Genetically determined serum testosterone level and Covid-19 illness level: A mendelian randomization study

  1. Juan Xiong
  2. Xuejun Kong
  3. Ziyong Ma
  4. Yifei Qu
  5. Xu Yang
  6. Ruicheng Miao
  7. Jie Huang

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Abstract

Background

It is hypothesized that different levels of hormones especially serum testosterone level could explain the sex differences between men and women on the susceptibility and case fatality rate of COVID-19. However, traditional observational studies that support this hypothesis could not effectively establish the causal effects.

Objective

Utilizing recently published genome-wide associations studies (GWAS) on serum Testosterone level and on COVID-19 related phenotypes, we sought to assess the causality through Mendelian Randomization (MR) analyses. We further applied a suite of statistical genomics methods to further explore the biological mechanisms.

Results

We found that testosterone level is significantly associated with Covid-19 critical illness. All six MR methods yielded significant associations. There is no significant association between Testosterone and COVID-19 respiratory failure or COVID-19 susceptibility.

Conclusion

Based on the GWAS currently available, we provide support for a causal role of Testosterone on COVID-19 critical illness.Nevertheless, we recognize that the COVID-19 susceptibility GWAS effort is still ongoing and there is no such strong locus as CCR5 for HIV discovered for COVID-19.

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  1. ScreenIT

    SciScore for 10.1101/2021.10.10.21264779: (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:
    However, we realize the following limitations. First, the GWAS results on COVID-19 are inconsistent. The COVID-19 susceptibility GWAS effort is still ongoing and there is a lack of well-established loci. So, far, there is no such strong locus as CCR5 for HIV discovered for COVID-19. Although it is reasonable to hypothesize that the disease severity of COVID-19 has a strong genetic underpinning, the GWAS on these traits published so far are also inconsistent. The two GWAS used by the current study1011don’t have very consistent signals. Both studies only have thousands of cases, much smaller compared with many existing GWAS for other complex traits.

    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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  2. Version published to 10.1101/2021.10.10.21264779v1 on medRxiv