Adverse outcomes in SARS-CoV-2 infections are associated with a combination of variant genotypes at two loci in the APOL1 gene: a UK Biobank study

  1. Walt E Adamson
  2. Harry Noyes
  3. Anneli Cooper
  4. Georgia Beckett-Hill
  5. John Ogunsola
  6. Rulan Parekh
  7. Annette MacLeod

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Abstract

Risk of hospitalisation or death from COVID-19 in the UK is disproportionately high in people of African ancestry. Two APOL1 haplotypes (G1 and G2) found at high frequency only in populations of African descent are associated with increased risk of non-communicable and infectious diseases. Here, we test the hypothesis that adverse COVID-19 outcomes are also associated with these APOL1 high-risk variants. Within 9,433 individuals with African ancestry in the UK Biobank, there were 172 hospitalisations and 47 deaths attributed to COVID-19 as of December 2021. We examined APOL1 genotypes for association with hospitalisation and death while controlling for risk factors previously associated with poor COVID-19 outcomes. We identified an association between carriage of two APOL1 high-risk variants and death from COVID-19 (OR=2.7, 95% CI: 1.2-6.4). Stratified by genotype, those with G1/G2 had a higher odds of COVID-19 hospitalisation (OR=2.1, 95% CI: 1.1-3.8) and death (OR=5.9, 95% CI: 2.2-15.3) than G0/G0. There was no significant association detected in carriers of G1/G1 and G2/G2. These data suggest that the APOL1 G1/G2 genotype contributes to the increased rates of hospitalisation and mortality from COVID-19 in people of African ancestry, and could help to identify those at higher risk of severe COVID-19. This is especially relevant to geographical regions where APOL1 G1 and G2 high-risk variants are common, such as West and Central Africa and their diaspora.

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  1. Version published to 10.1101/2021.11.02.21265755v2 on medRxiv
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    SciScore for 10.1101/2021.11.02.21265755: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    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.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

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  3. Version published to 10.1101/2021.11.02.21265755v1 on medRxiv