| Objective To analyze the causal relationship between hyperthyroidism, hypothyroidism, Graves’ disease, Hashimoto thyroiditis and the risk of developing osteoporosis in an East Asian population using a two-sample Mendelian randomization method. Methods Hyperthyroidism, hypothyroidism, Graves’ disease and Hashimoto thyroiditis were the exposure factors, osteoporosis was the outcome factor, and the study population was limited to the East Asian population. 12, 10, 9, and 7 single nucleotide polymorphisms (SNPs) were obtained for inclusion in the study as instrumental variables, respectively.Inverse variance weighted (IVW), MR-Egger regression, and weighted median (WM) methods were used to analyze the causal relationship between 4 thyroid disorders and osteoporosis risk. Cochran Q-tests and funnel plots were used to detect heterogeneity, and MR-Egger regression and MR-PRESSO were used to test for horizontal pleiotropy and outliers. Results IVW analysis identified genetically predicted hyperthyroidism (OR=1.054, 95% CI: 1.013-1.097, P=0.010) and Graves’ disease (OR=1.052, 95% CI:1.019-1.086, P=0.002) were associated with a significantly increased risk of developing osteoporosis. There was a potential causal effect between Hashimoto’s thyroiditis and osteoporosis (OR=1.047, 95% CI:1.002-1.095, P=0.040). Hypothyroidism was not causally associated with the risk of developing osteoporosis (OR=1.002, 95% CI: 0.943-1.065, P=0.942). Other methods of analysis supported this conclusion. Sensitivity analyses indicated the robustness of the results. Conclusion In East Asian populations, genetically predicted hyperthyroidism and Graves’ disease were causally associated with an increased risk of developing osteoporosis, whereas a high genetic risk of hypothyroidism did not increase the risk of developing osteoporosis. |