首页|基于孟德尔随机化分析探讨类风湿关节炎与肺动脉高压的因果关系

基于孟德尔随机化分析探讨类风湿关节炎与肺动脉高压的因果关系

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目的 通过孟德尔随机化设计方法探讨类风湿关节炎(RA)与肺动脉高压(PH)的因果关系。方法 使用公开的全基因组关联研究获取暴露与结局的单核苷酸多态性(SNPs)数据进行汇总分析。使用逆方差加权法(IVW)作为主要分析方法评估暴露因素(RA)对结局(PH)的因果效应。以MR-Egger回归法、加权中位数法(WM)、加权模式和简单模式作为回归补充说明,进行敏感性分析评估结果的稳健性;采用"heterogenei-ty"函数计算P值检验异质性,采用"horizontal pleiotropy"函数计算P值检验水平多效性。结果 在GWAS数据库中收录的"FINNGEN数据"中选择出的SNPs经孟德尔随机分析去除连锁不平衡且满足P<5×10-8,具有强相关性;通过整合暴露因素与结局获取了有效工具变量。IVW结果显示,RA是PH的风险因素(OR=1。295,95%CI:1。053~1。593,P=0。014)。"heterogeneity"函数检验表明结果不存在异质性(P=0。221);"horizontal pleiotropy"函数检验表明结果不存在水平多效性(P=0。877),总体结果稳健可靠。结论 RA是PH的危险因素,RA与PH存在正向关联。
Study on causal relationship between rheumatoid arthritis and pulmonary hypertension based on Mendelian randomization
Objective To investigate the causal relationship between rheumatoid arthritis (RA) and pulmonary hypertension (PH) by the Mendelian randomization design method.Methods The data on single nucleotide polymorphisms (SNPs) of exposure and outcome were obtained by using publicly available ge-nome-wide association studies and the summary analysis was conducted;the inverse variance-weighted (IVW) method as the primary analysis method was used to assess the causal effect of exposure factors (RA) on the outcomes (PH);the MR-Egger regression method,weighted median method (WM),weighted model and sim-ple model were used as supplementary regression explanations to conduct the sensitivity analysis for evalua-ting the robustness of results;the "heterogeneity" function was used to calculate the "P value" for testing the heterogeneity,and the "horizontal pleiotropy" function was used to calculate the "P value" to test the level pleiotropy.Results In the "FINNGEN data" included in the GWAS database,the SNPs had the strong corre-lation after removing the linkage imbalance by Mendelian random analysis and satisfying "P<5×10-8" were selected,the effective instrumental variables were obtained by integrating the exposure and outcome.The IVW results showed that RA was a risk factor for PH (OR=1.295,95%CI:1.053-1.593,P=0.014)."heteroge-neity" function test showed that the results had no heterogeneity (P=0.221);" horizontal pleiotropy" func-tion test showed that the results had no horizontal pleiotropy (P=0.877),and the total results were steady and reliable.Conclusion RA is a risk factor for PH,and RA is positively associated with PH.

rheumatoid arthritispulmonary hypertensionMendelian randomization analysiscausal association

王勇、姚晓玲、凌益、杨豫正、马武开

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贵州中医药大学第二附属医院风湿免疫科,贵阳 550001

类风湿关节炎 肺动脉高压 孟德尔随机化分析 因果关联

国家自然科学基金项目贵州省中医风湿免疫病临床研究中心项目

82274678黔科合平台人才[2020]2202

2024

重庆医学
重庆市卫生信息中心,重庆市医学会

重庆医学

CSTPCD
影响因子:1.797
ISSN:1671-8348
年,卷(期):2024.53(16)