Multi-ancestry fine mapping implicates OAS1 splicing in risk of severe COVID-19

  1. Jennifer E. Huffman
  2. Guillaume Butler-Laporte
  3. Atlas Khan
  4. Erola Pairo-Castineira
  5. Theodore G. Drivas
  6. Gina M. Peloso
  7. Tomoko Nakanishi
  8. COVID-19 Host Genetics Initiative
  9. Andrea Ganna
  10. Anurag Verma
  11. J. Kenneth Baillie
  12. Krzysztof Kiryluk
  13. J. Brent Richards
  14. Hugo Zeberg

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Abstract

The OAS1/2/3 cluster has been identified as a risk locus for severe COVID-19 among individuals of European ancestry, with a protective haplotype of approximately 75 kilobases (kb) derived from Neanderthals in the chromosomal region 12q24.13. This haplotype contains a splice variant of OAS1 , which occurs in people of African ancestry independently of gene flow from Neanderthals. Using trans-ancestry fine-mapping approaches in 20,779 hospitalized cases, we demonstrate that this splice variant is likely to be the SNP responsible for the association at this locus, thus strongly implicating OAS1 as an effector gene influencing COVID-19 severity.

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  1. Version published to 10.1038/s41588-021-00996-8
  2. Version published to 10.1101/2021.03.20.21254005v2 on medRxiv
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    SciScore for 10.1101/2021.03.20.21254005: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: All participants gave appropriate consent and ethical approvals were obtained from the relevant research ethics boards
    IRB: Summary statistics - Biobanque Québécoise de la COVID-19: The Biobanque Québécoise de la COVID-19 (BQC-19) is a prospective hospital-based biobank recruiting patients with proven or suspected COVID-19 (Jewish General Hospital research ethics board no. 2020-2137).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableThe mean age of cases was 62.89 years, and the percentage of females was 43%.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    MEGA) chip.
    MEGA
    suggested: (Mega BLAST, RRID:SCR_011920)
    e disequilibrium: Linkage disequilibrium was calculated using LDlink19 4.1 in the genomic region 113.30-113.45 Mb (hg19) using data from the 1000 Genomes Project10.
    1000 Genomes Project10
    suggested: None

    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.

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  4. Version published to 10.1101/2021.03.20.21254005v1 on medRxiv