Initial DNA results - August 2025 webinar

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SONYA

Welcome, everybody, to the Decode ME initial results webinar. A special welcome to those of you on Facebook. We know we only had 3,000 spots on the webinar, so we are live streaming to Facebook as well, so welcome to everybody watching and also welcome to those of you that are watching afterwards.

I can't tell you how excited we are to have this webinar today. Many of us on the team have shed several tears, and we've been totally blown away by the feedback and the comments and the impact that the results are already having for you. As I said, it’s a bit emotional. This has been an incredible journey, and we're delighted today to be able to share the initial results with you.

So, I'm just going to run through the things that we will cover on the agenda.

We're going to start with how we got here. There are many people that will have heard this before and know all about this study, but we know that we've got new people listening in to the webinar for the first time. We'll then hand over to Chris, who will talk about our results, and what this means. Andy's going to say a little bit about the response to the results, and then we'll come back to me to talk a little bit about what happens next. Then there's an opportunity for questions and answers. As always, we are expecting to be inundated with questions. We will not get to all of them, but we will be updating our frequently asked questions afterwards so that we can cover as much as we can, and you can find those at www.decodeme.org.uk and we will get to as many as we can through the session. Please do not ask any questions about yourself or give any personal information, people can see the questions you're asking. We also can't answer every question, and certainly not any questions that are related to your medical history so please save your valuable energy, because we just won't be able to pick up those questions.

This is the world's largest ME study, not just the genetic study, but the world's largest ME study, and many of you listening will have participated. This study came from people with ME and carers and others, and as a group, we worked together as charities and researchers and people with lived experience to call for a genetic study. We went through lots of different iterations of what the research team would look like, what we were going to do, how we were going to do it, who we were going to work with, and so on. But at the heart of it has been people with lived experience. We believe our study is not just stronger as a result of that, in terms of the recruitment and the trust that you've given to us, but actually, it is scientifically better as a result, and Chris will say more about that, I'm sure. It has taken years - we have been working on this study for four-plus years in terms of delivery, but there were many, many years that went before that, and there are many people, like Professor Sir Stephen Holgate and others, that have been involved from the beginning.

So, I want to thank each and every one of you that has been involved, and that includes people who gave us lots of ideas around recruitment as we were submitting our application.

Our objectives were threefold. The first one was to identify genetic differences in people with ME, and to start to explain the biological mechanisms behind the disease. There have been other genetic studies. Ours is bigger, it is more statistically powered, and therefore we can have greater confidence, and Chris will also talk about some of the validation that's already started too. Secondly, we wanted to build a clearly defined cohort of people with ME for future research, and so the detailed questionnaire that our participants completed was really valuable, and it helped us ensure the post-exertional malaise was absolutely critical in identifying those people that met the very strict research criteria that we had, and so thank you to everybody who gave up their valuable energy to do that. You can see the report of our publication of the results from the first 17,000 people that completed that questionnaire, and I'm sure at some point one of the team will pop that in the chat for you. Thirdly, we wanted to disseminate the data to academics and industry, and we will come back to that in a bit.

So, as I said, this is a co-production at every single level, and Andy who is one of our management team has been with us right from the very beginning, but there are many others that are sitting behind the scenes that have been involved, and you can read more about that on the website. And we've recruited over 26,000 people to participate, who completed the questionnaire and then a number of people went on to provide genetic data for us, too. So I'm now going to hand over Chris to say a bit more about the results.

CHRIS

Thank you, Sonya. So, what DecodeME has discovered is that genetic variation contributes to everyone's risk of developing ME/CFS. DecodeME has discovered 8 places in our genomes where people with ME have genetic differences more often than the general population. What we have on the right-hand side here is what is called a Manhattan plot. On the bottom are indicated the human chromosomes 1 to 22, we haven't yet analyzed the X chromosome, and that's to come in the future.

On the y-axis, this represents the degree of significance of association, and any signal that pops its head above the horizontal dashed line, represents a significant genetic signal, meaning that there are genetic variants within that signal

that are more frequent among people with ME than the general population. What we've done here is to label each of these signals by one of several genes that lie in this signal, so these are not unique.

