DecodeME - UK ME/CFS DNA study underway

[Barry]

So I was just speaking to my partner who; is lovely but also goes through life with a much more cynical / “pessimistic” attitude than me, (opposites in ways!), in the sense that by doing that, he doesn’t get disappointed all the time and feel sad - as he says, expect nothing and then you won’t be sad. Which I totally understand especially if life is difficult.

Well, in his usual manner, he said “better not to be too excited just yet because what if it doesn’t show something, and then you might get too sad” And I got a bit deflated. Was wondering if anyone here could perhaps provide insight (ie reassure me... lol), that the study most likely show something... do we have preliminary results that show there likely is some sort of genetic signal in ME, already?

Firstly, I am not at all qualified medically or scientifically, so this is purely my own uneducated thoughts.

I would guess that if there really is a genetic predisposition to having ME/CFS, then there might be a good chance this study might identify it. If there isn't then of course there would be nothing to find. What I don't know is if it doesn't show anything, what the chances of a false negative might be - might there still be an undetected genetic predisposition even if the study did not show it. Is that something you might be able to find out @Andy - doesn't feel right for me to be bugging Chris Ponting about it at this time.

 

[Sasha]

Do you have to get past the paywall to see this?

You can see it in Andy's post that I linked to. Whipple's piece is the last one on that page.

 

[Andy]

Firstly, I am not at all qualified medically or scientifically, so this is purely my own uneducated thoughts.

I would guess that if there really is a genetic predisposition to having ME/CFS, then there might be a good chance this study might identify it. If there isn't then of course there would be nothing to find. What I don't know is if it doesn't show anything, what the chances of a false negative might be - might there still be an undetected genetic predisposition even if the study did not show it. Is that something you might be able to find out @Andy - doesn't feel right for me to be bugging Chris Ponting about it at this time.

Obviously Chris, or @Simon M , would be the best person to answer this. My understanding is that with 20k participants the chance of a false negative is small enough to not be a concern.

 

[Barry]

I would guess that if there really is a genetic predisposition to having ME/CFS, then there might be a good chance this study might identify it. If there isn't then of course there would be nothing to find. What I don't know is if it doesn't show anything, what the chances of a false negative might be - might there still be an undetected genetic predisposition even if the study did not show it.

Obviously Chris, or @Simon M , would be the best person to answer this. My understanding is that with 20k participants the chance of a false negative is small enough to not be a concern.

Yes of course! @Simon M, do you have some insights on this?

 

[mango]

Merged thread

Article in The Times: Chronic Fatigue Syndrome: ‘It felt like I’d been in a car crash’

Ali McNamara is a well-known author of romcom/chick lit books, for example the From Notting Hill with Love... Actually series.

https://www.thetimes.co.uk/article/...it-felt-like-id-been-in-a-car-crash-9nrk56fcb

Asked what would change his life, a 14-year-old boy with ME said that what would help most was “being believed”.

Time and again in more than 4,000 written testimonies from a survey of ME sufferers, the desire to be believed is articulated.

Patients tell of extreme pain in muscles and joints, limbs that won’t respond to command, struggles to perform basic tasks, exhaustion after activity, “brain fog”, sleep that brings no rest, hypersensitivity to light and noise and, in the most severe cases, being bedridden.

Far too often, they say, health professionals tell them that these symptoms are caused by mental health problems or anxiety. [...]

The article is behind a paywall, but screenshots are available on her Facebook page:

 

[MeSci]

Sure. As I explained up-thread, the original sign-up and the sign-up that is available on the website (www.decodeme.org.uk for those who missed it..) now was to get onto the mailing list for updates and notification when recruitment is open. Once recruitment is open (March 2021), anybody who is willing to take part will need to sign-up to the study, even if you have signed up to our mailing list previously.

We will obviously promote any update, and the opening of recruitment, widely, so if you are going to regain access to your email address at some point then I'd suggest not doing anything, if you aren't, then I'd suggest signing up with your new email address, but, either way, it will not affect your ability to apply to participate in the study.

Hope that clarifies it.

I've already signed up with my new email, and don't know if I will regain access to my old address. But hopefully I'll read of any updates on this site!

 

[Sunshine3]

How long is this study going to take? Approximately? I haven't read all info as reading a problem for me.

 

[wigglethemouse]

I would guess that if there really is a genetic predisposition to having ME/CFS, then there might be a good chance this study might identify it. If there isn't then of course there would be nothing to find. What I don't know is if it doesn't show anything, what the chances of a false negative might be - might there still be an undetected genetic predisposition even if the study did not show it. Is that something you might be able to find out @Andy - doesn't feel right for me to be bugging Chris Ponting about it at this time.

