Association of lipid-lowering drugs with COVID-19 outcomes from a Mendelian randomization study

  1. Wuqing Huang
  2. Jun Xiao
  3. Jianguang Ji  Is a corresponding author
  4. Liangwan Chen  Is a corresponding author
  1. Fujian Medical University, China
  2. Fujian Medical University Union Hospital, China
  3. 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.

The following previously published data sets were used

Article and author information

Author details

  1. Wuqing Huang

    Department of Epidemiology and Health Statistics, Fujian Medical University, Fuzhou, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7616-8622
  2. Jun Xiao

    Department of Cardiovascular Surgery, Fujian Medical University Union Hospital, Fuzhou, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5046-5493
  3. Jianguang Ji

    Center for Primary Health Care Research, Department of Clinical Sciences, Lund University, Malmö, Sweden
    For correspondence
    jianguang.ji@med.lu.se
    Competing interests
    The authors declare that no competing interests exist.
  4. Liangwan Chen

    Department of Cardiovascular Surgery, Fujian Medical University Union Hospital, Fuzhou, China
    For correspondence
    chenliangwan@fjmu.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4211-3842

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.

Reviewing Editor

  1. Edward D Janus, University of Melbourne, Australia

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.

Version history

  1. Preprint posted: July 24, 2021 (view preprint)
  2. Received: September 14, 2021
  3. Accepted: November 22, 2021
  4. Accepted Manuscript published: December 6, 2021 (version 1)
  5. Version of Record published: December 24, 2021 (version 2)

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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  1. Wuqing Huang
  2. Jun Xiao
  3. Jianguang Ji
  4. Liangwan Chen
(2021)
Association of lipid-lowering drugs with COVID-19 outcomes from a Mendelian randomization study
eLife 10:e73873.
https://doi.org/10.7554/eLife.73873

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https://doi.org/10.7554/eLife.73873

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