DecodeME has provided, therefore, the first robust evidence for genetic contributions to ME/CFS risk. It isn't that there is a single signal that has all of the genetics within it. There are many signals, there are 8 that we have listed here, but there will be more, if and when larger studies are done in the same way.

So, because it doesn't affect one gene, this means that it is not deterministic. It does not determine whether someone or not has ME. Now, DNA doesn't change from birth onwards, and because we have taken account of various factors that could otherwise confound the study, what we then can say is that the discovery that we are showing here, reflects causes and not downstream effects of ME/CFS.  

So, what can we say about these 8 genetic signals? Well, in general, we can say that they point to the immune system and the nervous system involvement in ME cause. For example, two signals that likely relate to the body's response to infection, BTN2A2 and OLFM4, and OLFM4 in particular, is more significant among those who reported an infection before their first onset of ME symptoms than in others. So, this is telling us something about the immune system.

But there are other signals that point to the nervous system. Indeed, one signal, on chromosome 17, CA10, had previously been found among people experiencing chronic pain. So, these are signals that absolutely align with how you - people with ME - have described your illness, your symptoms. What is happening here is that the DNA, your DNA, is speaking back to us as researchers exactly how you have described your symptoms, such as chronic pain.

When we studied the genetics of ME, we did so in part by separating females from males, and we found no evidence in this analysis that there was a sex bias at any of these 8 signals.

Next, we asked our international colleagues whether they could look at the results that they have in their independent data to see whether what we have seen in DecodeME, that they also could see. In other words, whether it was replicated in their data. So, for the 8 signals, half of them, four, had modest statistical replication, this wasn't strong in the data from different biobanks - from the UK Biobank and the Netherlands Lifelines Biobank. Nevertheless, even though these were modest, they were far more replications than would be expected merely by chance.

So, we can say that there is a degree of replication in external data, and we also found that two of the signals in females were statistically significant when tested in males. So, there's good degree of replication, and we would expect these signals to be found again, in independent studies.

Importantly, we now need to answer some of the questions that you have and these are some questions that have been posed on social media and elsewhere. So, what do these results that we've just shown mean for people with ME, for you? What do they mean in particular for families?

Now, we already know from other studies that having ME yourself makes it twice as likely that a first or second or even a third-degree relative would also have ME. But even so, the doubling of risk only goes from a 1% chance to a 2% chance. So overall, this change in risk doesn't greatly affect the chance that someone will have ME, just because a family member has it. Okay, so genetics here is not being deterministic. It's not determining that someone will or will not have ME. 

That speaks to the second question, which is, does having one or more of these eight genetic differences mean that someone will have ME? The answer is no, not at all. The genetic signals that DecodeME has discovered, these are not diagnostic. They cannot tell whether or not someone has ME, and also, we need to say that diagnosis is up to healthcare professionals.

If DecodeME had found that there was this single genetic signal in one gene that clearly caused ME, then this signal would, in time, become diagnostic, and that would be like genetic variants in breast cancer, for example, or cystic fibrosis. But ME, we know now, has lots of genetic signals, and each of them is small, they're not of large effect, so they do not diagnose individuals.

Rather, we need to say that there are chances of getting ME that are affected by four things. There are the genetic signals that we have discovered, there are genetic signals that remain to be discovered in the future - different studies, larger studies - and importantly, the third thing is not genetics, these are the non-genetic influences that exist in the environment. You'll know these as exposure to viruses or bacteria, for example. And then the fourth and last thing, is how genes and the environment interact. 

The next question is that if someone doesn’t carry the genes, does this mean that they won't get ME? So, no. The eight signals, they also can't say that someone won't get ME, because of these other three things I've just said. The genetics we couldn't see, the environment that we're not testing, and how the genes and the environment interact.

