DecodeME - UK ME/CFS DNA study underway

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.

 

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

 

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?

 

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

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

 

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!

 

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

 

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.

 

I noticed that too - awful

 

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.

 

Four years, shorter if recruitment goes well.

 

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).

 

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.

 

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)

 

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

 

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.

 

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.

 

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

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

 

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.