Gastroesophageal reflux disease and idiopathic pulmonary fibrosis risk: A mendelian randomization study

IF 0.7 4区医学

European Journal of Inflammation Pub Date : 2024-04-16 DOI:10.1177/1721727x241247761

Minjie Lin, Junjie Wang, Jie Wei, Yu Yao, Cheng Tang, Wenfang Jin, Weihong Yuan, Yanling Lv

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Abstract

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with unknown etiology and treatment options for it were limited. Whether Gastroesophageal reflux disease (GERD) could affect the occurrence of IPF remains unclear.Methods: Using available data from FINNGEN and IEU OpenGWAS, we performed Two-sample mendelian randomization (MR) to explore the causal relationship between GERD and IPF.Results: Using 65 GERD-related SNPs, we found the association between GERD and the risk of IPF was not statistically significant with IVW approach (OR = 1.20, 95% CI = 0.84-1.70, p = .32), MR-Egger regression (OR = 1.65, 95% CI = 0.19-14.43, p = .65) and weighted median approaches (OR = 1.44, 95% CI = 0.94-2.23, p = .09). However, heterogeneity was observed with MR-Egger ( p = .001) and IVW ( p = .001) analysis. Similar results were obtained with MR-PRESSO (global heterogeneity test p value <.01). After removing one outlier (rs9636202), with weighted median method, we found GERD increased the risk of IPF (OR 1.55, 95% CI: 1.01-2.36, p = .045) while not with the IVW (OR: 1.27, 95% CI: 0.91-1.78, p = .16) and MR-Egger method (OR: 2.01, 95% CI: 0.26-15.8, p = .51). Hence, we set a stricter instrument p value threshold to a level of <1 × 10−8, there was no statistical significance with MR estimates. Additionally, there was no directional pleiotropy observed (intercept = −0.01; SE = 0.036. p = .772). To validate causal effect of GERD on IPF, we identified three SNPs (rs79348626, rs12759463 and rs4269485) from another GWAS data that were significantly associated with GERD independently. The analysis showed no evidence of causality between GERD and IPF using the IVW method (OR = 0.91, 95% CI = 0.42-1.97, p = .814), MR-Egger regression (OR = 0.43, 95% CI = 0.06-3.07, p = .553) and weighted median approaches (OR = 0.90, 95% CI = 0.36-2.27, p = 0 0.819).Conclusions: Our analysis using MR does not support GERD could significantly increase the incidence of IPF, which suggests that treating GERD cannot reduce the risk of developing IPF.

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胃食管反流病与特发性肺纤维化风险：泯灭随机研究

背景：特发性肺纤维化（IPF）是一种进展性间质性肺病，病因不明，治疗方案有限。胃食管反流病（GERD）是否会影响 IPF 的发生仍不清楚：利用 FINNGEN 和 IEU OpenGWAS 的现有数据，我们采用双样本泯灭随机法（MR）探讨了胃食管反流病与 IPF 之间的因果关系：使用 65 个胃食管反流相关 SNPs，我们发现胃食管反流与 IPF 风险之间的关系在 IVW 方法（OR = 1.20，95% CI = 0.84-1.70，p = .32）、MR-Egger 回归（OR = 1.65，95% CI = 0.19-14.43，p = .65）和加权中位数方法（OR = 1.44，95% CI = 0.94-2.23，p = .09）下均无统计学意义。然而，MR-Egger（P = .001）和 IVW（P = .001）分析也发现了异质性。MR-PRESSO 也得到了类似的结果（总体异质性检验 p 值 <.01）。剔除一个离群值（rs9636202）后，采用加权中值法，我们发现胃食管反流病增加了患 IPF 的风险（OR 1.55，95% CI：1.01-2.36，p = .045），而 IVW 法（OR：1.27，95% CI：0.91-1.78，p = .16）和 MR-Egger 法（OR：2.01，95% CI：0.26-15.8，p = .51）则没有增加患 IPF 的风险。因此，我们设置了更严格的仪器 p 值阈值，即 1 × 10-8，MR 估计值没有统计学意义。此外，也没有观察到方向性多效应（截距 = -0.01；SE = 0.036；P = .772）。为了验证胃食管反流病对 IPF 的因果效应，我们从另一个 GWAS 数据中发现了三个 SNPs（rs79348626、rs12759463 和 rs4269485）与胃食管反流病有显著的独立相关性。使用 IVW 法（OR = 0.91，95% CI = 0.42-1.97，p = .814）、MR-Egger 回归法（OR = 0.43，95% CI = 0.06-3.07，p = .553）和加权中位法（OR = 0.90，95% CI = 0.36-2.27，p = 0 0.819）进行的分析表明，没有证据表明胃食管反流病与 IPF 之间存在因果关系：我们使用 MR 进行的分析不支持胃食管反流病可显著增加 IPF 的发病率，这表明治疗胃食管反流病不能降低 IPF 的发病风险。

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European Journal of Inflammation Medicine-Immunology and Allergy

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期刊介绍： European Journal of Inflammation is a multidisciplinary, peer-reviewed, open access journal covering a wide range of topics in inflammation, including immunology, pathology, pharmacology and related general experimental and clinical research.