The fourth question is does this mean that ME is a life sentence, and that someone won't get better? Given what I've said, hopefully it's clear that these genetic signals are not perfect predictors of disease or non-disease - they're not able to say anything about recovery, for that, we would have needed to have done a GWAS on recovery, on those who have or have not recovered. 

The next question is, what does it mean for treatment and testing? Unfortunately, it doesn't mean anything immediately. We always said that DecodeME was about establishing a firm foundation of evidence upon which we and others can build. Or using another analogy that we've been using, DecodeME marks the spots, the X's, where evidence for future treatments and testing needs to be found if only scientists worldwide could dig for the treasure that exists there.

What does it mean for other co-occurring conditions, like fibromyalgia? Well, in time DecodeME will do a GWAS, a genome-wide association study, of those with both ME and fibromyalgia against the general population and hopefully that will also shed light on fibromyalgia, as well as ME.

So, the penultimate question is about if someone was a participant, would it mean that they definitely have one or more of these genetic differences? No, DecodeME is all about discovering the genetics of everyone, the set of 18,000 people with ME, and it is not about the genetics of any one person. Therefore, it can't help today, anyway, with that one person's treatment or diagnosis. What DecodeME is about, it's about you all together, it's about you as a community. It's about everyone who shares your genetic variants and has ME. It's not about separate individuals and having ME does not mean that you have or don’t have these genetic differences.

Lastly, someone often might ask whether they can receive their individual genetic results back from DecodeME. I'll just read back what we had said to you in our participant information sheet at the beginning when you gave your consent, that we won't give any information back to you about your genetic findings. And an important reason why not is because these results cannot be used for diagnosis or treatment, and they could easily be over-interpreted and that over-interpretation could cause harm.

And so, we took the decision, I think it's the right one, that we would not return results, in particular because those results do not mean anything for treatment.

ANDYHello to everyone. Leading up to this webinar, I was pondering about the best wording to try and describe the response that we've had to our results, and I can't find the right word for it. For you, and for us, it's been an amazing response. The coverage has been worldwide, obviously it has meant much coverage in the UK, but the coverage is extended to the states, to many other English-speaking places, but also to, I'm aware of Belgium, France and other places on the continent. 

As our bullet point covers, the second bullet point, the tone of that coverage has significantly shifted. This was my very first time, well when we announced the results at the press briefing, that was my first press briefing ever, but obviously first linked to ME coverage too, I noticed that all of the journalists there were focused on the biological results, on the genetic results. There was no exploration of other facets that have been asked about previously. It was just focused on the genetic results and additionally, how that might impact those of you out there, the ME/CFS community. 

So, it was lovely to see, and obviously, what was lovely to see as well was the community response. We had high hopes for what the reaction and the coverage might be, and it's safe to say that both of those things have far exceeded what we were hoping for. So, you know, thank you for your reception of that coverage of the result of our hard work. It means a lot to us, and we have seen how much it means to you. To cover the final bullet point, if I can just briefly hand back to Chris to cover what scientific response we've got as well.

CHRIS

Thank you, Andy. I've heard from many scientists and researchers with congratulations for the whole team, and great appreciation that thankfully, and finally, a genome-wide association study has been now applied to ME, after all these years when it could and definitely should have been applied.

The scientific response, I think, is best reflected by the 42 times that people around the world who are scientists have, and others, have downloaded the summary statistics. So, these are essentially the data underlying the Manhattan plots - people now around the world freely can gain access to these statistics that are not about individuals, they're about, in general, the ME population, and they can investigate ME genetics for themselves. We've heard from the Open Medicine Foundation with their congratulations and we've also heard from many other researchers.

So, what's next? Well, not just us in DecodeME, but others around the world, now will need to build on the foundation that DecodeME has provided. Of course, our next goal is to complete all of the analyses that we wrote up in the data analysis plan, and of course, we will submit to a journal for peer review, that will come in time. But through data dissemination, this is a rich data set and it will live on.

86% of people who are participants in DecodeME have consented to sharing their data, and 95% have consented to being recontacted for new projects.

