Background This study employed Mendelian randomization to investigate the relationships between pathogenic infections, immunophenotypes, and Hashimoto’s thyroiditis, providing deeper insights into infection-induced Hashimoto’s thyroiditis development beyond the limitations of small, inconclusive observational studies. Methods Data on pathogenic infections, immune cells, and Hashimoto’s thyroiditis were obtained from public databases. The inverse variance weighted method was used as the primary analytical approach, with robustness of the findings confirmed through heterogeneity and pleiotropy tests. Results Mendelian randomization analysis demonstrated a causal relationship between anti-polyomavirus 2 IgG seropositivity and Hashimoto’s thyroiditis (inverse variance weighted: odds ratio = 1.145, 95% confidence interval: 1.069–1.225, p = 9.90e−05). There was insufficient evidence to support a reverse causal relationship (inverse variance weighted: odds ratio = 1.092, 95% confidence interval: 0.892–1.337, p = 3.94e−01). The proportion of variation in genetically predicted anti-polyomavirus 2 IgG seropositivity mediated by CD20 + IgD + CD38 − B cells was 6.36% (95% confidence interval: 1.38%–11.35%). Conclusion Mendelian randomization analysis revealed that polyomavirus 2 infection significantly contributed to the development of Hashimoto’s thyroiditis, mediated by CD20 + IgD + CD38⁻ B cells. However, no causal associations were observed between Hashimoto’s thyroiditis and other commonly studied pathogens, including human herpesvirus 6, hepatitis C virus, Epstein–Barr virus, and Helicobacter pylori .
Zhou et al. (Thu,) studied this question.