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Genome-epigenome interactions associated with ME/CFS, 2018, McGowan et al.

Discussion in 'BioMedical ME/CFS Research' started by Binkie4, Dec 6, 2018.

  1. Binkie4

    Binkie4 Senior Member (Voting Rights)

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  2. Trish

    Trish Moderator Staff Member

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    Abstract broken into short paragraphs for ease of reading.

     
  3. Lisa108

    Lisa108 Senior Member (Voting Rights)

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  4. ScottTriGuy

    ScottTriGuy Senior Member (Voting Rights)

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  5. ScottTriGuy

    ScottTriGuy Senior Member (Voting Rights)

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    For the ladies...

    "...
    The SNP that we found in signifi- cant association with ME/CFS in females, rs11712777
    ...
    rs11712777, and the genes in LD with it, form an expression quantitative trail loci (eQTL) alter- ing the expression of the CCK (cholecystokinin peptide hormone) gene. CCK has a number of active forms, expressed in a variety of tissues, including the intestine and blood [32], and plays a role in appetite, body weight and immune sys- tem function [32,33]. A rat knockout (KO) of the cholecystokinin B receptor (CCKBR) shows atte- nuated sickness behaviour [34]. This sickness behaviour in rats has remarkable similarity to some of the symptoms of ME/CFS [35], including fatigue, malaise, hyperalgesia, sleepiness, anhedo- nia, weight loss and diminished activity [35]. CCK is also co-localized with sleep-promoting preoptic neurons in the hypothalamus [36], which may relate to fatigue and unrefreshing sleep symptoms in ME/CFS. Finally, recent evi- dence suggests that CCK has a role regulating the differentiation of CD4+ T-cells [37], and that CCK-expressing neurons are a critical cellular component of the hypothalamic–pituitary–adre- nal axis [38]. These roles of CCK in components of the immune system are consistent with sug- gested immune dysregulation in ME/CFS
     
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  6. Hutan

    Hutan Moderator Staff Member

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    Regarding SNPS:
    Of the 2 million SNPS analysed, nothing was significant in the total sample population:
    When they just looked at females, they found one significant SNP:
    And even that finding wasn't very strong:
    And there was no result consistent with other genetic association studies (although no other studies had looked at rs11712777):
     
  7. Trish

    Trish Moderator Staff Member

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    It seems that there are now several different teams doing work on genetics and epigenetics in small groups of patients. I really hope they will put all the genome data together to do a bigger study. Surely that would be much more powerful than lots of little studies each finding small associations that might just be chance variation.
    The Alan Light talk this week looked at a bigger sample and focused on genes related to immunological and energy processes and found some potentially interesting associations.
    https://www.s4me.info/threads/lives...ations-create-susceptibility-for-me-cfs.7072/
     
  8. Michiel Tack

    Michiel Tack Senior Member (Voting Rights)

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    So these were 61 ME/CFS patients from the Bateman Horne Center whose blood samples were shipped to the University of Toronto. There they looked at (1) immune markers (2) genetic and (3) epigenetic variation in comparison to 48 healthy controls. Unfortunately the analyses seem to have yielded mostly null results.

    (1): "There were no differences between patients and controls in the relative proportions of CD19+ B-cells, CD14+ monocytes, CD3+ T-cells, CD4+/CD8- ‘helper’ T-cells or CD4-/CD8+ T-cells in PBMC lymphocyte samples."

    (2): "None of the more than 2 million variable SNP loci targeted in this study with the Human Omni 5–4 Array (Illumina Inc.) had a significant association (α = 0.05) with ME/CFS after p-value corrections."

    (3): "Of the 467,971 CpG loci targeted with the Human Methylation 450K Array (Illumina Inc.), 141 had significant associations with the ME/CFS phenotype (raw p-value < 0.05) [...] None of these differentially methylated loci were significant after FDR corrections. [...] These results are in contrast with previous findings by our group, which revealed thousands to tens of thousands of differentially methylated CpG loci associated with ME/CFS in PBMCs, using the same 450K array."

     
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  9. mariovitali

    mariovitali Senior Member (Voting Rights)

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    Please see this post for an association of NRG1 with Cholecystokinin (mentioned in the paper by McGowan et. al) , Vagus Nerve, Microglia activation (Dr. Jarred Younger), LXR and TAM Receptors :
     
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