No genetic causal association between systemic lupus erythematosus and COVID-19

Shu-Zhen Xu; Zhi-Xin Wang; Xi Fang; Cong Chen; Xiao-Ke Yang; Zong-Wen Shuai; Sha-Sha Tao

doi:10.3389/fimmu.2023.1183570

No genetic causal association between systemic lupus erythematosus and COVID-19

Front Immunol. 2023 May 18:14:1183570. doi: 10.3389/fimmu.2023.1183570. eCollection 2023.

Authors

Shu-Zhen Xu^{1

2}, Zhi-Xin Wang³, Xi Fang^{1

2}, Cong Chen^{1

2}, Xiao-Ke Yang³, Zong-Wen Shuai³, Sha-Sha Tao^{1

2

4}

Affiliations

¹ Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China.
² Institute of Kidney Disease, Inflammation and Immunity Mediated Diseases, The Second Hospital of Anhui Medical University, Hefei, Anhui, China.
³ Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
⁴ Experimental Teaching Center for Preventive Medicine, School of Public Health, Anhui Medical University, Hefei, Anhui, China.

Abstract

Objective: Emerging evidence suggests an increased prevalence of coronavirus disease 2019 (COVID-19) in patients with systemic lupus erythematosus (SLE), the prototype of autoimmune disease, compared to the general population. However, the conclusions were inconsistent, and the causal relationship between COVID-19 and SLE remains unknown.

Methods: In this study, we aimed to evaluate the bidirectional causal relationship between COVID-19 and SLE using bidirectional Mendelian randomization (MR) analysis, including MR-Egger, weighted median, weighted mode, and the inverse variance weighting (IVW) method.

Results: The results of IVW showed a negative effect of SLE on severe COVID-19 (OR = 0.962, p = 0.040) and COVID-19 infection (OR = 0.988, p = 0.025), which disappeared after Bonferroni correction. No causal effect of SLE on hospitalized COVID-19 was observed (OR = 0.983, p = 0.148). In the reverse analysis, no causal effects of severe COVID-19 infection (OR = 1.045, p = 0.664), hospitalized COVID-19 (OR = 0.872, p = 0.109), and COVID-19 infection (OR = 0.943, p = 0.811) on SLE were found.

Conclusion: The findings of our bidirectional causal inference analysis did not support a genetically predicted causal relationship between SLE and COVID-19; thus, their association observed in previous observational studies may have been caused by confounding factors.

Keywords: COVID-19; Mendelian randomization; causal relationship; genetic association; systemic lupus erythematosus.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Autoimmune Diseases*
COVID-19* / complications
Causality
Humans
Lupus Erythematosus, Systemic* / complications
Lupus Erythematosus, Systemic* / epidemiology
Lupus Erythematosus, Systemic* / genetics
Mendelian Randomization Analysis

Grants and funding

This study was funded by grants from the National Natural Science Foundation of China (81872687) and the University Natural Science Research Project of Anhui Province (KJ2021A0230) and Postgraduate InnovationResearch and Practice Program of Anhui Medical University (YJS20230007).