this is an important message to convey to people who understandably wonder what the relevance of this big genetic study is to them when many won't have the relevant genetic differences, and heritability...

(This as the answer to the question about how can small genetic differences between cases controls produce valuable information ) Is it also true that somebody who doesn't have a relevant genetic difference in a particular gene can benefit from any such drug targeting the biology behind the...

I suspect it is it's practical rather than strategic. I believe sex chromosomes have to be analysed separately in all GWAS . So it makes sense to do all the autodomed (non--sex chromosomes) first. The wind we also have six chromosome data – which is one of the things they flagged up – we'll...

I know there was extensive QC, and your and @forestglip 's Manhattan plots showed how important they were (there would have been lots more exciting results without QC, no doubt lots of blind alleys). Maybe @Andy can comment?

Interesting. This came out in 2023, and I was unsurprised then, and I don't think it drew any comment from PwME. I'm sure I've seen similarly high figures in other large patient surveys. Can anyone point to other large symptom surveys? Assuming this is right, the surveys are more likely to be...

Belated thanks for creating this audio– must be very helpful for some people

It hasn't been done yet, though something Chris said on the video makes me think they are considering it. A big problem is that, while they can pick up people with a recorded diagnosis, we know many of those are wrong. And there's no questionnaire data to qualify. The paper refers to the three...

Lots of conditions have chronic pain, so I'm not sure there would be enough people with undiagnosed ME/CFS to make a difference. Particularly as those most likely to be under diagnosed have non- white ethnicities. And they are under diagnosed with most things (the situation is more extreme...