Trial By Error: The UK’s Proposed Genetics Study

In the UK, leading researchers are preparing to submit an application for a large genetic study to two major funding agencies. The project is being led by Professor Chris Ponting of the University of Edinburgh, who is also vice chair of the CFS/ME Research Collaborative, and the UK ME/CFS Biobank at the London School of Hygiene & Tropical Medicine. I have a lot of respect for both Professor Ponting and Dr Luis Nacul, a clinical associate professor of epidemiology and public health at LSHTM and the co-principal investigator of CureME, the research unit at the university that hosts the biobank.

The funding application deadline is January 23rd. The ME/CFS Biomedical Partnership, a group developed to support the study, has posted an FAQ here and a form to demonstrate support for the study here. On his invaluable blog, ME/CFS Research Review, Simon McGrath recently wrote about the new project.

Here’s what he had to say in his post:

Researchers and patients are about to submit an application to the UK’s two big medical research funders for a 20,000-patient genetic study. The team want people with ME to sign up to show funders that the community backs the study and that large numbers of people are ready to join it.

Your action today could help the world’s largest ME/CFS genetics study win funding – and could make a huge difference for patients, helping to identify biological causes of the illness and unlocking far more UK funding for biomedical research.

On 23rd January, the ME/CFS Biomedical Partnership made up of researchers, people with ME/CFS and carers, will make a grant application to the Medical Research Council and the National Institute for Health Research.  The Partnership needs £3.5 million for a very large genetic study into ME/CFS known as a genome-wide association study (GWAS).

The project will be led by Professor Chris Ponting at the University of Edinburgh in partnership with the UK ME/CFS Biobank at the London School of Hygiene & Tropical Medicine.

A GWAS aims to uncover some of the biological roots of disease. By scanning the whole of human biology and probing small DNA differences among people, a GWAS can help to pinpoint the genetic causes of disease and then can help to guide drug development. This method has helped to identify genes – and the molecular and cellular pathways associated with them – that play a role in diseases such as rheumatoid arthritis and Type II diabetes. (See my blog about the science of GWAS).

Drug development is now under way in numerous diseases because of GWAS. This, and the identification of biomarkers, could happen for ME/CFS too.

Because researchers are looking at small differences, they need to look at DNA data from a lot of people. The ME/CFS study will recruit around 20,000 patients whose DNA will be compared with that of similar numbers of people who do not have the disease. The DNA will be extracted from saliva samples, and the study uses a “spit and post” design, so even people who are bedbound or housebound can take part.

Sign up!

3 more reasons to back the project

1. Another big reason to support the study is that it includes creating a research cohort of 20,000 people – each clinically diagnosed with ME/CFS and who meet either the Canadian Consensus or Institute of Medicine (now called the National Academy of Medicine) criteria, both of which are widely used in biomedical research. The Partnership will set up a system to give other researchers easy access to DNA data, questionnaire answers and other information on this large number of people. This huge resource will help other researchers create robust studies more easily. The data will be made anonymous and held safely and securely.

2. All participants will be asked if they would be willing to be contacted in future about taking part in further studies. The hope is that the overwhelming majority of patients will say yes. Being able to easily recruit many patients will help researchers and should lead to better and faster research – and so more progress.

3. Patients are at the heart of this study. There is a Public Patient Involvement steering group with representation from patients and all the main charities. Two representatives, Sonya Chowdhury, CEO of Action for ME and a carer for someone with ME/CFS, and Andy Devereux-Cooke, a patient, are co-investigators on the study and sit on the management committee alongside two researchers.

Patients and charities have already started reaching out to other patients to sign up for the study, because the higher the number of sign-ups, the more the funding bodies will understand the need for the study and be reassured that patients will support it. Over 4,000 patients have already signed up in just two weeks over the holiday season. And we need more – could we make 10,000?

Sign up!

Speed is, of course, of the essence for patients. We’ve waited so long for good biomedical research, and for treatment. And the more patients who’ve said that they want to take part and want to be contacted if the work is funded, the faster the work can go. Signing up now should speed up the work later.

As Professor Chris Ponting says, “Patients with ME/CFS deserve the best that biomedical science has to offer, and it’s long overdue. But to get enough patients, fast enough, we’ll need a community-wide effort. Signing up early, and in large numbers, is the best way for patients to help us help them right now.”