What is required, and I'm going to bring in Sonya in a minute, are highly targeted studies by scientists around the world who have expertise in all of these different areas that are now relevant, into why each of these 8 signals is linked to ME, and that's important because we can and should move quickly towards future diagnostics and treatments. Sonya, over to you.

SONYA

Thanks, Chris. Okay, so technically we're due to finish the DecodeME study at the end of August, so it will finish in its current form and the team will shrink quite substantially in size. But we do want to continue where we can, and several of us will stay involved. We want to analyse the second questionnaire data, we need to finish a small study on the impact of people with lived experience involvement, and also, we want to do more in terms of the genetic analysis.

So, you will see things coming out, and we will consider how to ensure we maintain communication, but the website itself will be moving over to the University of Edinburgh, so that we can maintain it, and you can still access all of the information there. We've had several questions about the recording of this presentation and the Q&A, that will be available for you as soon as we can get that up, and we will let you know where you can find it. It will be on the DecodeME website, hopefully within the next week or so but then everything will transfer across to Edinburgh. Most of our communication channels will close down as we just don't have the team in place anymore.

However, we want to reassure you that your data will continue to be safely stored at Edinburgh University, and one of the questions that's come in is around whether the data is held anonymously. It absolutely is, and you can read more about that on the website under the FAQ, and also in the information that you will have received when you first took part.

So, we will continue, and the patient public involvement, the PPI team, will continue, and we will keep you as updated as possible. And one thing I would suggest is that you sign up to Action for ME's newsletter, because we will use that as a communication channel when we have got something to say. We will also make sure that we put things out on social media as well as on the web page. 

We are already thinking about the what next and we've been thinking about the what next almost from the beginning, and we are currently fundraising for future studies. There is a link here if you want to support us with that, and thank you to the people that have already donated for Action for ME and Edinburgh University to continue our research work together, anything that is given through the DecodeME website will go to the two organisations and the PPI groups working together on biomedical research. 

We're also working together with Oxford Nanopore Technologies on a study called Sequence ME and Long Covid. We have not started that study, and Chris is going to say a little bit more about it in a moment. We did announce this, and you can find out more on the Action for ME, Edinburgh University and Oxford Nanopore Technology websites. We have got a partnership that is currently looking to raise the money that we need to be able to kickstart that study. This will use the DecodeMe data, where people have given their consent for us to be able to do a whole genome sequence study, and I know we've got several questions about that, so hopefully Chris can now answer some of those questions for you. Over to you, Chris.

CHRIS

Thank you. So, I said earlier that DecodeME is only finding some of the genetics. Sequence ME and Long Covid would find more of the genetics beyond what we've already found and that is because it's able to see things that DecodeME was never able and never designed to do, in large part because DecodeME does not look at the rare genetic variants that we all carry with us in our DNA, it was only supposed to look at common DNA variation.

And then secondly, there are large changes in our genomes called structural variations that are invisible to the DecodeME method but are not to the sequencing method. There is a third aspect, which is to do with DNA methylation, and that comes for free using the Oxford Nanopore Technologies approach of long-read whole genome sequencing. But the main key attributes for this study is that it will, if funded, provide far more precision as to which are the genes that contribute to ME risk, because we can intersect the genes that are affected by the rare variation, and the genes that have been indicated in DecodeMe, using the common variation and those two together should provide us with a greater degree of precision as to which of the genes are involved. 

So, who are we in Sequence ME and Long COVID? Well, you know who I am and the person in the middle is Professor Ewan Birney, who's a co-principal investigator on this who has been a long-term advisor for Oxford Nanopore Technologies and is a very eminent member of the genomics, genetics, and biological communities in Europe.

These organizations on the right, would be involved in the project, and we've set it all up and are hoping to attract funding. A substantial amount of funding is needed, we're talking millions of pounds, but we absolutely believe that it is worth it because of the DNA samples that you at sometimes at a great cost to yourselves have given us.

