基于孟德尔随机化探究甲状腺功能减退症与多种结缔组织疾病的因果关系OA

Objective:To explore the causal relationship between hypothyroidism and systemic lupus erythematosus,dermatomyositis,rheumatoid arthritis,and mixed connective tissue diseases using Mendelian randomization(MR)algorithm.Methods:Single nucleotide polymorphisms(SNPs)associated with hypothyroidism were selected from genome-wide association study data(GWAS)based on corresponding thresholds,and evaluated using inverse variance weighted(IVW),MR-Egger regression,weighted median,simple mode,and weighted mode to explore the risk association between hypothyroidism and various connective tissue diseases.At the same time,Cochran Q method was used to evaluate the heterogeneity of SNPs,and MR-Egger intercept was used to test the horizontal pleiotropy of SNPs.The"Leave-One-Out"sensitivity analysis was used to verify whether the MR results were affected by a single SNP.Results:Hypothyroidism is a risk factor for various connective tissue diseases.The IVW model shows that hypothyroidism is a risk factor for systemic lupus erythematosus(OR=1.612),dermatomyositis(OR=2.410),rheumatoid arthritis(OR=1.004),and mixed connective tissue diseases(OR=1.078).The P-values of the intercept term in MR-Egger regression are all greater than 0.05,indicating that the SNPs used do not have gene pleiotropy,and the results of this study are reliable;the P-values of the heterogeneity test results are all greater than 0.05,indicating that there is no heterogeneity among the screened SNPs;the sensitivity analysis of the"Leave-One-Out"shows that causal associations are not affected by the effects of a single SNP.Conclusion:Genetic studies have shown that hypothyroidism increases the risk of systemic lupus erythematosus,dermatomyositis,rheumatoid arthritis,and mixed connective tissue diseases.