可改变危险因素介导胃食管反流对支气管扩张的孟德尔随机化研究

胡添; 李文晟; 易尚辉; 刘颖

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湖南师范大学学报医学版 ›› 2025, Vol. 22 ›› Issue (6) : 110-117.

临床医学

可改变危险因素介导胃食管反流对支气管扩张的孟德尔随机化研究

胡添, 李文晟, 易尚辉, 刘颖

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Mendelian Randomization of Bronchiectasis with Modifiable Risk Factors Mediated by Gastroesophageal Reflux

HU Tian, LI Wenshen, YI Shanghui, LIU Ying

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摘要

目的为阐明胃食管反流病与支气管扩张的因果关系,使用多种孟德尔随机化（Mendelian randomization,MR）,评估可改变的支气管扩张危险因素在致病途径中的潜在中介作用。方法胃食管反流病和支气管扩张的汇总数据,均来自公共全基因组关联研究（genome-wide association studies,GWAS）项目。单核苷酸多态性（single nucleotide polymorphisms,SNP）用作工具变量。采用5种互补的孟德尔随机化方法,包括逆方差加权（inverse variance weighting,IVW）、MR-Egger、加权中位数、加权模式和简单模式方法。IVW方法被认为是主要方法。此外,还进行了敏感性分析,包括 Cochran Q 检验、MR-Egger 截距检验和留一法分析,以评估结果的稳健性。采用多种孟德尔随机化分析来评估胃食管反流病和支气管扩张之间的因果关系,并对筛选得到的SNP进行功能注释,明确其生物意义。结果根据IVW结果,研究认为胃食管反流病与支气管扩张之间存在因果关系（OR=1.25,95%CI：1.02~1.52）。进一步的中介分析表明,嗜酸性粒细胞和类风湿关节炎介导了胃食管反流病对支气管扩张影响的4.9% 和50.4%。敏感性分析表明,因果估计是稳健的。结论基因预测的胃食管反流病与支气管扩张风险之间存在因果关系,并且部分由类风湿关节炎以及嗜酸性粒细胞介导。

Abstract

Objectives To elucidate the causal relationship between gastroesophageal reflux disease (GERD) and bronchiectasis (BE), studies were analyzed using a variety of Mendelian randomization methods and to assess the potential mediating role of modifiable risk factors for bronchiectasis in the pathogenesis. Methods Pooled data on GERD and BE were obtained from publicly available genome-wide association studies (GWAS). Single nucleotide polymorphisms (SNPs) were utilized as instrumental variables. Five complementary MR methods were employed, including inverse variance weighting (IVW), MR-Egger, weighted median, weighted mode, and simple mode methods. IVW was the primary method. Additionally, sensitivity analyses, such as Cochran's Q test, MR-Egger intercept test, and leave-one-out analysis, were conducted to assess the robustness of the findings. Two-sample univariate Mendelian randomization and two-step Mendelian randomization analyses were performed to evaluate the causal relationship between GERD and BE. Results Based on the inverse variance-weighted (IVW) analysis, we concluded that there is a significant causal relationship between GERD and BE (OR=1.25, 95% CI: 1.02-1.52). Further mediation analysis indicated that eosinophils and rheumatoid arthritis mediate 4.9% and 50.4% of the effect of GERD on BE, respectively. Sensitivity analyses confirmed the robustness of this causal estimation. Conclusions There exists a causal relationship between genetically predicted GERD and the risk of bronchiectasis, which is partially mediated by rheumatoid arthritis and eosinophil activity.

导出引用

胡添, 李文晟, 易尚辉, 刘颖. 可改变危险因素介导胃食管反流对支气管扩张的孟德尔随机化研究[J]. 湖南师范大学学报医学版. 2025, 22(6): 110-117

HU Tian, LI Wenshen, YI Shanghui, LIU Ying. Mendelian Randomization of Bronchiectasis with Modifiable Risk Factors Mediated by Gastroesophageal Reflux[J]. Journal of Hunan Normal University(Medical Science). 2025, 22(6): 110-117

中图分类号： R57 R562.22

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