Familial coaggregation and shared familiality of functional and internalizing disorders in the Lifelines cohort, 2025, Bos et al

That’s really interesting, have you or any of your family members done whole genome sequencing? It would probably be a crap shoot if you don’t have a good geneticist that could interpret a result that’s not already well associated with a disease, but could turn up something useful.

 

Do you really think there’s a chance something useful could be found? Because it’s definitely not like we all had the same illness.
I’m severe Me/cfs, my mum something that looks like mild me/cfs plus hashimoto’s, my grandma Ankylosing spondylitis and disabling migraines, and great grandma I think it was a chronic illness with migraines and fatigue but my memories super fuzzy it’s not like I ever met her.

 

I think in situations like what you describe, it could be one allele that drives dysfunction in one part of the immune system, perhaps in some regulatory mechanism, but the particular “flavor” of how it manifests would be influenced by environmental factors, the other half of your genetics, etc.

If you haven’t already had it done, it might not be worth it as it can be expensive and would not really be useful for any diagnostic purposes as none of those diseases follow Mendelian inheritance. It would be more of an interesting bit of information in that case

 

I definitely relate with what you say about Hashimoto’s though because my mum has it

 

I suspect the ME/CFS prevalence in this cohort was largely based on the CDC symptom inventory. This Wiki for the Lifelines project provides some more information:
https://wiki.lifelines.nl/doku.php?id=cfs_diagnostic_score
https://wiki.lifelines.nl/doku.php?id=fatigue_cdc

 

Just putting the data here so we know what we discuss: from supplementary table 4:

Familial coaggregation for ME/CFS amongst relatives expressed in:
λR (95 % CI) | f2 (95 % CI):

First-degree:
2.23 (1.89-2.58) | 0.43 (0.34-0.51)

Second-degree:
1.17 (0.69-1.66) | 0.15 (-0.24-0.54)

 

1. There are serious doubts about accuracy of diagnosis, well rooted out here:

So it's is basically chronic faitgue plus at least 4 out of 8 largely generic CDC/Fukuda symptoms, with no mandatory pem, whose assessment in any case is unclear. And no attempt to diagnose alternative causes of fatigue, which is the hardest and most important aspect of diagnosis

As @ME/CFS Skeptic points out, the 4%+ prevalance adds to the doubt. This looks like a diagnosis of CF/poor health. It isn't surprising they find a substantial overlap with other disorders, probably similarly poorly diagnosed.

It looks like a big fuzzy mess inevitably overlaps internally, but probably with little chance of finding out anything meaningful.

Looking at it another way:
DecodeME's grant application cited the Utah registry study that found an ME/CFS heritability of (I think) 0.12; respectable, but still pretty low on a 0-1 scale. That figure could include familial environmental factors, including behaviour, i.e. an unknown genetic contribution.

DecodeME itself will calculate genetic-only heritability. If that is similar to the Utah study, it will suggest that environmental factors are relatively low. Of course, this study is claiming that genetics is important.

But what are those shared genetic influences? At that stage, what would matter is which genes are implicated - what biology? Maybe it points to biological, not psychosocial factors. I'm not aware of any GWAS for, say, FM or IBS, but if there are, I expect Chris and co. will be looking at them, either in the main paper or later. At this point, we would have good data to debate the overlap between FD/ID and ME/CFS. Currently, we seem only to have unsafe data and a lot of speculation.

Wouldn't it be nice to have some good data and move on to discussing science, not pile up papers that sort of support the views of authors but are full of holes and take us nowhere?

Well, that's my bit of frustration coming out!

 

The lifelines cohort is very valuable. I wonder if they could retrospectively try to make the definition of ME/CFS more stringent to get something below 1% prevalence.

They could for example make the CDC symptom inventory items for PEM, unrefreshing sleep and concentration problems mandatory. Perhaps they could use a required threshold for the CIS-scales for fatigue and concentration. I think they also asked about self-reported ME/CFS diagnosis, so they could also use or add that to make their definition more specific..
https://wiki.lifelines.nl/doku.php?id=fatigue_general

 

That would be a good move, Especially if they do have aggression about about self-reported. Do you know what the exact question is about PEM?

 

make “unrefreshing sleep and concentration problems mandatory”

the characteristic sleep problem of ME is reversal of the day and night rhythm and I don’t suffer from unrefreshing sleep. You don’t need to have concentration problems and I certainly don’t have them. I have bad cognitive problems but that’s totally different and an abnormally delayed recovery after doing trivial things with my brain. That has got nothing to do with concentration problems. And as you know I’m bedridden with very severe ME.

Moreover labelling ME a functional disorder by the psychosomatic professor when she concluded that it is a bad physical disease when she was part of the national health council, is just a form very bad medicine. Even more so because she doesn’t present any evidence for that assumption.