Passive Smoking and Thyroid Diseases: Association by Mendelian Randomization Study

Existing literature has primarily focused on the associations between active smoking and thyroid diseases, whereas the potential causal relationship between passive smoking and thyroid diseases remains insufficiently investigated. Therefore, we conducted a Mendelian randomization (MR) study to evaluate the potential associations of passive smoke exposure with seven prevalent thyroid diseases.

A two-sample MR design was employed using data from the IEU OpenGWAS Project. Five MR methods were applied to assess potential causal associations. Cochran's Q test assessed heterogeneity, MR-Egger regression evaluated horizontal pleiotropy, MR-PRESSO was used to detect global pleiotropy, and leave-one-out analyses tested result robustness.

Genetically predicted passive smoking was associated with increased risks of 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 the primary inverse variance weighting analysis, while showing an inverse 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.

This study provides suggestive evidence that genetically predicted passive smoking may be associated with increased risks of Graves' disease and thyroid cancer, as well as an inverse association with nontoxic single thyroid nodules. These findings support efforts to minimize exposure to tobacco smoke among passive smokers. The inverse association with nontoxic single thyroid nodules should be interpreted cautiously and warrants further investigation. Further studies using larger and more granular datasets are required to clarify the potential causal relationships between passive smoking and thyroid diseases.