Is ME more heritable on the mother's side?

LarsSG

LarsSG

Senior Member (Voting Rights)
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's something with the mitochondria, then maybe? And paternal genes could contribute by changing compensatory factors? Again somewhere cohort studies with -omics data could have been used if only ME/CFS status was asked about or there was a patient registry one could apply to for selection purposes :(
 
If there is anything autoimmune going on in ME then that is most likely to be coming from the mother rather than the father.
Why are women are so much more likely than men to develop autoimmune diseases? Women are two to three times more likely to develop multiple sclerosis (MS) and rheumatoid arthritis (RA) and make up 75% of cases of myasthenia gravis. In fact, in the USA, of the 8·5 million people with autoimmune diseases, 80% are women.
Click to expand...

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).

SNTG Pedigree.jpg
 
Including myself I know of three members of my extended family with diagnosed ME, only one has a parent with ME (and I'm not related to said parent). There could be more though, the one mother-child dyad I know of is a sixth cousin and I found out by chance. I am pretty confident I would know about at least regular cousins developing ME seeing my mother gets questions about other health conditions in the family and if someone developed ME I'd think she would be asked about my health as well.

Then again with how this illness is being perceived and people discouraged from seeking patient communities to avoid becoming stuck in the sick role who knows :banghead:
 
In my family those I'm aware of are possibly my father, definitely myself and my daughter, and now my niece (sister's daughter) has long covid.

[I say possibly about my father because he had what was described as a recurring virus by our GP, that started in the 1930's when he was in his 20's with several years being debilitated following a post op. infection. Each time it recurred in later years the treatment that returned him to good health was complete rest from any physical or mental activity until he felt fully well again. When I was diagnosed with ME, he said looking back that's what he thought he'd had.]
 
LarsSG said:
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.
Click to expand...

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
**
 
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.
 
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
 
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