Inheritance of a common androgen synthesis variant allele is associated with female COVID susceptibility in UK Biobank
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Abstract
Context
A sex discordance in COVID exists, with males disproportionately affected. Although sex steroids may play a role in this discordance, no definitive genetic data exist to support androgen-mediated immune suppression neither for viral susceptibility nor for adrenally produced androgens.
Objective
The common adrenal-permissive missense-encoding variant HSD3B1(1245C) that enables androgen synthesis from adrenal precursors and that has been linked to suppression of inflammation in severe asthma was investigated in COVID susceptibility and outcomes reported in the UK Biobank.
Methods
The UK Biobank is a long-term study with detailed medical information and health outcomes for over 500 000 genotyped individuals. We obtained COVID test results, inpatient hospital records, and death records and tested for associations between COVID susceptibility or outcomes and HSD3B1(1245A/C) genotype. Primary analyses were performed on the UK Biobank Caucasian cohort. The outcomes were identification as a COVID case among all subjects, COVID positivity among COVID-tested subjects, and mortality among subjects identified as COVID cases.
Results
Adrenal-permissive HSD3B1(1245C) genotype was associated with identification as a COVID case (odds ratio (OR): 1.11 per C allele, 95% CI: 1.04–1.18, P = 0.0013) and COVID-test positivity (OR: 1.09, 95% CI: 1.02–1.17, P = 0.011) in older (≥70 years of age) women. In women identified as COVID cases, there was a positive linear relationship between age and 1245C allele frequency (P < 0.0001). No associations were found between genotype and mortality or between genotype and circulating sex hormone levels.
Conclusion
Our study suggests that a common androgen synthesis variant regulates immune susceptibility to COVID infection in women, with increasingly strong effects as women age.
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SciScore for 10.1101/2020.08.27.20183004: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: This study was approved by the NHS National Research Ethics Committee (REC ref 16/NW/0274) through the generic ethical approval for UK Biobank studies (approved UK Biobank application #44578). Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not 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 …SciScore for 10.1101/2020.08.27.20183004: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: This study was approved by the NHS National Research Ethics Committee (REC ref 16/NW/0274) through the generic ethical approval for UK Biobank studies (approved UK Biobank application #44578). Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not 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.
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