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. 2023 Jun 16:14:1171404.
doi: 10.3389/fphar.2023.1171404. eCollection 2023.

Mendelian randomization analysis identified tumor necrosis factor as being associated with severe COVID-19

Hongfei Song  1 , Na Lei  1 , Ling Zeng  1 , Xiuyan Li  1 , Cen Jiang  1 , Quansheng Feng  1 , Yue Su  1 , Jibin Liu  1 , Jie Mu  1
Affiliations

Mendelian randomization analysis identified tumor necrosis factor as being associated with severe COVID-19

Hongfei Song et al. Front Pharmacol. .

Abstract

Background: Observational studies have shown that anti-tumor necrosis factor (TNF) therapy may be beneficial for patients with coronavirus disease 2019 (COVID-19). Nevertheless, because of the methodological restrictions of traditional observational studies, it is a challenge to make causal inferences. This study involved a two-sample Mendelian randomization analysis to investigate the causal link between nine TNFs and COVID-19 severity using publicly released genome-wide association study summary statistics. Methods: Summary statistics for nine TNFs (21,758 cases) were obtained from a large-scale genome-wide association study. Correlation data between single-nucleotide polymorphisms and severe COVID-19 (18,152 cases vs. 1,145,546 controls) were collected from the COVID-19 host genetics initiative. The causal estimate was calculated by inverse variance-weighted (IVW), MR-Egger, and weighted median methods. Sensitivity tests were conducted to assess the validity of the causal relationship. Results: Genetically predicted TNF receptor superfamily member 6 (FAS) positively correlated with the severity of COVID-19 (IVW, odds ratio = 1.10, 95% confidence interval = 1.01-1.19, p = 0.026), whereas TNF receptor superfamily member 5 (CD40) was protective against severe COVID-19 (IVW, odds ratio = 0.92, 95% confidence interval = 0.87-0.97, p = 0.002). Conclusion: Genetic evidence from this study supports that the increased expression of FAS is associated with the risk of severe COVID-19 and that CD40 may have a potential protective effect against COVID-19.

Keywords: COVID-19; Mendelian randomization analyses; causal associations; genome-wide association study; tumor necrosis factor.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Summary of data sources and flowchart of the research design.
FIGURE 2
FIGURE 2
Correlation of TNF genetic predisposition with severe COVID-19.
FIGURE 3
FIGURE 3
Scatter plot of SNPs associated with CD40 levels (A) and FAS levels (B) and severe COVID-19 after outlier removal with MR-PRESSO. Analyses were performed through inverse variance-weighted, weighted median, and MR‒Egger methods. The slope of each line corresponds to the estimated MR effect per method.
See this image and copyright information in PMC

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