Differential methylation as a mediator of COVID-19 susceptibility

  1. Sandra Steyaert
  2. Geert Trooskens
  3. Joris R. Delanghe
  4. Wim Van Criekinge

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Abstract

The COVID-19 outbreak shows a huge variation in prevalence and mortality on geographical level but also within populations 1 . The ACE2 gene, identified as the SARS-CoV2 receptor, has been shown to facilitate the viral invasion and people with higher ACE2 expression generally are more severely affected 2, 3 . As there is a lot of variability in ACE2 expression between individuals we hypothesized that differential DNA methylation profiles could be (one of) the confounding factors explaining this variability. Here we show that epigenetic profiling of host tissue, especially in the ACE2 promoter region and its homologue ACE1 , may be important risk factors for COVID-19. Our results propose that variable methylation can explain (part of) the differential susceptibility, symptom severity and death rate for COVID-19. Our findings are a promising starting point to further evaluate the potential of ACE1/2 methylation and other candidates as a predictor for clinical outcome upon SARS-CoV2 infection.

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  1. ScreenIT

    SciScore for 10.1101/2020.08.14.251538: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Methylation was measured on Illumina’s 450K methylation array for which raw data was downloaded from the Gene Expression Omnibus (GEO)23 (GSE30870, GSE32149, GSE36064, GSE41169, GSE42861).
    Gene Expression Omnibus
    suggested: (Gene Expression Omnibus (GEO, RRID:SCR_005012)
    Raw β-values were preprocessed in R (v3.6.3) with the RnBeads package (v2.4.0)25.
    RnBeads
    suggested: (RnBeads, RRID:SCR_010958)

    Results from OddPub: Thank you for sharing your data.

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • No funding statement was detected.
    • No protocol registration statement was detected.

    About SciScore

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  2. Version published to 10.1101/2020.08.14.251538v1 on bioRxiv