基于两样本双向孟德尔随机化的甲状腺功能亢进症和骨质疏松症因果关系研究OA

Objective To evaluate the causal relationship between hyperthyroidism and osteoporosis using a two-sample bidirectional Mendelian randomization(MR)approach.Methods Large-scale genome-wide association study(GWAS)data from European populations were used.Hyperthyroidism summary statistics were obtained from the UK Biobank(GWAS ID:UKB-B-20289,n=462 933,2018)and osteoporosis data were derived from the European Bioinfor-matics Institute(EBI)GWAS database(GWAS ID:ebi-a-GCST90038656,n=484 598,2021).Statistical analysis was performed using R software(version 4.4.0).The inverse variance weighted(IVW)method served as the primary analyti-cal approach,supplemented by MR-Egger regression,weighted median and other complementary MR methods.Reverse MR analysis was conducted to exclude potential reverse causality.Heterogeneity,sensitivity and horizontal pleiotropy ana-lyses were further performed to ensure the robustness of the findings.Results Forward MR analysis showed that hyperthy-roidism significantly increased the risk of osteoporosis(IVW:OR=1.158,95%CI:1.050-1.277,P=0.0033),and the results were consistent across different MR methods.The MR-Egger intercept was not statistically significant(P=0.837),indicating no substantial horizontal pleiotropy.Reverse MR analysis demonstrated no significant causal effect of osteoporosis on hyperthyroidism(IVW:OR=1.028,95%CI:0.976-1.083,P=0.292)and sensitivity analyses showed no notable abnormalities.Conclusion Hyperthyroidism can increase the risk of osteoporosis,while osteoporosis exerts no reverse causal effect on hyperthyroidism.Future research can combine metabolomics and molecular mechanism studies to further clarify its biological basis,thereby providing a reference for the prevention and management of osteoporosis.