The 20,000 ME/CFS participants will likely include people with known genetic diseases with rare variants. As part of quality control GWAS studies filter out small populations of patients with rare variants (e.g. population frequency < 0.1%, or 20 in 20,000). These type of rare variants that cause disease are only likely to be found in family studies where multiple affected family members have the same variant.

 

[daftasabrush]

That article was great. Superb interview with Muirhead. Much better report than the Guardian, who as usual can't resist a knife to our back. That picture is so insulting.

When I read the Guardian piece, right next to it was the BPS grievances report about the "perils" of online activism, how ironic. The "perils" are a large genetic study, impressive for an "anti-science" community. This study is the result of years of relentless activism. Though it's true that this is the most perilous of outcomes for our BPS overlords. Seeing other ME coverage below the article shows how much of a mess of things the Guardian has made.

Congrats to everyone who made it happen! This is really big news.

I had not thought of the public reaction and I think it would be really important to record the inevitable rantings on the "Bad ME quotes" thread. There will be a lot of angry people spewing vitriol at us, including the people who have been screaming "ACADEMIC FREEDOM" for years but somehow don't share the same sentiment when it comes to real research.

I noticed that too - awful

 

[daftasabrush]

It cannot show nothing. Even if there are no gene associations at all that would be a crucial piece of information. It would also be a very important thing to explain, since there is evidence for a genetic component from epidemiological studies. The great thing about a study like this is that it will get the true answer whatever it is. And you get to the ultimate answer in this game by excluding possibilities at least as much as by including them.

The likelihood is that it will pick up some links though and that could take use directly to a relevant pathway.

Klimas's team have published preliminary results showing 3 different areas, so yes - lookup the ME/CFS Gene Study

 

[Sasha]

Klimas's team have published preliminary results showing 3 different areas, so yes - lookup the ME/CFS Gene Study

There's an MEpedia page on it here. It only mentions the MTHFR mutation, though.

 

[Andy]

How long is this study going to take? Approximately? I haven't read all info as reading a problem for me.

Four years, shorter if recruitment goes well.

 

[daftasabrush]

The Open Medicine Foundation/Robert Phair's metabolic trap theory was based on the severely ill big data study and found IDO2 and possibly IDO1 defects which affected the tryptophan / kynurenine pathway (metabolism).

Klimas's ME/CFS Gene Study at Nova Southeastern is still recruiting if you have your own 23AndMe or Ancestry DNA data that you are willing to send electronically. Preliminary study was Nov? Dec? 2019 showing 3 areas, one was the HPG axis (not HPA) which may be linked to female predominance and something or other about the endocrine / neuroendocrine system (eg can't regulate body temperature). The other two areas they found were immune system and metabolism I think. Klimas' study has 20ish optional questionnaires and aims to collect data for 10 years with many publications.

Sorry crashing too bad to link to studies or think right.

But YES gene differences already found.
Previous studies have been tiny.

Study will be GWAS which is way more data than 23AndMe (I believe).

I read Canadian Consensus Criteria OR SEID criteria only. Hopefully this means comparing data for both.

Anyone know why CCC is preferred over ICC by pretty much all researchers?
Can't recall the key differences.


(Apologies for inevitable mistakes and not linking. I usually only visit here on better days).

 

[Jonathan Edwards]

What I don't know is if it doesn't show anything, what the chances of a false negative might be - might there still be an undetected genetic predisposition even if the study did not show it.

My understanding is that the chances of a false negative for genuinely significant predispositions in the normally understood sense is remote. If anything, my experience of genetic predispositions is that they show up with smaller numbers.

But there is something lurking the background that is not just a problem for ME/CFS. In other areas epidemiology such as twin studies has shown a clear level of genetic predisposition but specific genes that account for the predisposition have been hard to locate. What this may mean is that combinations of genes confer risk but individual genes do not. An analogy would be that heart cards do not confer any special merit in Poker but if you have five of them you have a flush.

At the moment it looks to me that there may be a mismatch between genetic risk shown by epidemiology and by gene association in ME and if there is then it becomes a very interesting problem that needs sorting out.

In other words finding no gene linkages does not necessarily mean that genes are not involved. What you might call a misleading negative perhaps.

 

[daftasabrush]

There's an MEpedia page on it here. It only mentions the MTHFR mutation, though.

