UK Genome Wide Association Study (GWAS) project - draft website goes live, feedback sought on recruitment plan, and updates

[Jonathan Edwards]

Wouldn't a more mixed cohort be better - provided controls are well matched - to avoid getting a signal linked to being English?

You don't get a signal linked to being English if you control within an English population. Anything linked to being English cancels out. The study only looks at differences. You might only discover the cause of ME/CFS in England but nobody is going to complain if something is actually found - it would almost certainly point the way to finding the cause in other countries, if, say, a different microbe or eating habit was more important there.

 

[ME/CFS Skeptic]

If I remember rightly the US study that looked at ME/CFS diagnosis by physician indicated that physicians over diagnose ME/CFS by about five fold. Patients' responses to questionnaires were more reliable and produced a smaller cohort.

Not sure what study you're referring to here.

 

[Andy]

As I understand it, we won't be looking to recruit controls, as we plan to use the genetic data on 500k people that the UK Biobank (not to be confused with the UK ME/CFS Biobank) holds.

 

[Jonathan Edwards]

As I understand it, we won't be looking to recruit controls, as we plan to use the genetic data on 500k people that the UK Biobank (not to be confused with the UK ME/CFS Biobank) holds.

Yes, the controls are already fixed and that is why it is so crucial to recruit from a matched population.

 

[Jonathan Edwards]

Not sure what study you're referring to here.

I forget but I think Lenny Jason was involved. There was a US study that showed that something like 80% of people who had been diagnosed with ME or CFS by a doctor did not fit criteria. I suspect that in the UK ME Biobank study the discrepancy was rathe less.

 

[ME/CFS Skeptic]

I forget but I think Lenny Jason was involved. There was a US study that showed that something like 80% of people who had been diagnosed with ME or CFS by a doctor did not fit criteria.

That would surprise me, to be honest.

Anyone else knows which study this could have been?

 

[Jonathan Edwards]

That would surprise me, to be honest.

Anyone else knows which study this could have been?

It slightly surprised me at the time but I have a pretty clear recollection of it. Somebody will remember. I think it was the prevalence study done by questionnaire that Jason did a good while ago.

 

[Kitty]

Anyone else knows which study this could have been?

I'm not familiar with it, but there's a list of his studies here in case anyone recognises the title:

https://me-pedia.org/wiki/Research_studies_of_Leonard_Jason

 

[Hoopoe]

@Chris PontingThis may be of some interest:

Dominic Cummings, adviser to the UK prime minister Boris Johnson, met academics at 10 Downing Street to discuss setting up a UK version of the US Advanced Research Projects Agency (ARPA) that would tackle “really big societal challenges”.

Cummings has been keen on the idea for some time. Writing on his blog in 2017, he said that as the UK prepares to exit the European Union it “should think hard” about the example of ARPA and “how a small group of people can make a huge breakthrough with little money but the right structure”.

Yes. How about solving the problem of "medically unexplained symptoms" or ME/CFS and similar conditions in a serious way? We patients want our old productive lives back. We need good treatments for that and to get them we need to understand the underlying biology.

https://www.newscientist.com/articl...nic-cummings-plan-for-new-uk-research-agency/

 

[lunarainbows]

@Chris PontingThis may be of some interest:



Yes. How about solving the problem of "medically unexplained symptoms" or ME/CFS and similar conditions in a serious way? We patients want our old productive lives back. We need good treatments for that, and we need to understand the underlying biology which we currently do not because we don't have the tools and knowledge and funding. A committed research agency with long term funding could greatly help with that.

https://www.newscientist.com/articl...nic-cummings-plan-for-new-uk-research-agency/

yes except in the same article - the ARPA which it would be modelled on seems to have morphed into defence research. That’s not helpful for ME research.

“ARPA was founded in 1958 and helped create ARPANET, an early version of the internet. It was later renamed the Defense Advanced Research Projects Agency (DARPA) and now focuses on developing new technology for the US military.“

And

“However, researchers questioned the need for a new research agency and said its goals could be achieved through existing institutions, with more money.

“The ambitions are all sensible and laudable,” says James Wilsdon at the University of Sheffield. “The thing I find bizarre is the focus on creating a new institution. There is nothing in there [on the UK ARPA proposals] that cannot be achieved in the existing situation with UKRI.”

 

[Hoopoe]

Molecular biology is specifically mentioned as possible area of research.

 

[Ravn]

As I understand it, we won't be looking to recruit controls, as we plan to use the genetic data on 500k people that the UK Biobank (not to be confused with the UK ME/CFS Biobank) holds.

Yes, the controls are already fixed and that is why it is so crucial to recruit from a matched population.

So the best-possible second cohort would be from a country that also has a large general (not disease-specific) biobank to source controls from?

To be clear, I agree that the preferred options by far would be having a tight English or UK cohort. I'm just trying to get my head around the best possible alternatives should international recruitment become necessary.

