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

HU Tian; LI Wenshen; YI Shanghui; LIU Ying

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Journal of Hunan Normal University(Medical Science) ›› 2025, Vol. 22 ›› Issue (6) : 110-117.

Clinical Medicine

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

HU Tian, LI Wenshen, YI Shanghui, LIU Ying

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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.

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gastroesophageal reflux disease / bronchiectasis / mendelian randomization / causal inference / mediating effect

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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

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