Julie Rehmeyer's 'Through the Shadowlands'
Writer Never Give Up talks about Julie Rehmeyer's new book "Through the Shadowlands: A Science Writer's Odyssey into an Illness Science Doesn't Understand" and shares an interview with Julie ...
Discuss the article on the Forums.

Analysis of data from 500k people in UK Biobank shows inherited component to ME/CFS (Ponting blog)

Discussion in 'General ME/CFS News' started by Simon, Jun 11, 2018.

  1. Simon

    Simon

    Messages:
    1,936
    Likes:
    14,646
    Monmouth, UK
    Guest blog by Professor Chris Ponting and colleagues at ME/CFS Research Review

    UK Biobank - a national biobank different from the ME/CFS biobank - has data from around 500,000 individuals, including both healthy people and those with one or more of the many different diseases in the UK population. About 2,000 people in the sample reported that they had been given a diagnosis of CFS.

    Analysis of data from this biobank indicates an inherited biological component for ME/CFS. The results show only one statistically significant change in a particular section of DNA and even this is problematic. This analysis indicates that a much bigger study, with many more ME/CFS cases, will be needed to indicate which genes and biological pathways are altered in people with ME/CFS.​


    [​IMG]
    Statistical significance for the association between each DNA position and ME/CFS across 22 chromosomes. The arrow highlights the one “significant hit”.​

    Introduction

    Myalgic encephalomyelitis (ME, also described as chronic fatigue syndrome, CFS) is a devastating long-term condition affecting 250,000 UK individuals. People with ME experience severe, disabling fatigue associated with post-exertional malaise. A few make good progress and may recover, while most others remain ill for years and may never recover. There is no known cause, or effective treatment for most. Consequently, it is vital to try new approaches to understand the reasons for the development of the condition.

    This blog sets out what we can glean from the release, last summer, of data from about 500,000 individuals who make up the UK Biobank. (This biobank is not to be confused with the UK ME/CFS Biobank, UKMEB.) The data were acquired from individuals between 40 and 69 years of age in 2006-2010 who live across the UK. These people provided samples (e.g. blood, urine and saliva) and answered questionnaires. In addition, for some of these people their electronic health record data are being linked in. Importantly for this blog, the DNA variation (‘genotype’) of all the volunteer participants has been determined.

    Genetic variation can provide insights into the causes of disease when these have a heritable component (i.e. are inherited down through the generations). DNA sequence is not altered by disease (except in cancer) and so variants can reveal the causes, rather than consequences, of disease.
    ....

    Read the full blog
     
    sb4, alkt, Mary and 10 others like this.
  2. melihtas

    melihtas Senior Member

    Messages:
    129
    Likes:
    366
    Istanbul Turkey
    My bolding;
    Dauer state??? Coincidence???
     
    sb4, TreePerson, FMMM1 and 2 others like this.
  3. Murph

    Murph :)

    Messages:
    823
    Likes:
    4,040
    If the prevalence of the genetic abnormality is .01 per cent and the prevalance of mecfs is 0.45% then this can't be more than a subset, right?

    If the genetic hit is for collagen, which is part of connective tissue, and the people self-report they have mecfs could these people be misdiagnosed EDS patients?

    Still, I'd like to hear more.
     
    sb4, alkt, Mary and 5 others like this.
  4. Simon

    Simon

    Messages:
    1,936
    Likes:
    14,646
    Monmouth, UK
    It’s complicated!

    Normally, it’s not as simple as one gene defect causes disease, particularly as people tend to get it later in life, rather than from birth.

    What these types of studies tend to throw up, I understand, is genes that individually have a small effect. Things get interesting when the genes affect one or a few biological pathways: different genes in different people could end up affect the same pathway, and that could point to a pathway playing a role. The pathway would then be the clue to follow up, rather than the individual genes.

    The problem is that this study is a small (compared with typical studies in this field) and it doesn’t have the statistical power to detect smaller differences , hence the point about a bigger study being much more useful. But these early results they suggest there is more to be found.

    Yes, lots of people have noted the EDS connection. But it’s probably too early to get excited about one particular hit, the evidence for genes in general playing a role is probably a more important conclusion.
     
    lafarfelue, voner, alkt and 3 others like this.
  5. alex3619

    alex3619 Senior Member

    Messages:
    12,854
    Likes:
    36,532
    Logan, Queensland, Australia
    Another confound here is that epigenetic changes can also be inherited, such as with smoking.
     
    anni66, alkt and ljimbo423 like this.
  6. FMMM1

    FMMM1 Senior Member

    Messages:
    174
    Likes:
    283
    Check out Neil McGregor's presentation at the OMF Community Symposium in September 2017. Neil presented data showing increased incidence of SNIPs in langerin and some other genes. This was a small study.

    Ron Davis is due to publish a small genetics study.

    Maybe these genetic studies will help to establish a mechanism/diagnostic markers etc.
     
    alkt likes this.
  7. FMMM1

    FMMM1 Senior Member

    Messages:
    174
    Likes:
    283
    Way out of my understanding but I assumed/guessed that if a gene is found in other species (such as a naematode) then it would be described as conserved rather than not conserved (sorry quotation marks not working).
     
    alkt likes this.
  8. alex3619

    alex3619 Senior Member

    Messages:
    12,854
    Likes:
    36,532
    Logan, Queensland, Australia
    My interpretation is not that that the gene is not conserved, its this region of the gene that is not conserved. That is it has high variation. What I am unsure of is why they say this part of the protein is not conserved. Proteins are several steps away from the gene and subject to their own variations due to post gene processing. If the gene is not conserved then it follows the protein may not be conserved ... may, not is. It depends on the variations.
     
    Last edited: Jun 11, 2018
    sb4 and FMMM1 like this.
  9. FMMM1

    FMMM1 Senior Member

    Messages:
    174
    Likes:
    283

    Thank you very much for your explanation.

    So they've discovered a potential variation in the gene in people with ME/CFS [i.e.at the 124th amino acid position].

    Weirdly the variation discovered in people with ME/CFS changes the gene to the form found in a nematode worm [i.e. at the 124th amino acid position]. See melihtas's comments above. Also, Naviaux proposed that ME/CFS is similar to the Dauer state found in nematode worms.

    I wonder what the protein does; i.e. do we know its function in humans/is it related to the Dauer state found in nematode worms?
     
    sb4 likes this.
  10. alex3619

    alex3619 Senior Member

    Messages:
    12,854
    Likes:
    36,532
    Logan, Queensland, Australia
    This is interesting, and probably should be investigated, but its most likely coincidence. I am sure that patients share many coincidental match-ups with nematodes.

    Doh, I wish I had been well enough to continue my biochem degree into an offered PhD. It was on nematodes if I recall correctly, though more about pesticide resistance.
     
    FMMM1, Mel9 and pamojja like this.
  11. FMMM1

    FMMM1 Senior Member

    Messages:
    174
    Likes:
    283
    Thank you very much for your response. It's good to have your contributions since you have such a good understanding of biochemistry.

    Degrees not finished --- it seems the way in this disease.
     

See more popular forum discussions.

Share This Page