来源：风湿病与关节炎,2024,13（2）:6-11.

基于两样本孟德尔随机化探究甲状腺功能减退症与膝骨关节炎的因果关系（临床研究）

徐小东¹，王配婕¹，谢文鹏²，李　琦¹，傅永升¹，王卫国^1,2

　　【摘　要】目的：通过两样本孟德尔随机化方法研究甲状腺功能减退症与膝骨关节炎发病风险的因果关系。方法：获取甲状腺功能减退症和膝骨关节炎的全基因组关联研究（GWAS）数据并进行汇总，两者的数据均来自欧洲人群；将单核苷酸多态性（SNP）作为工具变量（IVs）并选择敏感的SNPs进行分析，通过逆方差加权法（IVW）、加权中位数法（WME）、MR-Egger回归法进行两样本孟德尔随机化分析，将OR值作为标准评估甲状腺功能减退症与膝骨关节炎发病风险的因果关系，通过异质性和多效性检验对得到的结果进行验证。结果：共纳入27个SNPs位点作为IVs，IVW法的OR = 4.737，95%CI = ［1.038，20.524］，P = 0.038，表明甲状腺功能减退症和膝骨关节炎之间有因果关系。MR-Egger回归方程截距项为0.001 5（P = 0.775），表明该结果不受基因多效性的影响。结论：甲状腺功能减退症与膝骨关节炎存在因果关系，且膝骨关节炎的发病风险随着甲状腺功能减退症发病风险增加而增加。

　　【关键词】　膝骨关节炎；甲状腺功能减退症；孟德尔随机化研究；全基因组关联分析；工具变量；单核苷酸多态性；因果关系

Exploring the Causal Relationship Between Hypothyroidism and Knee Osteoarthritis Based on a Two Sample

Mendelian Randomization Method

XU Xiao-dong,WANG Pei-jie,XIE Wen-peng,LI Qi,FU Yong-sheng,WANG Wei-guo

　　【ABSTRACT】Objective:To investigate the causal relationship between hypothyroidism and the risk of knee osteoarthritis using a two sample Mendelian randomization method.Methods:Genome Wide Association Study（GWAS）data on hypothyroidism and knee osteoarthritis were obtained and summarized,both of which were from the European population.Single Nucleotide Polymorphisms（SNPs）were used as instrumental variables（IVs）and sensitive SNPs were selected for analysis.Two sample Mendelian randomization analysis was performed using inverse variance weighting（IVW）,weighted median（WME）,and MR Egger regression.OR values were used as criteria to evaluate the causal relationship between hypothyroidism and the risk of knee osteoarthritis.The results were validated through heterogeneity and pleiotropy tests.Results:A total of 27 SNPs loci were included as IVs,with an OR = 4.737,95%CI =［1.038,20.524］and P = 0.038 for the IVW method,indicating a causal relationship between hypothyroidism and knee osteoarthritis.The intercept term of the MR-Egger regression equation was 0.001 5（P = 0.775）,indicating that the result is not affected by gene pleiotropy.Conclusion:There is a causal relationship between hypothyroidism and knee osteoarthritis,and the risk of knee osteoarthritis increases as the risk of hypothyroidism increases.

　　【Keywords】 knee osteoarthritis;hypothyroidism;mendelian randomization research;whole genome association analysis;instrumental variables;single nucleotide polymorphism;causal relationship