Severe ME Day of Understanding and Remembrance: Aug. 8, 2017
Determined to paper the Internet with articles about ME, Jody Smith brings some additional focus to Severe Myalgic Encephalomyelitis Day of Understanding and Remembrance on Aug. 8, 2017 ...
Discuss the article on the Forums.

Pathway-focused genetic evaluation of immune and inflammation related genes with CFS

Discussion in 'Latest ME/CFS Research' started by Bob, Jun 28, 2015.

  1. Bob

    Bob

    Messages:
    9,846
    Likes:
    33,923
    England (south coast)
    This is a CDC study co-authored by Dr Unger, M Rajeevan and others. It follows on from Rajeevan's (CDC) recent paper on the same subject.

    (It came to my attention on Twitter via Linda Vansteenwinckel.)

    Open Access.

    Pathway-focused genetic evaluation of immune and inflammation related genes with chronic fatigue syndrome
    Mangalathu S. Rajeevan, , Irina Dimulescu, Janna Murray, Virginia R. Falkenberg, Elizabeth R. Unger
    Available online 24 June 2015
    Human Immunology
    doi:10.1016/j.humimm.2015.06.014
    http://www.sciencedirect.com/science/article/pii/S0198885915001809

     
    Last edited: Jun 28, 2015
    JaimeS, merylg, SOC and 5 others like this.
  2. Bob

    Bob

    Messages:
    9,846
    Likes:
    33,923
    England (south coast)
    Anyone who can read this entire paper, and report back on it, will get the Phoenix Rising special prize. (BTW, previously, the special prize was "The Bob" so please think carefully about whether you want one of these in your home!)

    I can't read this paper at the moment, so I skipped to the 'discussion' section, which starts as follows:
     
    merylg, SOC, jimells and 3 others like this.
  3. Dolphin

    Dolphin Senior Member

    Messages:
    10,557
    Likes:
    27,551
    Empiric criteria study unfortunately:

    The Reeves study found a prevalence of 2.54% of the population (i.e. very high. When they used the Fukuda criteria normally they got a prevalence of 0.235% to give you an idea of how many extra people the empiric criteria brings in).

    They see the empiric criteria (Reeves et al., 2005) as an operationalisation of the Fukuda criteria which is why they call it a Fukuda study (they do this on lots of their papers).
     
    SOC, Never Give Up, Simon and 2 others like this.
  4. Bob

    Bob

    Messages:
    9,846
    Likes:
    33,923
    England (south coast)
    Darn it, I thought the CDC had quietly abandoned the Reeves criteria.
     
    Last edited: Jun 28, 2015
    JaimeS, Never Give Up and Valentijn like this.
  5. Denise

    Denise Senior Member

    Messages:
    1,094
    Likes:
    3,435
    I wish they had abandoned it.
     
    SOC, ukxmrv, Never Give Up and 4 others like this.
  6. Dolphin

    Dolphin Senior Member

    Messages:
    10,557
    Likes:
    27,551
    They probably won't use it for the newer cohorts.. But this is on the Georgia sample.

    The study they published a couple of weeks ago http://forums.phoenixrising.me/inde...-from-pathway-focused-candidate-markers.38076 explicitly mentioned using the empiric criteria:

    That study also involved Mangalathu S. Rajeevan
     
  7. Valentijn

    Valentijn The Diabolic Logic

    Messages:
    14,075
    Likes:
    43,818
    It's a very good sign that most of the relevant SNPs listed are missense mutations or in the UTR regions. I haven't looked at the paper yet, but 23andMe does test for both the SNPs listed in the abstract: rs4151667 (minor allele "A", frequency 3%), and rs1061170 (minor allele "C", frequency 27%). Both the V3 and V4 chip test for those.
     
    merylg, SOC, ukxmrv and 3 others like this.
  8. Dolphin

    Dolphin Senior Member

    Messages:
    10,557
    Likes:
    27,551
    Note how they say:

    The MFI, SF-36 and SI are what they use for the empiric criteria.
     
  9. Valentijn

    Valentijn The Diabolic Logic

    Messages:
    14,075
    Likes:
    43,818
    For rs4151667 on the CFB gene, 4 out of 31 (12.9%) ME patients who I have data for are heterozygous ("AT"), compared to 1 out of 31 (3.2%) ethnically matched controls.

    For rs1061170 on the CFH gene, 14/54 (25.9%) alleles are "C", compared with 19/60 (31.7%) in ethnically matched controls. The ME patients have a lot of no-call results on that one.
     
    JaimeS, merylg and Never Give Up like this.
  10. nandixon

    nandixon Senior Member

    Messages:
    785
    Likes:
    1,893
    The Abstract gives a third SNP as well, rs11214105, located in the 5′ UTR of the IL18 gene. The minor allele for that SNP is "A" (frequency about 27-29% in European ethnicity populations).

