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Significant association of DNA variants with self-reported ME/CFS (Chris Ponting blog)

Discussion in 'BioMedical ME/CFS News' started by Simon M, Aug 28, 2018.

  1. Chris Ponting

    Chris Ponting Established Member (Voting Rights)

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    All good points. A single, non-replicated, GWAS finding is not sufficient - I agree. This is why my personal point of view is that a well-powered GWAS (with subsequent replications) is the first thing that is needed. Only then will causal hypotheses be generated, allowing findings to be "battle hardened" afterwards. The time-scale is long: probably 3-4 years. The cost is substantial: probably £3m. But in my view (and those of others) this is the quickest approach for generating causal hypotheses that can then be followed up.
    With respect to this single observation from the Neale GWAS, I am more convinced than you are because the same DNA variants that predict ME/CFS risk are also associated with altered level of the ornithine transporter gene. On this, I am really pleased that two researchers - one already working in ME/CFS, one not - have been in touch. One indicates that there is much unpublished data that *might* be consistent with the ornithine transporter hypothesis. The other works on mitochondria and we will discuss soon.
    I wish that all of this could have been done previously, by last Christmas, and the ones before that. I do not know how to go faster.
     
  2. Barry

    Barry Senior Member (Voting Rights)

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    I do very genuinely appreciate your sense of motivation.
     
  3. Trish

    Trish Moderator Staff Member

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    Would it be possible to do a replication study on this gene interval using the samples in the UK ME/CFS biobank?

    Could they be done concurrently? Surely it's worth seeing if the single region found replicates as well as doing a GWAS.

    Welcome to the forum, @Chris Ponting, and thank you for the work you are putting into trying to move this research forward.
     
  4. Guest 102

    Guest 102 Guest

    £3M - how I wish MRC was funding this kind of research instead of nonsense of PACE for £5M. It really was a crime they wasted all that money. I could weep forever. And thank you, Chris, for all you are doing.
     
  5. Amw66

    Amw66 Senior Member (Voting Rights)

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    Thinking of knock on effects and expressions ( and apologies in advance for lack if acience background)
    Both my aunt and daughter have genetic variants of genes regulating eNOS and glutathione. Being female, I' m guessing estrogen has an impact on modulation ?
    Would these be knock on effects of the ornithine ?
    I really need to seriously get into biochemistry - unfortunately going back to part time uni course may kick this into touch for a while.
     
  6. tuha

    tuha Established Member

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    In the past the patient's community was able to crowdfund for OMF (Davis research), Lipkins research several millions. Maybe it's worth to try it also for your research. Also if you can show to MRC/NIHR a certain amount of money from patients maybe they will be more forced/motivated to give the rest
     
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  7. Andy

    Andy Committee Member & Outreach

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    Random thought I had, several charities raised significant funds in anticipation of funding Rituximab studies I believe (MEA, IIME), does anybody know if they have been allocated to anything else?
     
  8. Sasha

    Sasha Senior Member (Voting Rights)

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    I may be wrong but I thought that the MEA didn't so much raise money specifically for a rtx study but ringfenced £60k of their existing funds if a study went ahead. I assume that money has been reabsorbed into the Ramsay Research Fund. IiME, of course, set up a separate fund and raised money for it. I think they ended up with over £400k. I thought they'd been spending it on B cell research at UCL with Jo Cambridge's team.

    @Russell Fleming, @Jonathan Edwards - is that accurate?
     
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  9. Sasha

    Sasha Senior Member (Voting Rights)

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    Profound vested self-interest on my part!

    I think we all agree that governments need to invest but our experience as patients - many of us over decades - is that governments don't invest in this. I hope that things are approaching a turning point but if the CMRC's application fails, I hope you'll consider tapping the ME charities for grants and initiating a project-specific crowdfund.
     
  10. obeat

    obeat Senior Member (Voting Rights)

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    There's also Jonathan Kerr's genetics study
     
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  11. wastwater

    wastwater Senior Member (Voting Rights)

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    Last edited: Oct 2, 2018
    andypants, adambeyoncelowe and ukxmrv like this.
  12. wastwater

    wastwater Senior Member (Voting Rights)

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    Saw his speech in Glasgow so thought I’d give this a bump

    (FOXO1 is next to The gene SLC25A15)
     
    Last edited: May 14, 2019
  13. wastwater

    wastwater Senior Member (Voting Rights)

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    SLC1A2 gets a mention at Stanford symposium
    SLC13A3 (a target of PITX2) is one I’m looking into linked to Axenfeld Rieger syndrome (hyperammonia mentioned) https://www.genecards.org/cgi-bin/carddisp.pl?gene=SLC13A3
    Another patient reported SLC16A1
    Another two reported SLC1A1(OCD/Autism/schizophrenia/glutamate)
    SLC25A15 mentions high ammonia
    Would that lead to high glutamine and high NMDA tired and wired presentation
    SLC25A33 pituitary FOXO1
    SLC1A1 https://www.omim.org/entry/133550
     
    Last edited: May 12, 2020
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  14. wastwater

    wastwater Senior Member (Voting Rights)

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    Last edited: Jul 14, 2020
    ukxmrv and merylg like this.

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