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Integration of DNA methylation & health scores identifies subtypes in MECFS

Discussion in 'Latest ME/CFS Research' started by Murph, Apr 26, 2018.

  1. Murph

    Murph :)

    Integration of DNA methylation & health scores identifies subtypes in myalgic encephalomyelitis/chronic fatigue syndrome.
    de Vega WC1,2,Erdman L3,4,Vernon SD5,Goldenberg A3,4,McGowan PO1,2,6,7.
    Author information

    To identify subtypes in myalgic encephalomyelitis/chronic fatigue syndrome(ME/CFS) based on DNA methylation profiles and health scores.

    DNA methylome profiles in immune cells were integrated with symptomatology from 70 women with ME/CFS using similarity network fusion to identify subtypes.

    We discovered four ME/CFS subtypes associated with DNA methylation modifications in 1939 CpG sites, three RAND-36 categories and five DePaul Symptom Questionnaire measures. Methylation patterns of immune response genes and differences in physical functioning and postexertional malaise differentiated the subtypes.

    ME/CFS subtypes are associated with specific DNA methylation differences and health symptomatology and provide additional evidence of the potential relevance of metabolic and immune differences in ME/CFS with respect to specific symptoms.

    CFS; DNA methylation;chronic fatigue syndrome; clinical subtyping; complex disease; epigenetics; health survey; myalgic encephalomyelitis; similarity network fusion; symptom heterogeneity

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  2. Murph

    Murph :)

    This study is a real slow burner. They find four subgroups. I didn't get it at all at first but now it seems very good - they are finding that certain genetic issues match onto those four symptom subgroups.

    Where I got excited is when I discovered the genes in question are mostly to do with metabolism and immunity:

    Methylation differences at 1939 sites of the 4699 ME/CFS potential biomarker sites were identified to significantly differentiate the four subtypes (Supplementary Table 3). Interestingly, three of the top five sites (Figure 4 & Table 4) were associated with genes involved in endoplasmic reticulum and mitochondrial processes (TECR, GPD2, PACS2), and the majority of the top five differentially methylated sites in each subtype contained genes that were related to oxidative respiration (COX10, which had decreased methylation in subtype 1 and an increase in methylation in subtype 4) and cellular transcription regulation (KLF6 in subtype 2, and MLLT1 which had decreased methylation in subtype 1 and increased methylation in subtype 3) (Table 6).

    These findings support previous work implicating cellular energy and metabolic dysfunction in ME/CFS [16,55]. Subtypes 1 and 4, the more debilitated subtypes according to clinical scores, appear to have distinct epigenetic signatures relating to metabolic genes, while subtypes 2 and 3 primarily exhibit changes in genes that regulate transcription.

    When we investigated the potential functional classes of genes associated with the top 50 sites that contributed to patient clustering, we found that these genes were predominantly related to immune signaling, especially in T-cell responses (Table 5 & Supplementary Table 5). One of the top five differentially methylated sites in subtype 3 was found in IL12RB1, which encodes for the IL-12 receptor, which shifts immune response from a Th1- to a Th2- mediated response[56]. These findings align with our previous study [14] and others that have described heterogeneity in functional and proportion differences in T cells of ME/CFS patients [57,58].

    Overall, our results suggest that methylation differences in genes related to metabolic and immune responses are associated with physical functioning and postexertional malaise in ME/CFS subtypes (Tables 2 & 3). It is possible that differential methylation at these genes may lead to impairments in metabolic processes and immune signaling, which would result in decreased physical functioning and increased incidence of postexertional malaise.
    sb4, FMMM1, Simon and 3 others like this.
  3. FMMM1

    FMMM1 Senior Member

    Thanks for this.

    Check these articles out:

    Ron Davis/Mike Synder are just starting to work on an NIH funded project looking at HLA genes in ME/CFS. Interesting to see if they find halotypes(?) which predispose/protect. Also, evidence of methylation/demethylation i.e. epigenetic changes in ME/CFS.

    Note interest by MS researchers (above articles); which may help to move things on i.e. in ME/CFS.

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