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Thread: Genomewide Association Study of Severe Covid-19 with Respiratory Failure

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    Genomewide Association Study of Severe Covid-19 with Respiratory Failure

    From new England Journal of Medicine
    https://www.nejm.org/doi/full/10.1056/NEJMoa2020283

    Genomewide Association Study of Severe
    Covid-19 with Respiratory Failure

    BACKGROUND
    There is considerable variation in disease behavior among patients infected with
    severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that
    causes coronavirus disease 2019 (Covid-19). Genomewide association analysis may
    allow for the identification of potential genetic factors involved in the development
    of Covid-19.
    METHODS
    We conducted a genomewide association study involving 1980 patients with Covid-19
    and severe disease (defined as respiratory failure) at seven hospitals in the Italian
    and Spanish epicenters of the SARS-CoV-2 pandemic in Europe. After quality control
    and the exclusion of population outliers, 835 patients and 1255 control participants
    from Italy and 775 patients and 950 control participants from Spain were
    included in the final analysis. In total, we analyzed 8,582,968 single-nucleotide
    polymorphisms and conducted a meta-analysis of the two case–control panels.
    RESULTS
    We detected cross-replicating associations with rs11385942 at locus 3p21.31 and
    with rs657152 at locus 9q34.2, which were significant at the genomewide level
    (P<5×10−8) in the meta-analysis of the two case–control panels (odds ratio, 1.77;
    95% confidence interval [CI], 1.48 to 2.11; P = 1.15×10−10; and odds ratio, 1.32; 95%
    CI, 1.20 to 1.47; P = 4.95×10−8, respectively). At locus 3p21.31, the association signal
    spanned the genes SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6 and XCR1. The association
    signal at locus 9q34.2 coincided with the ABO blood group locus; in this cohort, a
    blood-group–specific analysis showed a higher risk in blood group A than in other
    blood groups (odds ratio, 1.45; 95% CI, 1.20 to 1.75; P = 1.48×10−4) and a protective
    effect in blood group O as compared with other blood groups (odds ratio, 0.65;
    95% CI, 0.53 to 0.79; P = 1.06×10−5).
    CONCLUSIONS
    We identified a 3p21.31 gene cluster as a genetic susceptibility locus in patients
    with Covid-19 with respiratory failure and confirmed a potential involvement of the
    ABO blood-group system. (Funded by Stein Erik Hagen and others.)

    Following that Svante Paabo found that this location came from Neanderthals

    https://www.biorxiv.org/content/10.1...07.03.186296v1

    https://medium.com/@johnhawks/neande...e-c258dc8bc2c9 a discussion about the significance of the result.
    Image “Westray wifie” replica of Neolithic figurine Hidden Content
    Out of 64 pre 1800 births 45% Cheshire, 1% Irish (or Scottish), 25% south Derbyshire, 13% Burton on Trent area (where 4 counties within 10 miles), 7% Shropshire, 1% Staffs, 8% Lancs. So far all British Isles despite what some testing companies say.

  2. The Following 4 Users Say Thank You to Judith For This Useful Post:

     BalkanKiwi (07-08-2020),  DMXX (07-08-2020),  JonikW (07-08-2020),  Táltos (07-08-2020)

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    Thank you - This paper was discussed within a different COVID thread briefly:

    https://anthrogenica.com/showthread....otective/page6

    This is the first published GWAS we have for COVID - Unfortunate that only one SNP achieved significance. Potentially because the cohort size was underpowered.

  4. The Following 5 Users Say Thank You to DMXX For This Useful Post:

     BalkanKiwi (07-08-2020),  JonikW (07-08-2020),  Judith (07-09-2020),  pmokeefe (07-22-2020),  Táltos (07-08-2020)

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