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

Wuqing Huang; Jun Xiao; Jianguang Ji; Liangwan Chen

doi:10.7554/eLife.73873

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

Wuqing Huang, Jun Xiao, Jianguang Ji, Liangwan Chen

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	e73873
Journal	eLife
Volume	10
Early online date	2021
DOIs	https://doi.org/10.7554/eLife.73873
Publication status	Published - 2021

Subject classification (UKÄ)

Cardiac and Cardiovascular Systems
Medical Genetics

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10.7554/eLife.73873Licence: CC BY

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title = "Association of lipid-lowering drugs with COVID-19 outcomes from a Mendelian randomization study",

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.",

author = "Wuqing Huang and Jun Xiao and Jianguang Ji and Liangwan Chen",

note = "{\textcopyright} 2021, Huang et al.",

year = "2021",

doi = "10.7554/eLife.73873",

language = "English",

volume = "10",

journal = "eLife",

issn = "2050-084X",

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T1 - Association of lipid-lowering drugs with COVID-19 outcomes from a Mendelian randomization study

AU - Huang, Wuqing

AU - Xiao, Jun

AU - Ji, Jianguang

AU - Chen, Liangwan

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

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DO - 10.7554/eLife.73873

M3 - Article

C2 - 34866576

SN - 2050-084X

VL - 10

JO - eLife

JF - eLife

M1 - e73873

ER -

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

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