Genetic Predisposition for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Pilot Study 2019 Perez Nathanson Klimas et al

[wigglethemouse]

How come there is so much difference in OpenSNP ?

Regarding CYP2D6 : I have rs28371725, Risk is T with MAF 0.06% :

It's acutally very similar. A % sign was added after MAF=0.06 instead of quoting as MAF=0.06 = 6%
From dbSNP (expand the + sign to see 1000 genomes)
T=0.063 (318/5008, 1000G)

 

[mariovitali]

It's acutally very similar. A % sign was added after MAF=0.06 instead of quoting as MAF=0.06 = 6%
From dbSNP (expand the + sign to see 1000 genomes)
T=0.063 (318/5008, 1000G)

Ah yes i see what you mean,I shouldn’t have added the percentage sign after 0.06 or just write 6%.

So the MAF is 6%. My understanding based on MAF=6% of 1000 Genomes is that we would expect to find around 6% of this frequency in the population for this SNP and in my cohort i find it almost 3 times more (16.9%). Should have i used the frequency of OpenSNP to make comparisons?


Regarding GPBAR1 : Here is the snapshot from the Network shown at my tweet. Under the oval annotation we find FGF21 (which means that there is an association of GPBAR1 with FGF21) :








This is a snapshot from Mark Davis's talk at the NIH Conference, FGF21 is there :

 

[wigglethemouse]

I am curious to see if they identified a gene called SERPINE1 / PAI1 which is part of extracellular matrix organisation.

What is your interest in SERPINE1 @mariovitali ? According to this mutations can cause mild to moderate bleeding.....
https://ghr.nlm.nih.gov/gene/SERPINE1

 

[wigglethemouse]

I was expecting more discussion here on this paper than has happened - very very very poor analysis of data in this paper by the researchers.
* mixing of different v4 vs v5 data but including both in frequency count even if one type has no data.
* known miscalls on 23andMe data are highlighted as key important items
* Uses Kaviar frequency even where other databases show a massive difference in population frequency
* Obvious data errors that can be picked out by the eye. You don't need to be a statistician or genetic researcher to see this
* Lack of description in the paper on method used to calculate MECFS frequency values.
* I got @mariovitali excited before I realised the items he is interested in have bullshit data (GPBAR1 and CYP2D6)

More discussion of errors on PR
https://forums.phoenixrising.me/thr...lot-study-perez-et-al-2019.76400/post-2206507

Here is the supplemental data for anyone interested.
https://www.frontiersin.org/articles/10.3389/fped.2019.00206/full#supplementary-material

What are your thoughts? Should the paper be retracted?

 

[mariovitali]

@wigglethemouse

-Thank you for the work you are doing. One obvious first question is whether this paper was reviewed as it should. Since so many issues exist it is obvious that the paper should be retracted although i do not know what happens under these cicumstances.

-We find that most likely we have subgroup types of PwME. I strongly believe that a percentage of PwME have an underlying problem that affects negatively liver function (e.g @Ravn - hemochromatosis) and also the system suggests several targets that include hepatotoxicity risk (including CYP2D6).

I suggest a read on the following :

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5713322/

-Regarding SERPINE1/PAI1 : The system i believe gives this suggestion due to a *possible* protective of this gene to hepatic function but of course i do not have the knowledge to give hypotheses as to why this is identified as a target :


https://www.physiology.org/doi/full/10.1152/ajpgi.00107.2009

EDIT : Please disregard attached file

 

[Trish]

I was expecting more discussion here on this paper than has happened - very very very poor analysis of data in this paper by the researchers.

Hi @wigglethemouse. I'd love to be able to join in with analysing data like this, but I simply don't have the energy or knowledge to make any useful contribution. I suspect most of us here are in that situation. Thanks for your efforts on it. Have you thought of contacting the researchers with your concerns?

 

[Ravn]

-We find that most likely we have subgroup types of PwME. I strongly believe that a percentage of PwME have an underlying problem that affects negatively liver function (e.g @Ravn - hemochromatosis)

Just to be clear, any liver involvement in my case is speculation on @mariovitali's part. It is correct that I have haemochromatosis but it was caught early enough that my iron overload never reached the sort of levels where liver damage is likely. My standard liver function tests are always fine. I don't have access to any fancier sort of tests so can't say 100% that I don't have any liver damage at all - but I definitely don't have any known issues there.

Potential problems with dysregulated iron metabolism have shown up in a couple of ME studies recently but they're pointing towards different mechanisms not specifically involving the liver. I remain interested but agnostic regarding any link, via whatever mechanism, liver or otherwise, there may or may not be between my haemochromatosis and my ME.

Not wanting to discourage you from your research at all @mariovitali, for all I know you may turn out to be right. I just wanted clarify that I don't have any known liver problems in case anyone got that false idea.

 

[mariovitali]

Just to be clear, any liver involvement in my case is speculation on @mariovitali's part. It is correct that I have haemochromatosis but it was caught early enough that my iron overload never reached the sort of levels where liver damage is likely. My standard liver function tests are always fine. I don't have access to any fancier sort of tests so can't say 100% that I don't have any liver damage at all - but I definitely don't have any known issues there.

Potential problems with dysregulated iron metabolism have shown up in a couple of ME studies recently but they're pointing towards different mechanisms not specifically involving the liver. I remain interested but agnostic regarding any link, via whatever mechanism, liver or otherwise, there may or may not be between my haemochromatosis and my ME.

Not wanting to discourage you from your research at all @mariovitali, for all I know you may turn out to be right. I just wanted clarify that I don't have any known liver problems in case anyone got that false idea.

No problem at all @Ravn. I do understand that you cannot get into any fancy testing. Some ME patients were found with liver fibrosis but we must explore these findings on a greater scale. Other ME patients did not have fibrosis. Others had elevated total bile acids, a test which has not been performed in ME patients in any study (to the best of my knowledge).

We must keep in mind that normal liver enzymes cannot rule out liver disease.

EDIT : Reading again my message mentioning @Ravn , it does appear that i am implying that he has liver disease. I would like to say that i did not have any intention to imply such message

 

[wigglethemouse]

Hi @wigglethemouse. I'd love to be able to join in with analysing data like this, but I simply don't have the energy or knowledge to make any useful contribution. I suspect most of us here are in that situation. Thanks for your efforts on it. Have you thought of contacting the researchers with your concerns?

Thanks for the suggestion @Trish. I did get around to sending an email to Travis Craddock around the time of his Solve ME/CFS talk highlighting some of the awful mistakes in this paper. I didn't even get the decency of an acknowledgement. Very disappointed.