So, the last aspect, therefore, is all about modernization. We've talked about how the DecodeME study could have been done 15 years ago. This study, the whole genome sequence using this technology, has not been done at this scale for any disease, so this would be a remarkable achievement, if possible, to provide whole genome sequences for the DecodeME participants. And ultimately, we hope for all18,000 people who have kindly donated your DNA. So, thank you again, and we'll take questions now.

SONYA

Thank you, Chris. I’m joined on the panel by Chris and Andy as well, and so I will try and share the questions out, although there are a lot of questions around the genetics. Just a couple of things to say in response to questions. We were asked how many data access requests there have been, so that's other scientists wanting to access the anonymized data to be able to undertake research, and we've had 9 thus far. We are really encouraging more to come through and we look forward to hearing the output from those researchers' research as well. So, already, those of you who participated are helping other research, and just a reminder, that this is all anonymous for you. 

I do want to just acknowledge our funders, the Medical Research Council, the MRC, and the NIHR and say thank you to them as well.

Chris, I'm going to start with a question for you. I'm wondering how the hypothesis for this study came about, were there previous smaller studies that suggested these genetic signals might be found?

CHRIS

There were not previous studies that have suggested these genetic associations. The previous studies that have been done, we have not replicated their findings and either that's because we are looking at a different subset of people with different symptoms, or the other studies were not sufficiently powered to find things that are replicable. Where does this approach come from? The genetic approach is important and has been applied to essentially all other conditions, and until now, not ME. Because it gives insight into cause and not downstream consequence of disease, the associations that are found are nowadays almost essential for drug companies to follow up on the particular leads that they are pursuing for drugs and treatments. And we know that genetic evidence more than doubles the likelihood of a successful development of a drug all the way through to the clinic, so genetics now is firmly established as being essential to provide effective treatments. So, we knew that then, and that since has been very much consolidated. And so our tasks now are to accelerate into that arena where the pharmaceutical companies are made well aware of what we're doing and well aware of the results, and they pick up on leads and they follow them through to completion. 

SONYA 

Thanks, Chris. We've got a question from Niamh, who's asked if there's a way of getting involved in future research as a researcher. So, one of the things I was going to highlight a bit later is that we have been successful in securing funding for a project called PRIME. It's about building infrastructure, it's not actually undertaking research, but creating new collaborations to stimulate more research, and ensuring that people with lived experience are completely embedded in that research. So, there will be more information about that. That launches in October and there's also a stakeholder event that the NIHR is going to be organizing in the autumn, that was one of the actions in the government delivery plan.

So, Niamh, if you want to give details, and if we've got other researchers in the audience that want to be involved, please send your details in to the team. You can do that through the website. There's a contact address, we'll capture that and make sure that the NIHR put you on the invite list.

Chris, back to you again. Is there a link with protein growth internally and ME?

CHRIS

In my reading of what the genes do, and what the proteins do that have been linked in these 8 signals, I have not seen any specific link to protein growth. There are many other aspects of cellular biology that are possible and are one of many explanations for people's ME symptoms. What we tried to do, a little bit in the main manuscript, but also, in an accompanying manuscript, is to look through what is already known for these proteins and genes and to say, in a very simplified way and condensed form, what might be the explanations through these different genes. But I don't remember protein growth being one of them.

SONYA

Thanks, Chris, and apologies, everybody, if I'm looking the other way at times, because I'm following all the questions that are coming in. It's not that I'm doing my emails or being distracted. So again, Chris, we've got quite a lot of questions here around epigenetics and sort of what can influence genes and what the impact of life events and other things might have. I know you touched on that, but can you just say a little bit more for people?

CHRIS

Yes, so anything that has happened since birth that might have modified your DNA through methylation, which is a chemical modification, this is not being considered in DecodeME, but, interestingly, it would be considered in SequenceME and Long COVID. If people are interested in genetic activity, gene activity, and this is different in different places in the body, we have done that analysis for Figure 4, because what that intends to show is whether there is an agreement between the genetics of gene activity and the genetics of ME. If they align for a gene in a particular tissue, then we have shown that they align, they are concordant, they are so-called co-localizing. So, we are considering gene activity if that is what people are meaning by epigenetics.

