Is ME more heritable on the mother's side?

Are mothers with ME more likely to have children with ME than fathers with ME are? I've always wondered about this, partly because it is true in my own family, and have seen others suggest it might be true (most recently Fereshteh Jahaniani in the NIH genetics webinar), but I can't seem to find any solid data on the question. Has anyone seen anything along these lines?

It's difficult to separate overall higher female prevalence from higher maternal heritability without data. I've certainly anecdotally heard of a lot more families with maternal inheritance than paternal, but you would expect that to some degree (and there are definitely some families with paternal inheritance).

There is Mirrored Symptoms in Mother and Child With Chronic Fatigue Syndrome, which found 9 mothers and 0 fathers of teens with CFS also had CFS per CDC definition, but that's questionnaire-based and definitely BPS, so I'm not sure it means much.
Evidence for a heritable predisposition to Chronic Fatigue Syndrome (the Utah study) seems like it would be able to answer this question, but it does not.

Mitochondrial DNA variants correlate with symptoms in myalgic encephalomyelitis/chronic fatigue syndrome seems like a fairly solid effort to sequence mtDNA that didn't find anything, which certainly makes this less likely.

Maybe this question would be amenable to a little research project, if it hasn't been answered.

 

If there is anything autoimmune going on in ME then that is most likely to be coming from the mother rather than the father.

Source : https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(05)74535-9/fulltext

 

My family have both maternal and paternal inheritance - pedigree below for interest. I've put my mother as a question mark because she clearly developed PEM and disabling orthostatic intolerance after her fourth booster, though was fine with all prior vaccinations and has never had Covid. She's in her late 80s so would have been unlikely to ever be given a diagnosis of ME/CFS over "old age". However, she seems to have recovered after about 10 months and is back to walking freely around the city and is considered to be in "rude good health" (a reversal that I don't think is a well described feature of old age).

 

The science underlying this is way beyond my very limited knowledge - so I'm probably missing the point ---

Vicky Whittemore, in the NIH genetics webinar, and the rest of the panel, seemed to be very positive re the need to do a large GWAS [including sequence mtDNA (to find rare variants?)]. Maureen Hanson, one of the authors of a study you refer to*, raised the question around 1 hr 57 mins from the start of the webinar**.

Recommendations, re research to fund, arising from these webinars etc, are due to be made in May 2024 - so we'll know then whether a large GWAS (including sequence mtDNA?) is recommended (I'm hopeful) then there's the question of what gets funded & when--- seems to take a long time!

*https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-016-0771-6
**

https://www.youtube.com/watch?v=3Sv93qHF0WQ

 

As far as I know we don't have any good data.

There are two different questions though. One is whether PWME are more likely to have a mother or a father with ME and the second is whether the link is genetic or some other factor - of which there are several possibilities.

Although women have more autoimmunity that does not mean that they are more likely to be the source of autoimmunity in a child. The risk factor comes with having two X chromosomes and that is not inherited - it is a matter of chance!!

The McPhee family I think buck the trend if there is one.

The main mechanisms for predominant inheritance from mother are mitochondrial DNA problems, which look unlikely to be a factor in ME, and X-lnked genes producing an X-linked recessive picture. Again, that seems unlikely on its own but it might just about contribute.

DecodeME may tell us that although there definitely appears to be familial clustering that it is unlikely to be due to genetic inheritance. That would raise a major puzzle but it is perfectly possible. Disease causation is very complicated.

 

Nailed it, problem is that post rituximab there's no good evidence supporting autoantibodies -- is there another sort of "autoimmunity"?

 

With GWAS you can trace back mitochondrial lines further than mothers .
Traits are interesting too and inherited.

My maternal aunt and my daughter both have ME . My daughter is moderate / severe. My aunt is severe .

My daughter has always been said to be a mini version of her great aunt .
Sense of humour, sarcastic wit, favourite colours , food likes, tolerating no nonsense and both very private people ......

I'm looking forward to the combination of AI and genetics in research and hoping we may get some answers faster .
ETA great aunt not aunt