Shared genetic etiology and causality between COVID-19 and venous thromboembolism: evidence from genome-wide cross trait analysis and bi-directional Mendelian randomization study

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Abstract

Venous thromboembolism (VTE) occurs in up to one third patients with COVID-19. VTE and COVID-19 may share a common genetic architecture, which has not been clarified yet. To fill this gap, we leveraged summary-level genetic data from the latest COVID-19 host genetics consortium and UK Biobank and examined the shared genetic etiology and causal relationship between COVID-19 and VTE. The cross-trait analysis identified 8, 11, and 7 shared loci between VTE and severe COVID-19, COVID-19 hospitalization, SARS-CoV-2 infection respectively, in 13 genes involved in coagulation and immune function and enriched in the lung. Co-localization analysis identified eight shared loci in ABO, ADAMTS13 and FUT2 genes. Bi-direction Mendelian randomization suggested that VTE was associated with higher risks of all COVID-19 related traits, and SARS-CoV-2 infection was associated with higher risk of VTE. Our study provided timely evidence and novel insights into the genetic etiology between COVID-19 and VTE.

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  1. SciScore for 10.1101/2022.05.21.22275413: (What is this?)

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

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    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: We detected the following sentences addressing limitations in the study:
    We also acknowledge several limitations of our study. First, the GWAS data for COVID-19 and VTE used in this study were derived from the European population, so the associations may not be applicable to other ancestries. Second, although GWAS summary statistics conducted study-specific quality control, misclassification of COVID-19 might exist. Third, the summary statistics limit us to assess sex and age-specific genetic effects. Fourth, the GWAS of COVID-19 related traits might be conducted at different time periods, so there might be differences in the SARS-COV-2 infection strain. However, our study does not aim to assess the association with specific strain of SARS-COV-2 infection. Finally, although our study provides evidence of genetic correlation and genetic overlap between COVID-19 and VTE, the underlying biological mechanisms are still unclear, and further studies are still needed for validation. In conclusion, our findings provided novel evidence of genetic correlations between severe COVID-19, COVID-19 hospitalization, SARS-CoV-2 infection and VTE, and highlighted their common genetic architecture, with shared genes closely related to coagulation and immunity. Our works contribute to the understanding of COVID-19 and VTE etiology, and open up new insights into the prevention and comorbidity management of COVID-19.

    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.

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


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