SONYA

Thank you, Chris. We've got lots of questions around whether GPs will be told about these results?

As Andy referenced, we had huge coverage, and I know many, many GPs and others have seen the results. We are not going to be writing directly to GPs, that's actually a huge task to do, and you have to buy databases and all of that kind of thing. But one thing that you can do is to take the results into your doctor's surgery and share them. The other thing that Action for ME will be doing is liaising with those who developed the e-learning, which was another action within the delivery plan, to ask how the e-learning will ensure it integrates the results from DecodeME, not just these results, but also what we find later on, so we will definitely be doing that.

Given that more and more people are developing Long Covid by the day, if funding was available, would we as a team reopen the call for Long Covid samples so they could do the research with a bigger, Long Covid cohort? 

We did actually apply to do this, and we were not successful for funding. If funding was available, then absolutely we would want to do as much as we can to maximise the insight, if it was appropriate for us at that point in time, but as we've said, SequenceME and Long Covid will obviously include the Long Covid cohort. 

Chris, could you give us examples, one or two examples of other GWAS, genome-wide association studies, that have led to meaningful change, treatment and understanding for those with the disease?

CHRIS

Sure. During the early stages of the COVID pandemic, there were no effective treatments for acute COVID. So this is for people who were in difficult, really desperate situations in hospitals. And my colleague at the University of Edinburgh, Kenny Bailey, led on a genome-wide association study for acute COVID and found many places around the genome that had genetic signals for acute COVID. One of them contained a gene for which there was and is known an inhibitor against its protein and that inhibitor is called baracitinib. And immediately, as that was realized, that was included in a trial within months and was then shown to be effective at reducing mortality. It saved lives. So that, to me, is one of the best examples of how genetics has had a direct influence on medical practice. 

SONYA 

Thanks, Chris. We've got lots of questions I'm going to try and pull together around percentages of people that showed the 8 identified genes in the sample group and the control group, and the level of granularity that people might want to be able to access. So can you just repeat some of the things that you've said just to highlight that.

CHRIS

Yeah, I mean, this is something that I don't think I've done very well in conveying, so my apologies for this. Anyone who doesn't have any of the signals or anyone who does have all of the signals, is not predetermined to have ME or not. This isn't what we're looking at. So, this begs the question, and it's a really important question, why on earth are we doing this if it's not relevant to individuals? And what we're trying to say is how relevant it is to the population of people with ME, and what these signals show is where to intervene, where there are genes that in the future, where there are interventions that involve those genes, they will have an effect on people's ME symptoms.

And just because the GWAS signal has a small effect on whether someone has ME or not, and here we're talking about people with ME, you might have 13% of people who have the genetic variant, and only 12% in the general population. That 1% is what's giving us the significance. And you, probably quite rightly, are saying, well, hang on, that's not a great difference, but the genetic difference does not, and we know this, the genetic difference does not predict how effective the drug will be.

If the drug were to be found against the gene implicated by that signal, then that could have a very large effect. So, the genetics tweaks things, it tells us where to go in and intervene, and a drug will go in like a hammer on a nut, whereas the genetics only looks for small tweaks. And hopefully that's described a little better now.

SONYA

Thanks, Chris. We've got a question around whether AI was involved in this process at all, and I think this might be an opportunity maybe to say a little bit about the declustering work that we're doing in partnership, but also maybe touch on LOCOME, because we've got lots of questions around what we're doing there and what we might find. Both of those studies are using the DecodeME data, so maybe you could just say a little bit about that? 

CHRIS 

Thank you. Yeah, I mean, this is a big data study. I think that's clear. The algorithm that we used, Regenie, that is formerly a machine learning approach but what you've just said is absolutely right. In our partnership with Precision Life, they are an AI company, and they are deploying approaches that we are not using, and they have the consented and anonymized DecodeME data, and are actively analyzing it in this co-produced project called LOCOME that Sonya has mentioned.