{ 15 comments… add one }
  • Sally Richardson 13 January 2020, 4:44 pm

    It’s about time we had a large genetic study so funding please – and I’d happily take part

  • Lady Shambles 14 January 2020, 6:18 am

    I have 2 major concerns.

    i) AFME is involved… massive red flag for me.

    ii) the cohort is self selected and we already know that the numbers of people with a misdiagnosis of ME (or CFS ..whatever that is) is high.. between 40% and I think as much as 60%. Centres that use multiple hands-on/in person diagnostic tools (which of course involves searching for other known alternative diagnoses) including using the tightest criteria, ICC, find that many patients do not make the ‘cut’. Trying to co-opt 20,000 people with ME at arm’s length and then assessing them using questionnaires isn’t likely to provide a very clean cohort. Self selection plus subjective questionnaires… that ain’t a good start is it? Actually, imo, it’s the sort of ‘sloppy science’ for which we’ve been criticising the BPS school for many a day now.

    I agree that “Patients with ME/CFS deserve the best that biomedical science has to offer, and it’s long overdue” but I’m not convinced that many scientists would regard this sort of cohort as representing the ‘best’ that can be offered.

    Thus I’m conflicted. Part of me feels this is an utterly pointless waste of money which could be better spent, and part of me thinks it would wise to ensure my dna is included if only to skew a dirty database toward some meaningful data… BUT even I can’t be 100% sure of my diagnosis despite it coming from 4 different sources (none of which I really credit with understanding what ME really is) and having to rely on a very fragmented 50 year history of the disease where I’ve tried to rule out other diagnoses (mainly paid for privately) before coming to the conclusion that fitting both ICC and Ramsay criteria lends some weight to the diagnosis I’m lumbered with.
    I wish I could be part of VanElzakker’s cohort simply to access the comprehensive testing that is part of the selection process so that I could be more sure of the diagnosis I have. VanElzakker’s is a team which takes the ‘scientific method’ seriously and properly screens to ensure (as well as medical science can presently manage) that the diagnosis of ME is the correct one.. I’m not sure that what’s on offer here can do that. I’d be interested to hear how the team think they can overcome the sullying that possibly one in every two people told they have ME (or CFS??) don’t have it?

    Where tight cohorts have been used lately (and by that I mean ICC face to face screening etc) we’re seeing some really interesting results emerge. I’m guessing the tight cohort is the reason behind that… it makes sense. It’s a shame the good guys amongst the proposal above (and I do believe there are some ‘good guys’ in the mix) want to be involved with this clunky proposal. I can quite understand that mass dna data collection of people who really unarguably have ME might throw up some interesting data, but can a muddy cohort like this do that? I just can’t see it.

  • CT 14 January 2020, 6:27 am

    I hope that this study will be wholly focussed on biomedical research as the website suggests and won’t, at any time, lapse into anything related to the BPS approach, be that via researchers involved, the type of information gathered or the use of information gathered. Trust is easily lost but so hard to regain. ME sufferers must not be misled again.

  • jimells 14 January 2020, 9:44 am

    “This method has helped to identify genes … that play a role in diseases such as rheumatoid arthritis and Type II diabetes”

    If these are the best two examples of actual GWAS results, then mark me down as unimpressed and extremely skeptical of this approach. As far as I can understand, GWAS played no role in Professor Edwards’ development of an effective treatment for RA, and there is no effective treatment for Type II diabetes.

    I started writing computer software for a living in 1974. I was forced to stop in 2007 due to this horrid disease. One thing I learned early on is that there is no magic in computers. And this sounds an awful lot like magic.

  • Wendy Boutilier 14 January 2020, 10:37 am

    With AFME involved we already know the results will reflect cherry picked science. It’s time for everyone to recognize that poor science and poor participation selection will only extend the decades we have already suffered.

  • Janice Johnson 15 January 2020, 12:48 pm

    I’m sorry. I’m not impressed by this. We’ve been let down (shafted) too many times before

  • Guido Den Broeder 15 January 2020, 1:21 pm

    This will be worse than PACE. What happened to independent journalism?

  • Colleen Steckel 15 January 2020, 2:33 pm

    “The ME/CFS study will recruit around 20,000 patients whose DNA will be compared with that of similar numbers of people who do not have the disease.”

    Which disease? In order for good science we must reduce the variables. We know that ME and CFS are listed as two different conditions in the IOM report which went on to combine those two conditions under one umbrella (removing the most devastating symptoms that are unique to ME).

    Patients across the globe KNOW that doctors are ill equipped to diagnose. Even the best of our doctors have been known to miss other conditions or diseases for far too many patients.

