Association of lipid-lowering drugs with COVID-19 outcomes from a Mendelian randomization study
- Fujian Medical University, China
- Fujian Medical University Union Hospital, China
- Lund University, Sweden
Abstract
Background: Lipid metabolism plays an important role in viral infections. We aimed to assess the causal effect of lipid-lowering drugs (HMGCR inhibitiors, PCSK9 inhibitiors and NPC1L1 inhibitior) on COVID-19 outcomes using 2-sample Mendelian Randomization (MR) study.
Methods: We used two kinds of genetic instruments to proxy the exposure of lipid-lowering drugs, including eQTLs of drugs target genes, and genetic variants within or nearby drugs target genes associated with LDL cholesterol from GWAS. Summary-data-based MR (SMR) and inverse-variance weighted MR (IVW-MR) were used to calculate the effect estimates.
Results: SMR analysis found that a higher expression of HMGCR was associated with a higher risk of COVID-19 hospitalization (OR=1.38, 95%CI=1.06-1.81). Similarly, IVW-MR analysis observed a positive association between HMGCR-mediated LDL cholesterol and COVID-19 hospitalization (OR=1.32, 95%CI=1.00-1.74). No consistent evidence from both analyses was found for other associations.
Conclusions: This 2-sample MR study suggested a potential causal relationship between HMGCR inhibition and the reduced risk of COVID-19 hospitalization.
Funding: Fujian Province Major Science and Technology Program.
Data availability
Individual-level data cannot be provided but the raw data of the eQTLGen Consortium, GTEx and COVID-19 Host Genetics Initiative can be acessed at https://www.eqtlgen.org/, https://gtexportal.org/, and https://www.covid19hg.org/ , respectively. Summary-level GWAS or eQTL data and code used to produce main results have been uploaded to GitHub(https://github.com/WH57/lipid_covid19.git). All MR results and GWAS or eQTL associations of selected SNPs were provided in theSupplementary File 1 - Tables 2 to 4.
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Author details
Funding
Fujian Province Major Science and Technology Program (2018YZ001-1)
- Liangwan Chen
The funder had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: This 2-sample MR study is based on publicly available summary-level data from genome-wide association studies (GWASs) and expression quantitative trait loci (eQTLs) studies. All these studies had been approved by the relevant institutional review boards and participants had provided informed consents.
Copyright
© 2021, Huang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Association of lipid-lowering drugs with COVID-19 outcomes from a Mendelian randomization study
eLife 10:e73873.
https://doi.org/10.7554/eLife.73873