We will go out and talk to any company ensuring that they are well aware of the predictive potential of the of the data set. And one such group of people at Hartree near Warrington came to us, and we are now working with them for clustering of both the questionnaire responses and the genetics, and that is becoming quite, quite interesting.

SONYA

Thanks, Chris. Andy, I'm going to come to you. Are these study results, what you expected?

ANDY

It's in line with what I hoped for. But obviously genetics is, as I have learned, particularly learnt over time with Chris continuing to hammer the knowledge into my poor little brain, helping me to understand.

It's kind of what we hoped for, and we suspected we might find results like this, but I think it's fair, to be precise to say, that we didn't expect to find precisely what we have because really there was no… while the results suggest that, strongly suggests that things are in line with patient reports, there was no kind of obvious link the other way. So, it was not really possible to say that because the patients report this, that therefore this, and the other particular gene, was involved. So sorry for a longer answer than perhaps the question invited, but certainly we hoped, obviously, to find something, we suspected that we would find something, but we didn't have specific findings that we were expecting to find. And Chris will now correct me in case I've said anything wrong there.

SONYA

From my perspective, I was also really hopeful, like you, Andy, but as Chris kept saying to us, we may find nothing, and we know that getting a null result is also important data. But we're not in that position, so, it's great that we've been able to identify what we have, and we hope that we will continue to find more. Andy, I'm going to ask you another question. Can you remind us what the second questionnaire is about, or was about?

ANDY

Many things. It was about broadening our understanding of our patient population or the cohort from the patient population. So, really it was just asking for more detail on what our participants experience and I'm now struggling to remember exact examples, apologies, but we were talking about pain, exact descriptions, we went into more detail on post-exertional malaise, treatments that people had tried, and what they reported as being useful or not, so it was broadening even more the level of detail that we have on the cohort, so speaking to researchers out there, we have even more information about our cohort that can be used to investigate ME/CFS further. But apologies, I can't at the moment reel off a list of what we looked at, but it was to ask our participants what they experienced, what was basically important to them, which was not covered in the first questionnaire. So, hopefully that gives a good overview.

SONYA

Again, and I say this without knowing definitively, but I suspect the questionnaire will be available whether it's through our website or elsewhere, but we will be sharing lots more information and results from our analysis of that in due course. And we had a question around how this links with the government's new ME strategy, so I'll just pick that one up.

DecodeME’s funding was secured through application, through a specific fund that was set aside to undertake genetic analysis that doesn't relate in any way to the government's strategy, and clearly the results came out after the delivery plan was launched. However, many of us are working to ensure that the delivery plan is now implemented and we are calling for a more strategic approach to research funding, and many of you will have seen the information that we shared on the priority setting partnership website, and hopefully one of my colleagues can pop it in the chat for you, so you can have a look at that website and see who's been working together and what we've been calling for, and so that information is there. Chris, I just wonder whether you can say something around whether DecodeME suggests subgroups within ME, what we were looking to find and not looking to in the study, and where the research may go now in terms of subsetting.

CHRIS

Thank you. We did not find any difference between females and males, we've covered that, so, that's not the subset. We have not yet analyzed with respect to any differences across severity scales and when we looked at the infection at onset versus non-infection at onset, there was a change in this one genetic signal, OLFM4 but, essentially, no other significant change.

We want to look at stratification. We know because the genetic results tell us that ME is a complex disease, we know that there are different strata, different ways in which the people can be separated. Our colleagues at Precision Life will always tell us that they are able to predict different subsets of individuals and we'll be listening to them to see whether that plays through with their clinical trials that are ongoing. So, I can't tell you today that we have found different subsets, but I do believe that they exist.

And in the Sequence ME and Long COVID project, what is undoubtedly going to happen, if funded, is that we will be able to find individuals whose symptoms can be explained by very rare conditions where the symptoms match and mirror what is in ME, but are better explained by other rare diseases.

