ArticleJournal of medical virology2023
Does ACE2 mediate the detrimental effect of exposures related to COVID-19 risk: A Mendelian randomization investigation.
Article in Journal of medical virology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
8 citing papers in PubMed, 1 synthesis or guideline pooled it, 9 citations in OpenAlex.
- Micronutrients, Vitamin D, and Inflammatory Biomarkers in COVID-19: A Systematic Review and Meta-analysis of Causal Inference Studies.Nutrition reviews · 2025Pooled it
- Development and validation of a prediction model for adverse outcomes in viral pneumonia using CT-based quantitative body composition analysis.Journal of thoracic disease · 2026Article
- Potential relationships between circulating gene expression ofJournal of Zhejiang University. Science. B · 2025Article
- Causal association and shared genetics between telomere length and COVID-19 outcomes: New evidence from the latest large-scale summary statistics.Computational and structural biotechnology journal · 2024Article
- Diabetes Mellitus, Energy Metabolism, and COVID-19.Endocrine reviews · 2024Review
- Actionable targets to reduce COVID-19 severity.Nature metabolism · 2023Article
- Does ACE2 mediate the detrimental effect of exposures related to COVID-19 risk: A Mendelian randomization investigation.Journal of medical virology · 2023Article
- Mendelian randomization analysis identified tumor necrosis factor as being associated with severe COVID-19.Frontiers in pharmacology · 2023Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesAdiposity, smoking, and lower socioeconomic position (SEP) increase COVID-19 risk while the association of vitamin D, blood pressure, and glycemic traits in COVID-19 risk were less clear. Whether angiotensin-converting enzyme 2 (ACE2), the key receptor for SARS-CoV-2, mediates these associations has not been investigated. We conducted a Mendelian randomization study to assess the role of these exposures in COVID-19 and mediation by ACE2.
methodsWe extracted genetic variants strongly related to various exposures (vitamin D, blood pressure, glycemic traits, smoking, adiposity, and educational attainment [SEP proxy]), and ACE2 cis-variants from genome-wide association studies (GWAS, n ranged from 28 204 to 3 037 499) and applied them to GWAS summary statistics of ACE2 (n = 28 204) and COVID-19 (severe, hospitalized, and susceptibility, n ≤ 2 942 817). We used inverse variance weighted as the main analyses, with MR-Egger and weighted median as sensitivity analyses. Mediation analyses were performed based on product of coefficient method.
resultsHigher adiposity, lifetime smoking index, and lower educational attainment were consistently associated with higher risk of COVID-19 phenotypes while there was no strong evidence for an association of other exposures in COVID-19 risk. ACE2 partially mediates the detrimental effects of body mass index (ranged from 4.3% to 8.2%), waist-to-hip ratio (ranged from 11.2% to 16.8%), and lower educational attainment (ranged from 4.0% to 7.5%) in COVID-19 phenotypes while ACE2 did not mediate the detrimental effect of smoking.
conclusionsWe provided genetic evidence that reducing ACE2 could partly lower COVID-19 risk amongst people who were overweight/obese or of lower SEP.
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