Thank you Sasha!! Klimas ME/CFS Gene Study prelim results, spoonie version

(Link to the thread on this study:
Genetic Predisposition for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Pilot Study 2019 Perez Nathanson Klimas et al)

 

[Barry]

My understanding is that the chances of a false negative for genuinely significant predispositions in the normally understood sense is remote. If anything, my experience of genetic predispositions is that they show up with smaller numbers.

But there is something lurking the background that is not just a problem for ME/CFS. In other areas epidemiology such as twin studies has shown a clear level of genetic predisposition but specific genes that account for the predisposition have been hard to locate. What this may mean is that combinations of genes confer risk but individual genes do not. An analogy would be that heart cards do not confer any special merit in Poker but if you have five of them you have a flush.

At the moment it looks to me that there may be a mismatch between genetic risk shown by epidemiology and by gene association in ME and if there is then it becomes a very interesting problem that needs sorting out.

In other words finding no gene linkages does not necessarily mean that genes are not involved. What you might call a misleading negative perhaps.

Ooh ... I need to think about that one to get my head round it.

 

[Hoopoe]

At the moment it looks to me that there may be a mismatch between genetic risk shown by epidemiology and by gene association in ME and if there is then it becomes a very interesting problem that needs sorting out.

Can you better explain what you mean?

By genetic risk shown by epidemiology, do you mean something like twin studies showing that there is an inherited component?

The situation with studies attempting to find the associated genes appears to be one where every group gets different results.

 

[Milo]

Congratulations to everyone who worked on this grant application and that made it successful. This is great news for all of us around the world.

 

[lunarainbows]

The Open Medicine Foundation/Robert Phair's metabolic trap theory was based on the severely ill big data study and found IDO2 and possibly IDO1 defects which affected the tryptophan / kynurenine pathway (metabolism).

Klimas's ME/CFS Gene Study at Nova Southeastern is still recruiting if you have your own 23AndMe or Ancestry DNA data that you are willing to send electronically. Preliminary study was Nov? Dec? 2019 showing 3 areas, one was the HPG axis (not HPA) which may be linked to female predominance and something or other about the endocrine / neuroendocrine system (eg can't regulate body temperature). The other two areas they found were immune system and metabolism I think. Klimas' study has 20ish optional questionnaires and aims to collect data for 10 years with many publications.

Sorry crashing too bad to link to studies or think right.

But YES gene differences already found.
Previous studies have been tiny.

Study will be GWAS which is way more data than 23AndMe (I believe).

I read Canadian Consensus Criteria OR SEID criteria only. Hopefully this means comparing data for both.

Anyone know why CCC is preferred over ICC by pretty much all researchers?
Can't recall the key differences.


(Apologies for inevitable mistakes and not linking. I usually only visit here on better days).

Im pretty sure I found links to articles in the Guardian on another thread re 23andME that showed that 23andME has a 40% false positive rate for at least some of the mutations. How can Klimas draw any conclusions from that type of inaccurate data?

edit:
Eg:https://www.theguardian.com/science...ll-for-crackdown-on-home-genetic-testing-kits
https://www.nytimes.com/2018/07/02/health/gene-testing-disease-nyt.html
https://www.nytimes.com/2018/07/02/health/gene-testing-disease-nyt.html

And: https://www.nature.com/articles/gim201838

 

[Jonathan Edwards]

By genetic risk shown by epidemiology, do you mean something like twin studies showing that there is an inherited component?

The situation with studies attempting to find the associated genes appears to be one where every group gets different results.

Yes, if monozygotic twins both have an illness more often than dizygotic the usual interpretation is that this is good evidence for a genetic component. So a screening for risk genes should find some. But it seems that you don't necessarily find risk genes that confer the expected level of risk.

In most conditions where several risk genes are known the genes seem to have individual risk that adds or multiplies to the risk from other genes. That applies to HLA-DR4 and PTPN22 genes in rheumatoid. But it is conceivable that there are genes that confer no risk on their own but do confer risk in combinations.

A hypothetical example might be HLA-B genes and NK KIR receptor genes. You might have increased risk if you have HLA-B51 and KIR variant 6 (this is invented, I forget the nomenclature). You might also have risk if you have HLA-B27 and KIR variant 4. But across the board none of the genes increases risk alone. HLA-B proteins bind to KIR proteins and both come in variants that bind more or less effectively to variants of the other. Risk might be a matter of having a 'tight match' rather than having any particular version of either.