Mediating role of thyroid dysfunction in the relationship between insomnia and osteoporosis: A Mendelian...

Insomnia and osteoporosis are both prevalent conditions with rising incidence. Observational studies have suggested that insomnia may lead to thyroid dysfunction, which in turn contributes to osteoporosis. However, the interplay among these three conditions remains unexamined. This study aimed to investigate the causal association between insomnia and osteoporosis, while also analyzing whether thyroid dysfunction mediates this relationship.

A two-sample Mendelian randomization approach was applied to examine the genetic association between insomnia and osteoporosis. Mediator MR was subsequently used to assess the intermediary role of thyroid dysfunction. The inverse variance weighting method served as the primary analytical strategy. Heterogeneity was evaluated using MR-Egger's intercept, Cochran's Q test, and leave-one-out analysis. The MR-PRESSO test was conducted to assess horizontal pleiotropy. To ensure robustness, FDR correction was applied.

A genetic association between insomnia and osteoporosis was observed (IVW: OR = 1.004, p = 0.007). Insomnia showed a genetic link with hypothyroidism (IVW: OR = 1.010, p = 0.00075), but not with hyperthyroidism, Hashimoto's thyroiditis, or Graves' disease (p > 0.05). Mediator MR revealed that hypothyroidism accounted for 6.29 % (6.27 %-6.31 %) of the effect of insomnia on osteoporosis.

This study supports a causal link between insomnia and osteoporosis. Hypothyroidism plays a mediating role in this pathway. Targeting hypothyroidism may lower the risk of osteoporosis associated with insomnia.