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  

Exploring the Causal Relationship Between Hypothyroidism and Various Connective Tissue Diseases Based on Mendelian Randomization

作　　者：陈炳坤 成彬 陈安明 刘红伟[1] 黄延峰[1] 唐浩熙 李林海 CHEN Bing-kun;CHENG Bin;CHEN An-ming;LIU Hong-wei;HUANG Yan-feng;TANG Hao-xi;LI Lin-hai

机构地区：[1]广州医科大学附属清远医院(清远市人民医院),广东清远511518

出　　处：《风湿病与关节炎》2024年第11期1-6,36,共7页Rheumatism and Arthritis

基　　金：广东省中医药项目(20231408)。

摘　　要：目的:通过孟德尔随机化(MR)算法,探究甲状腺功能减退症与系统性红斑狼疮、皮肌炎、类风湿关节炎、混合性结缔组织病之间的因果关系。方法:根据相应的阈值从全基因组关联研究数据(GWAS)中选取与甲状腺功能减退症有关的单核苷酸多态性位点(SNPs),并采用逆方差加权法(IVW)、MR-Egger回归、加权中位数法、简单模式和加权模式进行评估,以探究甲状腺功能减退症与多种结缔组织疾病之间风险关联性。同时利用Cochran Q检验评估SNPs的异质性,使用MR-Egger截距检验SNPss的水平多效性,以“留一法”敏感性分析验证MR结果是否受单个SNP的影响。结果:甲状腺功能减退症是多种结缔组织疾病发生的危险因素。IVW模型显示,甲状腺功能减退症是系统性红斑狼疮(OR=1.612)、皮肌炎(OR=2.410)、类风湿关节炎(OR=1.004)、混合性结缔组织疾病(OR=1.078)的危险因素。MR-Egger回归截距项的P值均>0.05,表明所用的SNPs不存在基因多效性,说明本研究的结果可靠;异质性检验结果的P值均>0.05,提示所筛SNPs之间无异质性;“留一法”敏感性分析显示因果关联不受单一SNP效应的影响。结论:遗传学研究表明,甲状腺功能减退症增加系统性红斑狼疮、皮肌炎、类风湿关节炎、混合性结缔组织疾病的发生风险。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.

关 键 词：甲状腺功能减退症 结缔组织疾病 孟德尔随机化 因果关系 

分 类 号：R581.2[医药卫生—内分泌] R593.2[医药卫生—内科学]