TY - JOUR TI - 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 A2 - Janus, Edward D A2 - Serwadda, David M A2 - Janus, Edward D A2 - Jiang, Xia VL - 10 PY - 2021 DA - 2021/12/06 SP - e73873 C1 - eLife 2021;10:e73873 DO - 10.7554/eLife.73873 UR - https://doi.org/10.7554/eLife.73873 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 two-sample Mendelian randomization (MR) study. Methods:. We used two kinds of genetic instruments to proxy the exposure of lipid-lowering drugs, including expression quantitative trait loci of drugs target genes, and genetic variants within or nearby drugs target genes associated with low-density lipoprotein (LDL cholesterol from genome-wide association study). 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 (odds ratio [OR] = 1.38, 95% confidence interval [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 two-sample MR study suggested a potential causal relationship between HMGCR inhibition and the reduced risk of COVID-19 hospitalization. Funding:. Start-up Fund for high-level talents of Fujian Medical University. KW - lipid-lowering drugs KW - COVID-19 KW - mendelian randomization JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -