| Title: | Sex-specific causal effects of serum sex hormones on COVID-19 susceptibility and severity: Evidence from the UK Biobank and COVID-19 Host Genetics Initiative |
| Journal: | Computational and Structural Biotechnology Reports |
| Published: | 1 Dec 2024 |
| DOI: | https://doi.org/10.1016/j.csbr.2024.100016 |
Publication 13938
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Abstract
Background Several hormone therapies, such as androgen receptor signaling inhibition, are being investigated for their potential effectiveness against coronavirus disease 2019 (COVID-19). However, the causal relationships between serum sex hormones and the predisposition to, as well as the severity of, COVID-19, with a particular emphasis on potential gender-specific impacts, remain elusive. Methods In this study, using the latest data from the UK Biobank (up to 424,907 individuals) and COVID-19 Host Genetics Initiative (up to 1,878,143 individuals), we conducted a two-sample Mendelian randomization (MR) to systematically assess the sex-specific causal effects of serum sex hormone levels, total testosterone (TT), bioavailable testosterone (BT) in particular, on COVID-19 outcomes. The inverse-variance weighted method was used in the main MR analysis. Furthermore, we additionally performed a series of sensitivity analyses to assess the robustness of MR effect estimates against potential biases caused by invalid genetic variants. Results Our MR analysis revealed novel causal associations between bioavailable testosterone and serum estradiol levels, and SARS-CoV-2 infection in women, but not men, except for a suggestive inverse causal association between estradiol levels and COVID-19 severity in men. Conclusion These novel findings improve our understanding of the sex-specific causal nature of androgen and estrogen in relation to COVID-19 outcomes, and suggest that bioavailable testosterone and estradiol levels may serve as potential therapeutic targets for preventing SARS-CoV-2 infection and improving patient outcomes.</p>
6 Authors
- Jian Zhao
- Huiqing Pan
- Shuyan Jin
- Dong Liu
- Xue Gao
- Fei Li
Enabling scientific discoveries that improve human health