Passive Smoking and Thyroid Diseases: Association by Mendelian Randomization Study

INTRODUCTION: Existing literature has primarily focused on the associations between active smoking and thyroid diseases, while the causal mechanisms linking passive smoking to thyroid diseases remain insufficiently investigated. Therefore, we conducted a Mendelian randomization (MR) study to evaluate the potential causal effects of passive smoke exposure on seven prevalent thyroid diseases. METHODS: A two-sample MR design was employed using data from the IEU Open GWAS Project. Five MR methods were applied to evaluate causality. Cochran's Q test assessed heterogeneity, MR-Egger regression evaluated horizontal pleiotropy, and leave-one-out analyses tested result robustness. RESULTS: Passive smoking was identified as a risk factor for Graves' disease (odds ratio [OR] = 1.873; 95% confidence interval [CI]: 1.011-3.470; P = 0.046) and thyroid cancer (OR = 1.515; 95% CI: 1.080-2.125; P = 0.016) in our study, while showing a protective association with nontoxic single thyroid nodules (OR = 0.670; 95% CI: 0.480-0.935; P = 0.019). No causal associations were observed with hyperthyroidism/thyrotoxicosis, hypothyroidism, autoimmune thyroiditis, or subacute thyroiditis. CONCLUSION: This study demonstrated a positive association between passive smoking and the risks of Graves' disease and thyroid cancer, as well as a negative association with nontoxic single thyroid nodules. However, no causal relationships were observed with other thyroid diseases. These findings suggested that minimizing exposure to tobacco smoke among passive smokers might reduce the risk of certain associated thyroid diseases. The protective effect of passive smoking on nontoxic single thyroid nodules should be interpreted cautiously and warrants further investigation. Additionally, more studies with multiple approaches are warranted to further investigate the potential causal relationships between the intensity of passive smoking and other thyroid diseases.