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

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

doi:10.3389/fphar.2023.1171404

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

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

Authors

Hongfei Song¹, Na Lei¹, Ling Zeng¹, Xiuyan Li¹, Cen Jiang¹, Quansheng Feng¹, Yue Su¹, Jibin Liu¹, Jie Mu¹

Affiliation

¹ Traditional Chinese Medicine and Inflammation Regulation Research Group, School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

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.

Grants and funding

This work was supported by the National Interdisciplinary Innovation Group of Traditional Chinese Medicine—“Innovative Team for Clinical Efficacy Evaluation and Mechanism Research of Traditional Chinese Medicine for COVID-19” (ZYYCXTD-D-202201).