1. Guest, 'News in Brief' for the week beginning 17th February 2020 - click here.
    Dismiss Notice
  2. Welcome! To read the Core Purpose and Values of our forum, click here.
    Dismiss Notice

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

Discussion in 'BioMedical ME/CFS News' started by Andy, Dec 18, 2019.

  1. Adrian

    Adrian Administrator

    Messages:
    4,340
    Likes Received:
    21,307
    Location:
    UK

    I think there is value in that this cohort could be used to help select smaller sets. This may be particularly the case if there are potential subtypes due to different genes which could lead to researching into different mechanisms.

    Or be used for epidemiology studies (such as the one norwegen one that looked at what age people were first ill).
     
    Milo, Trish, Andy and 2 others like this.
  2. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

    Messages:
    6,224
    Likes Received:
    63,103
    The key problem is denominators. I had significant reservations about using any population recruited through the internet for any purpose originally but I was persuaded that for this particular task an internet based sample, if it was big enough, would be of value. For most other studies where you need large numbers I think the denominators need to be known. Certainly for an epidemiological study you need to know the size of population you are sampling from and the weighting in sampling.

    It is a common misconception that gathering cohorts for one study will help with all sorts of other studies. The King's Twin Project is maybe an unusual example where it makes sense, since genetic studies of almost anything can use twins.

    I agree that it seems a pity not to make use of people who have already volunteered, but privacy and other issues come so high on the agenda that I think it should be a very secondary consideration. It is unlikely that a sample of this size is going to be needed again. Most spin off physiological studies would need no more than 100 individuals. If 5,000 show interest within a fortnight for this then re-finding 100 should not be so hard.
     
  3. JemPD

    JemPD Senior Member (Voting Rights)

    Messages:
    988
    Likes Received:
    8,214
    Agreed.
    What would be truly terrible is if we were unable to recruit sufficient numbers for this study because of privacy concerns introduced due to enthusiasm for the possibility of other, as yet unknown, unspecified & unplanned studies. ISTM that the critical thing is to ensure we get enough numbers to make this study viable. 25,000 people to volunteer is going to be a huge ask & we need to be careful that we don't sacrifice the number one goal for the sake of goals 2,3,4 whatever.

    I know BPSers will likely take the finished anonymised data - eg 'X% of PwME have xyz gene', & twist it to mean whatever they want. Cant do much about that & an acceptable risk for the possible gain I think. But if there is any chance of them getting their hands on my saliva and or my name & contact details, then I wouldn't feel safe to participate.
     
    Hutan, MEMarge, MSEsperanza and 4 others like this.
  4. Sarah94

    Sarah94 Senior Member (Voting Rights)

    Messages:
    1,741
    Likes Received:
    5,052
    Location:
    UK
    In an ME facebook group that I'm in, somebody has asked "why can't they use the raw data from the DNA tests that some of us have already paid for? The OMF does." How should I answer that? I know why not, but can't think how to articulate it... damn brain fog.
     
    MSEsperanza, Kitty and TrixieStix like this.
  5. Amw66

    Amw66 Senior Member (Voting Rights)

    Messages:
    3,104
    Likes Received:
    14,791

    Data varies as chip versions have changed over time and so gene content has changed

    May not have particular Gene's as most are selective ( unless you have a full genome) .

    OMF do not use 23andme which is probably the widest consumer accessible provider. ( photo posted last year showed gene kits on a desk and i' m sure that they were not 23andme)

    Klimas has I think and some of the papers published have been discussed here. Beyond my knowledge, but people don't seem to have been impressed.
     
  6. TrixieStix

    TrixieStix Senior Member (Voting Rights)

    Messages:
    165
    Likes Received:
    1,212
    I would imagine the fact that consumer DNA tests are thought to misread & misreport a not insignificant number of SNPs would also be a barrier.
     
  7. Andy

    Andy Committee Member & Outreach

    Messages:
    8,641
    Likes Received:
    62,729
    Location:
    Hampshire, UK
    A general reply regarding some of the latest issues/concerns raised in this thread - I don't think it is practical reply to each post individually.

