Objective:To investigate the correlation between thyroid dysfunction(including hyperthyroidism and hypothyroidism)and knee osteoarthritis(KO A)using Mendelian randomization(MR)analysis.Methods:Genome-wide association studies(GWAS)data for hyperthyroidism,hypothyroidism,and KOA from the IEU GWAS database at the University of Bristol was collected.By setting association strength and eliminating linkage imbalance,single nucleotide polymorphisms(SNPs)were selected as instrumental variables(IVs).In the forward MR analysis,the study used hyperthyroidism and hypothyroidism as exposures,and obtained 5 and 28 SNPs as IVs,respectively,with KOA as the outcome.In reverse MR analysis,six SNPs were obtained as IVs using KOA as exposure,with hyperthyroidism or hypothyroidism as outcomes.Bidirectional MR analysis uses inverse variance weighting(IVW)as the primary analysis method,and the other four methods(weighted mode,weighted median,simple mode,MR Egger)as auxiliary analyses to evaluate the causal relationship between thyroid dysfunction and KOA.Heterogeneity and pleiotropy tests were also used,and the stability of the results was evaluated using the retention method.Results:Genetic prediction of hyperthyroidism was associated with an increased risk of KOA(IVW:OR=1.048,95％CI 1.026-1.070,P＜0.001).No evidence was found of causal relationships for hypothyroidism on KOA(IVW:OR=1.029,95％CI 0.983-1.077,P=0.221),as well as KOA on hyperthyroidism(IVW:OR=0.748,95％CI 0.205-2.736,P=0.661)and KOA on hypothyroidism(IVW:OR=0.997,95％CI 0.646-1.539,P=0.989).Conclusion:This result indicates a causal relationship between hyperthyroidism and KOA,and no causal relationship was found in the study and reverse study of hypothyroidism on KOA.The findings of this study require further validation through laboratory research,as well as evidence support from future studies with larger sample sizes.
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