Abstract
BACKGROUND: Graves disease (GD) is an autoimmune thyroid disorder characterized by hyperthyroidism and autoantibodies. The COVID-19 pandemic has raised questions about its potential relationship with autoimmune diseases like GD. OBJECTIVE: This study aims to investigate the causal association between COVID-19 and GD through Mendelian randomization (MR) analysis and assess the impact of COVID-19 on GD. METHODS: We conducted an MR study using extensive genome-wide association study data for GD and COVID-19 susceptibility and its severity. We used stringent single nucleotide polymorphism selection criteria and various MR methodologies, including inverse-variance weighting, MR-Egger, and weighted median analyses, to assess causal relationships. We also conducted tests for directional pleiotropy and heterogeneity, as well as sensitivity analyses. RESULTS: The MR analysis, based on the largest available dataset to date, did not provide evidence supporting a causal relationship between COVID-19 susceptibility (odds ratio [OR] 0.989, 95% CI 0.405-2.851; P=.93), COVID-19 hospitalization (OR 0.974, 95% CI 0.852-1.113; P=.70), COVID-19 severity (OR 0.979, 95% CI 0.890-1.077; P=.66), and GD. Tests for directional pleiotropy and heterogeneity, as well as sensitivity analyses, supported these findings. CONCLUSIONS: This comprehensive MR study does not provide sufficient evidence to support a causal relationship between COVID-19 and the onset or exacerbation of GD. These results contribute to a better understanding of the potential association between COVID-19 and autoimmune diseases, alleviating concerns about a surge in autoimmune thyroid diseases due to the pandemic. Further research is warranted to explore this complex relationship thoroughly.