    I think that the issues raised (including concerns about consent/data sharing/re-contacting, validity of the planned large re-contactable cohort, and the question of using commercial genetic testing) are probably best addressed by the actual scientists. However, there will be a delay on this, as a lot of work, mainly by them, is currently going into writing, amending, re-writing, correcting and re-re-writing, the application for funding, so I would ask for everybodies patience at this time - good questions have been asked, valid points have been raised, and we will address them, but we need to focus on the application first, at this time.
     
  8. JemPD

    JemPD Senior Member (Voting Rights)

    Messages:
    988
    Likes Received:
    8,214
    Happy to see them prioritising @Andy :) happy to be patient.

    please confer gratitude & encouragement to them
     
  9. rvallee

    rvallee Senior Member (Voting Rights)

    Messages:
    3,309
    Likes Received:
    25,033
    Location:
    Canada
    Those are only partial tests, which is why they are cheaper than a full genome reading. They only look at genes known to be significant in some diseases, when the purpose here is to find among all the genes which ones are significant to ME.
     
    TrixieStix, Hutan, Natalie and 4 others like this.
  10. InitialConditions

    InitialConditions Senior Member (Voting Rights)

    Messages:
    287
    Likes Received:
    1,683
    Location:
    North-west England
    The whole process needs to be standardized too - you can't just bring together data from different tests.
     
    TrixieStix, MerryB, Michelle and 5 others like this.
  11. Andy

    Andy Committee Member & Outreach

    Messages:
    8,641
    Likes Received:
    62,729
    Location:
    Hampshire, UK
    Update: the FAQ has been revised and reorganised, https://mebiomed.org.uk/faqs/

    As always, if you spot anything that you believe is incorrect and/or have suggestions on how it could be improved then please let us know.
     
  12. Robert 1973

    Robert 1973 Senior Member (Voting Rights)

    Messages:
    480
    Likes Received:
    6,044
    Location:
    UK
    From the FAQs:
    I don’t understand why people who have recovered aren’t being included. Understanding why some people seem to recover and others do not is hugely important. Presumably, it could be that some people have genes which increase the probability of recovery, or it could be that the people who recover have a different illness or a different type of the same illness. I would have thought that these are exactly the sort of questions that a GWAS could answer.

    I understand the need to recruit a minimum number of participants who fulfil the CCC or IOM diagnostic criteria, but I don’t understand why an additional group of recovered patients couldn’t be included. Is it a cost issue, or is there another reason for the decision? Is it too late to change the proposed design?

    It would be frustrating if the GWAS managed to identify distinct sub-groups but was unable to tell us whether any of those sub-groups were more or less likely to recover or significantly improve in time, without treatment.


    NB I’ve not managed to follow all the discussions, so apologies if this has already been discussed. If it has, please can someone post a link? Thanks.
     
  13. strategist

    strategist Senior Member (Voting Rights)

    Messages:
    2,386
    Likes Received:
    23,264
    Maybe there are concerns about the reliability of retrospectively applied diagnoses.
     
    TrixieStix, Sarah94, MEMarge and 7 others like this.
  14. Robert 1973

    Robert 1973 Senior Member (Voting Rights)

    Messages:
    480
    Likes Received:
    6,044
    Location:
    UK
    I guess there may be but presumably there will be concerns about the reliability of current diagnoses too – or rather, the reliability of the answers to questions which are used to determine whether or not someone fulfils the diagnostic criteria.

    I assume that answering questions about historic symptoms is likely to be a bit less reliable than answering questions about current symptoms but I don’t know how much that would matter. My limited understanding is that for a GWAS it doesn’t particularly matter how many unreliable diagnoses there are, provided there are sufficient numbers of reliable diagnoses (however a reliable diagnosis is defined).

    Also, let’s assume that a separate, additional cohort of recovered patients is recruited – people who have previously been diagnosed with ME/CFS, whose answers to questions about their symptoms prior to recovery meet the study’s criteria for a diagnosis of ME/CFS. Now let’s assume that the GWAS identifies a number of SNPs that are significantly more common in people who currently meet the ME/CFS diagnostic criteria than in the healthy controls. Whether or not those SNPs are equally common in the recovered cohort would tell us something useful about people who report that they have recovered from ME/CFS, regardless of how reliable their answers are. And that is something I would be very interested to know.

