Good question, I'm not sure how correction would work in that case.Would that affect how the corrections for multiple testing is done, and potentially obfuscate leads?
Good question, I'm not sure how correction would work in that case.Would that affect how the corrections for multiple testing is done, and potentially obfuscate leads?
Very good points. It might be more trouble than it's worth if it only controls for a tiny portion of the phenomenon.I think it might be useful if it is possible to create a big cohort that meets those criteria, but ultimately it would only address one or two small facets of "susceptibility."
Still a useful exercise to think about, though! I think it just speaks to the limitations of GWAS (or any big data screening approach, really) and the danger of making runaway conclusions about mechanism solely on the basis of those results.Very good points. It might be more trouble than it's worth if it only controls for a tiny portion of the phenomenon.
Yes, my main fear that prompted the post was the ambiguity of, for example, an HLA allele finding. It might just cause people to get sick more severely and more often, which doesn't really seem that interesting in terms of how to treat ME/CFS if the subsequent disease process has nothing to do with HLA. There are ways that HLA could be central to the disease process, as Jonathan pointed out, but I'm just thinking about how to unravel if that is the case or not.I think it just speaks to the limitations of GWAS (or any big data screening approach, really) and the danger of making runaway conclusions about mechanism solely on the basis of those results.
It’s a good concern to have, and I think ultimately it’ll come down to mechanistic studies to confirm or deny. The aftermath of DecodeME will probably be a series of studies hypothesizing “well these genes suggest XYZ process might be involved, do we see additional evidence of that pathway being relevant? And if so, does targeting that process lead to any symptom improvement?”Yes, my main fear that prompted the post was the ambiguity of, for example, an HLA allele finding. It might just cause people to get sick more severely and more often, which doesn't really seem that interesting in terms of how to treat ME/CFS if the subsequent disease process has nothing to do with HLA. There are ways that HLA could be central to the disease process, as Jonathan pointed out, but I'm just thinking about how to unravel if that is the case or not.
Does getting ME relate to infection severity? I had the impression that it didn'tPractically, if you're just using any and all ME/CFS cases, there's not really any way to control for severity since everyone has had lots of different infections.
I always thought of a GWAS study as being hypothesis generating rather than giving the answer. I think that is how they are more generally seen. So in ME/CFS research this means that if say DECODE comes up with come genes of interest then this could translate to research projects that explore those potential mechanisms. Rather than a conclusion that it is those mechanisms.Still a useful exercise to think about, though! I think it just speaks to the limitations of GWAS (or any big data screening approach, really) and the danger of making runaway conclusions about mechanism solely on the basis of those results.
I'm not sure that it's been studied much. I was mostly just extrapolating based the potential link in long COVID. Though even if severity isn't associated with ME/CFS, it seems likely that frequency of getting infections would be associated. If someone never gets infections, they can't get a post-infectious illness. (Though maybe in these people the same illness eventually starts without the infectious trigger anyway.)Does getting ME relate to infection severity? I had the impression that it didn't
Results: Preliminary analyses indicated that risk factors for non-recovery from PIF included lower physical fitness, female gender, severity of the acute sickness response, and autonomic dysfunction.
It's very much up for debate--I did a deep dive on it about a month ago when I was searching for citations on that claim for a LC publication. There's evidence on both sides to some extent, the main issue is extreme inconsistency in how it's assessed.
For example, the studies I looked at varied on whether or not age was accounted for as a covariate (since age was strongly associated with severe disease to begin with), whether LC was defined by long-term physical and cognitive deficit or simply the persistence of one or more symptoms after infection, and whether there was enough data from non-hospitalized LC cases to accurately judge prevalence from mild infection.
As one example, the research team I was part of put out this study showing no correlation with severity amongst hospitalized patients. Granted, all were hospitalized, so it is skewed in that way. Though we did have a good number of mild cases that didn't exhibit high respiratory distress and were discharged after just a few days with no or minimal treatments.
I'm not sure that it's been studied much.
Though even if severity isn't associated with ME/CFS, it seems likely that frequency of getting infections would be associated.
Also people report getting ME after being vaccinated which is a weak infection (i.e. in causes the immune system to work). I had assumed that there maybe a state where if in that state when the immune system in activated more than normal it could cause ME.I'm not convinced severity of infection is really necessary as a factor, and it would be impractical to measure frequency. We probably aren't aware of some of the infections we've had because our immune systems dealt with them silently.
Evidence so far suggests it does not at all. The lie is simply kept alive because it has been asserted for so long, medicine lacks the tools to assess it reliably, and it's too convenient in order to suppress the whole issue. In the early days of the ideology, it was simply asserted, as it provided a convenient excuse for deconditioning.Does getting ME relate to infection severity? I had the impression that it didn't
As you say we need to be careful with long covid as some have ME like disease but it seems to cover a whole range of other long term issues.There is a slight uptick in LC rates when the threshold of severity is defined by hospitalization, but it seems to be more about the kind of tissue and organ damage, such as from pneumonia, that isn't found in the chronic illness category, and evidence so far mostly shows that those commonly recover. I don't remember any good studies that compared PEM prevalence, but it's not as if good studies are in abundance here.
Or non-symptomatic? Or would that be on a spectrum of severity?If someone never gets infections, they can't get a post-infectious illness. (Though maybe in these people the same illness eventually starts without the infectious trigger anyway.)
I think I’ve mentioned mine was possibly triggered after ending up in hospital after a kidney infection wasn’t treated properly and went bad. I do seem to be a rarity but the descriptions of post-sepsis syndrome and ME/CFS do seem similar so I’ve often wondered if there’s something to learn there.Maybe because it hasn't really emerged as a factor in people's descriptions of onset? If you developed ME/CFS after needing hospital treatment for an infection, you'd usually say so—unplanned hospitalisation is a significant event.