    We need to get our ducks in a row before wasting money on research that can’t be realistically reliable. It is time we made sure anyone in an “ME” study was thoroughly screened for other diseases. We need diagnosis using the ICC followed up by ruling out other diseases for a common sense approach to getting the science right.

    I am not aware that normal data bank systems have any system in place to remove data that no longer applies to the study. So it’s imperative that we get the right dataset to start with.

  • Trish Davis 15 January 2020, 4:56 pm

    I am as concerned as everyone else that we get good quality biomedical research for ME/CFS. The scientists involved in this GWAS study understand the importance of accurate diagnosis. Diagnosis will, as I understand it, be based on both IOM and CCC criteria, using the questionnaires used by the UK ME/CFS biobank with PEM as a mandatory symptom. It is a genetic study, not a psychosocial study, and will be carried out by experts in these sorts of GWAS studies.

    I do understand some people’s anxiety about Action for ME’s involvement, given their track record, but I think those concerns are misplaced in this instance. I was against the previous CMRC plans for the genetic study called MEGA which would have been led by Esther Crawley because I was afraid she would misuse questionnaire data for psychosocial studies and use too wide a definition of ME.

    I don’t have those worries with this study. I trust the scientists involved and am satisfied they will do the best they can to get a cohort of patients who have ME/CFS. I am very pleased this study is planned and fully support it.

  • Alicia Butcher Ehrhardt 16 January 2020, 2:24 am

    If they only want people from the UK (likely?) or will be recruiting world- or Europe-wide – it should say so.

  • @MECFSNews 16 January 2020, 6:21 am

    I think this is a very worthwhile project. We have never had such a study before and it could help explain what causes the illness and help us identify subgroups.

    To respond to concerns that this will leave out patients with ME as defined by the ICC: it will not, or at least there is no good reason in my eyes to think that it will. I understand that with 20000 participants the statistical power should be more than enough to overcome misdignoses and existence of subgroups in the data.

  • Jonathan Edwards 16 January 2020, 6:27 am

    Just to mention to Jimells, genetic information on MHC Class II that came from what was equivalent of GWAS in the 1970s was absolutely essential to my work on rheumatoid arthritis. Further GWAS work in the 1990s also helped. RA is an excellent example. The genetic work laid the foundation for any meaningful theory of aetiology.

  • Lady Shambles 16 January 2020, 6:57 am

    I see that supportive comments have been made subsequent to an appeal for them on S4ME forum. Everyone is entitled to their opinion on this, but I am still unable to fathom how questionnaires can properly ‘un-muddy’ a dirty cohort. At the very least it would seem eminently possible to include the quick-response questionnaire ‘Do I fit the International Consensus Criteria?’ (here: and use pretty basic algorithms to sieve out data specifically associated with that cohort. For those who support this enterprise I think having that option would at least partly satisfy the ‘small clique..of extremists’ who can see the folly of this venture as presently described.

  • jimells 16 January 2020, 9:15 am

    Professor Edwards, thank you for the explanation. I’m not qualified to have an opinion on whether or not this research will be useful. Many years of illness and abuse by the medical industry has taught me to have a very cynical view of the medical research field, so my initial reaction to pretty much all research is, “Is it research or just more marketing?”

  • CT 16 January 2020, 9:51 am

    Lady Shambles’ suggestion above to include the quick-response questionnaire ‘Do I fit the International Consensus Criteria?’ WITHIN the study that will be based on the CCC/IoM seems a very sensible proposal and one that I suspect could be implemented with minimal additional burden on patients and researchers. Why wouldn’t you do this? Why would you give up the opportunity of seeing how 20,000 patients compare using the ICC criteria too (within the study) when it appears to be such an easy thing to enact and when other researchers are using the ICC criteria in their work? This sounds like an excellent compromise solution that might satisfy all camps and make more people want to participate.

    I do understand why people are reluctant to take part in this study. When funders are involved, there will always be a trust issue as to whether pressure is being brought to bear to use particular criteria or look at particular aspects. But there is also the time issue. Some patients are desperate NOW, and finding answers quickly is literally a matter of life or death to them, so if a study uses criteria that are too broad to ‘catch’ key markers then a lot of time will have been wasted that they can’t afford. Decades have already been wasted. This study needs to be spot on and the researchers must convince patients that it is. So I would appeal to them to seriously consider this proposal and sell it to their funders.

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