    Having said that, looking at the number of likes that my comment has received compared to strategist’s reply I’m wondering if I’m misunderstanding something.
     
  15. ringding

    ringding Senior Member (Voting Rights)

    Messages:
    280
    Likes Received:
    2,056
    Location:
    Bristol, UK
    I wouldn't read too much into numbers of likes.
    Just over a year ago I'd have been in the "almost recovered" category. Now I'm most definitely ill. I'm also not sure of why the "phasing" of symptoms, if remitting/relapsing, should impact on suitability for inclusion. Is anyone ever really recovered?
    Surely if someone has had ME of any severity their genetic information would be of use?
     
  16. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

    Messages:
    6,224
    Likes Received:
    63,103
    I don't understand why the questionnaire cannot ask whether either now or in the past the person has fulfilled the various criteria.

    CCC and IOM criteria do not have to be applied in the present tense. They remain the same criteria applied in the past tense.

    The past might actually be more reliable than the present since PWME may well not know exactly how things are in the present if they are pacing effectively.
     
    Invisible Woman, Barry, Hutan and 3 others like this.
  17. Sisyphus

    Sisyphus Senior Member (Voting Rights)

    Messages:
    302
    Likes Received:
    1,067
    “PWME may well not know exactly how things are in the present if they are pacing effectively.”

    There’s a substantial amount of significance in this one sentence. i) I have learned, at considerable cost, that feeling better for a month does not mean I am either free of or safe from the disease. ii) not only pacing of activity, but unknown factors which may relax for a time may give one a partial respite. That improvement comes to a crashing end not only from over-activity but from some trivial stressor (heat, a common cold, sleep disruption, etc) or for no observable reason. There are certainly unknown body processes involved, there could be stochastic processes triggering a relapse.
     
  18. Snow Leopard

    Snow Leopard Senior Member (Voting Rights)

    Messages:
    1,508
    Likes Received:
    8,931
    Location:
    Australia
    Agreed, this seems like a serious oversight. Those in remission are a notable subset.
     
    Robert 1973, JohnM and MSEsperanza like this.
  19. Amw66

    Amw66 Senior Member (Voting Rights)

    Messages:
    3,104
    Likes Received:
    14,791
    If this is, as multiple reports suggest, a relapsing and remitting condition, then " recovered" genetic info may play an important role.
     
    rvallee and MSEsperanza like this.
  20. MSEsperanza

    MSEsperanza Senior Member (Voting Rights)

    Messages:
    994
    Likes Received:
    7,016
    Location:
    betwixt and between
    I think it could be very helpful if someone were able to answer the concerns expressed in the comments on the Virology Blog article, in particular provide more details about the diagnostic / selection criteria.

    If these details aren't clear yet (according to the FAQ IOM or CCC or Fukuda (*) will be used), perhaps it could be added to the FAQ (explicitly at each question regarding diagnosis) that he project team is still working on this, incorporating feedback, also on how to ensure that PEM isn't understood as just feeling bad after exertion.

    (*) [edit: this has now been answered, they just forgot to remove Fukuda in the FAQ update (Q: "What case definitions will be used?") see Andy's reply.]


    Q: "How will the study ensure...participants really do have ME/CFS?"
    • "We take diagnosis very seriously. You will be diagnosed using the CureME patient questionnaire that has been in use for the UK ME/CFS Biobank for several years."
    It seems the questionnaire isn't available on the CureME website. Is this intended?

    • "a GWAS does not need 100% diagnostic accuracy to produce valid results."
    This seems a very relevant info. I think it would be good to link to a source that explains why.

    • "as part of the study, some patients will have an assessment by a clinician with knowledge of ME/CFS to confirm the diagnosis is accurate".
    Could be re-assuring to know what percentage of participants is intended to be assessed by a clinician and how this will be done (selection, home visits?).

    (And don't know but perhaps better to write "participants" instead of "patients"?)
     
    Last edited: Jan 15, 2020
    Sarah94 likes this.

Share This Page