Yes, that was the point I was trying to make: it's diagnosis by a heatlhcare professional plus meeting IOM/CCC criteria (assessed by symptoms, inc PEM).
Yes, and it sounds very plausible, though the reality might not have backed that up.
If all these arguments are right, I think you would expect to find a lot of common findings between chronic illness GWAS, and I don' think that is the case (though I think there is some evidence for genetic links to research participation etc).. Also, GWAS findings I'm aware of often tie in with what is already known biologically. E.g. for migraine and RA. And arguable ME/CFS, where findings pointing to immunological and neurological issues are hardly a surprise. Not least the link to infection in particular.
I think the paper explains that these are instead chosen by proximity to the lead variant. Not all genes have eQTL data, or not for all relevant tissues, and it may be that gene expression is only affected under certain circumstance - e.g. energetic demand in ME/CFS. I believe this is a thing on other illnesses too.
Iirc they are actually planning a GWAS with Lipkins lab
Norway is definitely too small on its own. 5.5M gives only 22k patients with 0.4 % prevalence. But on the other hand, the MEA has 7k members, so you’d probably be able to recruit quite a lot of people to a GWAS with a home saliva kit.
If it were mail in home saliva kit like Decode is that a problem?
It's a risk though. There might only have been significant hits just on the cusp of the threshold with the full sample. Reducing the sample size could lead to losing those findings. It might be better to put all the power possible in it while we've got it, and let the replication happen later.
Not sure, was thinking there might be a higher risk of selection bias and not getting a representative sample of the ME/CFS population.
Personally I believe the argument can be made the other way, that mail in sampling helps give a better representative sample by allowing more severely affected patients to take part.
I completely see your point, but at the same time I think one can similarly argue that the genes picked up here aren't that much more different in nature to the genes picked out in the FND study which was my main motivation for asking the question in the first place, where that exact argument seems to have been accepted. At the same time I suppose it's quite reasonable to expect that you might have some additional complexity from confounders not being uniformly distributed amongst (chronic) illnesses (I'm not sure you'd necessarily even want to focus on chronic illnesses given that the intramural study seems to have indicated that there might be people diagnosed with ME/CFS that might have a wide array of conditions), which I think is to be expected, combined with the fact that ME/CFS is in pratice not diagnosed according to criteria and ruling out other causes but according to the preference of (rather) few doctors (but my layman let's me think that such factors might play more of a role in something like Lifelines where somebody might "just be part of a cohort", rather that than in DecodeME where people wanted to specificially be part of one study and where recruitment to a large extent worked through those place where we hang out together on the internet.)
Should it not be fairly easy to look at a comparable to the DecodME cohort (there's very few but I think some smaller ones like some of the cohorts used in the Zhang study seem to meet that description) and do exactly that?
Maybe the biggest advantage of ME/CFS research being decades behind is that genetic research is now cheap and robust!
Yes.
Would that only be if they weren't analysing everything so could have a lower probability threshold?
You got it. If they are hypothesizing about specific genes, they only have to adjust the p-value threshold for as many of these that they are interested in.