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  

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

作　　者：徐小东 王配婕 谢文鹏 李琦[1] 傅永升 王卫国[1,2] XU Xiao-dong;WANG Pei-jie;XIE Wen-peng;LI Qi;FU Yong-sheng;WANG Wei-guo

机构地区：[1]山东中医药大学,山东济南250300 [2]山东中医药大学附属医院,山东济南250014

出　　处：《风湿病与关节炎》2024年第2期6-11,共6页Rheumatism and Arthritis

基　　金：国家自然科学基金青年项目(82104897);中国中医药研究促进会项目(中医促会立项[2021]8号);山东省中医药科技项目(2021M173);济南市临床医学科技创新计划项目(202019115)。

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。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 0.0015(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.

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 

分 类 号：R581.2[医药卫生—内分泌] R684.3[医药卫生—内科学]