SONYA

Thanks, Chris. We've got questions around Sequence ME and Long COVID, and how long that's going to take. I just want to reiterate, we have not yet got the funding that we need to be able to start that study. It is going to take millions of pounds to be able to deliver the whole study. We're looking at 9,000 people with ME, using the samples and DNA data that we've got already, and therefore that will be much quicker, but we would need to recruit the 9,000 people we needed for the Long COVID whole genome sequencing. So it's not going to be immediate, we've got to get the funding in, and then we will look to start that study, but it is not going to happen immediately. 

We've had questions about who's involved in the DecodeME team, please do go to the website. We've got the frequently asked questions and there's lots and lots of information there and I've deliberately not picked questions that we answer already on the website.

I'm really conscious that we've only got a couple of minutes left. So, I want to ask both Andy and Chris, what your hope is now in terms of the research, and, what's the thing you're most proud of, being involved with the DecodeME study? So maybe Chris first.

CHRIS

I think the thing that I'm most proud of is that I've been told that people with ME have sat with their families and friends hearing about the results, and those people with ME have been understood better because of the results.

SONYA

And anything you hope for next?

CHRIS

I hope that life is just made easier, both in society, in the health system and in future research by what is only, and I wish it was more, but only the first step, and we just have to try and make sure many other steps are taken soon by many people. It is clear that ME is not a research priority for this UK government. Other diseases have been a priority for previous UK governments, and we have to ask the question of them: Why is ME not a priority when all of these other diseases have been and are? Tell us why. 

SONYA

Thanks Chris. Andy.

ANDY

So, if it's not apparent to everyone, this is a curveball question that Sonya's just thrown at us, and me going second, Chris has obviously nabbed all the really good answers. I think there's two related things that I'm most proud of. DecodeME has had such an obvious level of trust with the community and through an awful lot of behind-the-scenes work, we seem to have kept that trust through to this point, and hopefully you'll stick with us to when we publish results, and perhaps into future projects as well. And the second point is that I'm proud that we as a patient community has been able to put down the lie that we are basically anti-science, whatever description you want to use, in the level of support and interaction, and involvement with our study shows that the patient community just wants research. You… you're all out there, desperate, as I am for investigation into this horrible disease that ruins lives. And you want answers, and you want treatments, and you want diagnostics. And you're here with us in attempting to achieve all of that, and it's the community and the patient community and the research community working together. So, it's never been true that the patient community has been anti-science and DecodeME is a shining example of that. Sorry, what was the other part? I kind of went off on one there.

SONYA

I think that's all right, Andy, I think you did a great job. I love throwing curveballs at my colleagues, it keeps them on their toes, and they certainly do that back at times, too. So, I'm not going to repeat anything that's been said, everything that Chris and Andy says totally chimes for me, too. I couldn't be more proud of what we've achieved as a team. We are a much wider team, there are many people working behind the scenes in the labs, responding to emails, helping set up this webinar, all of the different roles and I think I will bring it back to the team, given we're just about to wrap up, and acknowledge the incredible work that they have done and the level of challenges that we have had to overcome. Many we foresaw, and many we didn't, and I do think it has been a really remarkable journey, and at the heart of it has been you, people with ME, and many of us on the team have our own personal experiences with ME, so it matters to us as well as mattering to you. 

And, as I said at the beginning, we've been overwhelmed by the comments and the responses and that's borne out again in all the comments, not just in the questions, but people just saying, thank you. But we want to say thank you to you for your energy, your commitment, your belief in us, and your trust in us, and we will continue to do as much as we can to accelerate research, because we all deserve it, regardless of whether it is a governmental priority or not. I also just want to say thank you to our scientific advisory board, who have been with us throughout this journey challenging us to do even better than we were doing. They played a very valuable part. 

So, thank you again for your time. The recording will be available afterwards. We will let you know when it's there. And just a reminder that our communication channels, as DecodeME study will close right down. So please do understand, we're not going to be able to respond to individual contact as much as we'd like to, we've got to focus on getting the rest of the analysis out and hopefully having as big an impact as we have done this time. Thank you very much.