    Assuming the minor allele is the risk allele for the 3 SNPs given, I'm homozygous negative for all three:

    rs4151667 TT -/-

    rs1061170 TT -/-

    rs11214105 GG -/-

    I'm probably in the majority subset of ME/CFS phenotypes, with PEM in the form of delayed severe post-exertional fatigue and additionally orthostatic intolerance that requires Florinef (and lots of other classic ME/CFS problems like IBS, etc.), and have had the disease for more than 17 years, so I'm a bit doubtful as to the study findings - relative to those particular SNPs, anyway. (Still have to read the full paper.)
     
    Last edited: Jun 28, 2015
    SOC and Bob like this.
  11. Bob

    Bob

    Messages:
    9,846
    Likes:
    33,923
    England (south coast)
    This paper is too complex for me to read and understand much of it at the moment, and too specialised for me to interpret it, but it does at least seem to suggest that the CDC are now taking ME/CFS seriously. The study used an unhelpful cohort, but that was probably for convenience, as they had already defined and identified the patients. They do seem to have retired the Reeves criteria now, when creating new cohorts.

    The paper includes detailed and specific discussions of the immune system all the way through it, and discusses (e.g.) specific genes, various types of immune cells, and cytokine polymorphisms in relation to specific symptoms in CFS.

    For example:
    In conclusion the paper says:
    So I would suggest that this is a sincere piece of work, doing a serious and sincere investigation into the biomedical pathogenesis of ME/CFS. As far as my limited understanding allows me to interpret it.
     
    Last edited: Jun 28, 2015
    A.B., JaimeS and Valentijn like this.
  12. medfeb

    medfeb Senior Member

    Messages:
    466
    Likes:
    1,838
    The problem with this study is that since it used the Empirical definition, its difficult to know what patient population the CDC is actually studying.

    As Dolphin points out, the Empirical definition increased prevalence 10-fold over earlier CDC estimates and 6-fold over Jason's estimate. The IOM noted that the empirical definition "resulted in a biased sample with overrepresentation of individuals with depression and posttraumatic stress disorder (PTSD)."

    Given that, I'd think its hard to say much about the relevance of these findings to ME.
     
    Valentijn, SOC and Bob like this.
  13. SOC

    SOC

    Messages:
    7,802
    Likes:
    16,454
    Agreed. They have found some interesting genetic correlations, but how specific they are to ME/CFS is unknown. The correlation may be more to chronic fatigue or neurochemical disturbance than to ME/CFS. That doesn't mean it isn't useful or show that there are abnormalities, just that the conclusion may not be specific to ME/CFS.

    If the Empiric collected nine non-ME chronic fatigue patients for every ME/CFS patient, it's also possible that the correlation applies more to non-ME conditions and that any actual genetic correlations to ME/CFS are lost in the noise.

    It will be interesting to see how any follow-up research using a better definition alters the results.
     
    medfeb, Bob, merylg and 1 other person like this.
  14. JaimeS

    JaimeS Senior Member

    Messages:
    3,112
    Likes:
    11,235
    Mid-Ohio Valley, United States
    Wow, @Bob, you are fast! I got wind of this in my email just now. :D
     
  15. JaimeS

    JaimeS Senior Member

    Messages:
    3,112
    Likes:
    11,235
    Mid-Ohio Valley, United States
    Umm:

    rs4151667 - TT
    rs1061170 - CT

    I don't appear to have data for rs11214105.

    ....but....but... darn it! ;)

    -J
     
    Valentijn likes this.
  16. Snow Leopard

    Snow Leopard Hibernating

    Messages:
    4,574
    Likes:
    12,123
    South Australia
    I'm not excited about this paper at all. It won't be replicated and it seems like the generation of a paper for the sake of it...
     
    Helen and Valentijn like this.
  17. Bob

    Bob

    Messages:
    9,846
    Likes:
    33,923
    England (south coast)
    I agree that it probably won't be replicated because of the infancy and complexity of the science and because of the cohort used. They need to be looking towards defining subsets, rather than comparing all-inclusive populations of fatigued patients with normal controls. But I'm not sure about your second point; Rajeevan seems to have a particular interest in this line of enquiry in ME/CFS, and the discussions in the paper are very detailed and specific. And I'd rather they were pursuing these lines of enquiry than an investigation of sleep patterns or the effects of employment on the quality of life of people with chronic fatigue. Not that I have enough expertise to really understand how robust or meaningful this study is. This science is very much in its infancy, so perhaps no point in getting excited by it yet.
     
    Last edited: Jun 30, 2015
    SOC and Valentijn like this.
  18. Snow Leopard

    Snow Leopard Hibernating

    Messages:
    4,574
    Likes:
    12,123
    South Australia
    It won't be replicated as the findings are not significant.
     
  19. Bob

    Bob

    Messages:
    9,846
    Likes:
    33,923
    England (south coast)
    Could you expanded on that at all? I haven't analysed the data.
     
    SOC likes this.
  20. Snow Leopard

    Snow Leopard Hibernating

    Messages:
    4,574
    Likes:
    12,123
    South Australia
    It's a limitation of these types of studies in general. Correction for multiple associations needs to be done not just for a few, but all possible, to eliminate bias. None of the P values for SNPs were <0.0000045

    In terms of meaningfullness of the results, unless there is a strong effect size, the results usually don't mean much.
     
    SOC and Valentijn like this.

See more popular forum discussions.

Share This Page