You might only discover the cause of ME/CFS in England

That was what I meant with "signal linked to being English". But also this: given that it's likely there are different triggers that all lead to ME, is it conceivable that there could also be more than one genetic ME predisposition? Which could be more or less common in different populations? And/or interact with an environmental factor more or less common in different locations to kick off ME?
Better stop here, I've thoroughly confused myself

 

[Adrian]

I forget but I think Lenny Jason was involved. There was a US study that showed that something like 80% of people who had been diagnosed with ME or CFS by a doctor did not fit criteria. I suspect that in the UK ME Biobank study the discrepancy was rathe less.

I think Jason has done a number of studies looking at different criteria and comparing them in terms of the numbers of patients covered as compared to cohorts from doctors with ME experience. I think he has also looked at the overall effectiveness of his depauls questionnaire which may be where that figure comes from.

There were studies from the UK (I think Julia Newton and White (2 separate studies)) which showed that 50% of patients referred to specialist centers were given an alternative diagnosis - which could be quite remarkable these days since specialist centers don't seem to have doctors anymore.

 

[Jonathan Edwards]

is it conceivable that there could also be more than one genetic ME predisposition?

I think it would be pretty unlikely. If a signal came up in one population another population with a Biobank would certainly be a good place to get confirmation.

 

[Adrian]

I'm a big fan of the idea of patients reaching out via their social networks but I think this is an optimistic calculation. Outside of this forum, I don't know a single other ME patient and am not aware that I have any friends or relatives who know one. Even if I blast out an email to everyone I know (which I fully intend to once we've got a site properly up and running), I don't expect to reach many PwME. And those that I do reach might be less enthused about the study than me and so less likely to pass the message on. Plus, some of us will inevitably reach some of the same people.

I hope that 20k is doable but if it is, I think it's going to take everything we've got, and will need all hands on deck, and will need some serious PR work being done by the researchers.

I wonder if there is also an issue if there are too many people in the same families (i.e. if a high proportion of those included also have a member of the family with ME who is included how will that squew any genetic results).

I think 20000 will be difficult but should be possible.

 

[Adrian]

Assume we can persuade 14,000 people with ME (40% of the UK patient community with a diagnosis) to register. Then assume that 45% of them completed the questionnaire, passed the online screen and returned a saliva sample (better than comparable studies), that would generate 6500 participants.

I think there has been mention of access to medical records which is another potential way to find patients. I don't know how medical records are organized (whether they are structured data or just text fields) but these days even if there are just free text there are some very good toolkits to do natural language processing that could be used to pick out potential candidates.

 

[Adrian]

And then there is what one might perhaps call the people with 'closet ME'. That term may be a bit too strong but I have reason to think from what people say on the forums and from social contacts that quite a lot of people with ME prefer to keep the fact to themselves and maybe not even admit to themselves that they have an illness seen largely as defined and 'owned' by clinical psychology.

I wonder if there will be a problem that there will be a number of people who don't have an ME/CFS diagnosis but all the symptoms (perhaps in a mild form) and hence don't identify with the disease. There will be a number who are told they have depression who don't have an ME diagnosis etc

So when we say 250000 people in the UK I wonder if that number should be halfed in terms of people with an actual diagnosis.

 

[Jonathan Edwards]

So when we say 250000 people in the UK I wonder if that number should be halfed in terms of people with an actual diagnosis.

0.2% of 60million makes 120,000 to me. That is based on diagnosed cases. No doubt there will be more undiagnosed cases but goodness knows how many.

 

[Andy]

Website update.

No major content changes but lots of editing has happened following feedback from the community. Feel free to continue leaving feedback here or PM me.

https://mebiomed.org.uk/

 

[MerryB]

I think there has been mention of access to medical records which is another potential way to find patients. I don't know how medical records are organized (whether they are structured data or just text fields) but these days even if there are just free text there are some very good toolkits to do natural language processing that could be used to pick out potential candidates.

I may be wrong, but I don't think that method would be possible due to GDPR rules. Patients have to give permission for their medical records to be shared with researchers, unless it's anonymised data.

As far as I understand, medical records contain codes information which can easily be anonymised and is used e.g. to inform healthcare policy, free-text notes which I think would require the patient's permission to share because they are more detailed, and scanned/attached documents, which may or may not be suitable for text-searching software.

I think the only way to legally use text analysis would be if the patient was first identified and gave permission to share their record. I don't think this method could legally be used to identify potential participants, especially undiagnosed participants.

I suspect that the only legal way under GDPR would be to ask GPs and other NHS services to recommend the study to their diagnosed patients, and to ask them to put up posters etc.

I am not even sure it is legal any more for GP surgeries to contact patients by letter or phone to invite them to participate in research, unless the patient has ticked a box when registering with the surgery to say they are happy to be contacted about research.

I suspect that if the patient hasn't ticked such a box, the only legal way would be for healthcare professionals to mention the study when they see patients in person, and to have posters up around their clinics, and to put adverts for the study in their websites.

Somebody please correct me if I am wrong, but my understanding is that patient contact information and medical records can only be used for research purposes of the patient has given prior consent (including consent to be contacted about research studies they might qualify for), unless it's just the anonymised codes data being used for e.g. NHS service evaluation, strategy, and epidemiological surveillance.

Again, correct me if I am wrong!