胃食管反流病与肠易激综合征因果关系的两样本孟德尔随机化研究

翟天祺; 江振宇; 张静洁; 年媛媛; 孟宪梅

doi:10.16766/j.cnki.issn.1674-4152.004368

胃食管反流病与肠易激综合征因果关系的两样本孟德尔随机化研究

doi: 10.16766/j.cnki.issn.1674-4152.004368

包头医学院第二附属医院消化内科，内蒙古包头 014030

基金项目:

内蒙古自治区自然科学基金项目 2024ZD28

详细信息

通讯作者:
孟宪梅，E-mail：mxmxhk@163.com

中图分类号: R573 R574.4
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- 文章访问数: 5
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出版历程
- 收稿日期: 2025-09-11
- 网络出版日期: 2026-04-11

A two-sample Mendelian randomization study on the causal relationship between gastroesophageal reflux disease and irritable bowel syndrome

Department of Gastroenterology, the Second Affiliated Hospital of Baotou Medical College, Baotou, Inner Mongolia 014030, China

摘要

摘要: 目的胃食管反流病(GERD)和肠易激综合征(IBS)是最常见的胃肠道疾病，GERD、IBS对患者的日常生活、工作和心理状态产生不同程度的影响。本研究将运用孟德尔随机化(MR)探究GERD与IBS两种疾病的因果关系。方法 GERD数据、IBS数据均来自GWAS数据库，分别包括1 590 227例GERD样本，病例组462 753例，对照组1 127 474例；IBS样本486 601例，病例组53 400例，对照组433 201例，以上样本均来自欧洲人群。以IVW为主要分析方法，检验GERD与IBS二者之间的因果关系。运用IVW与MR-Egger法进行异质性检验，运用MR-Egger回归截距进行多效性检验，运用“留一法”检验研究的敏感性，使用F检验是否存在弱工具变量偏倚。结果选择GERD为暴露，以IBS为结局时，筛选并纳入191例SNP，结果提示GERD是增加IBS发生的危险因素，具有一定的因果联系(IVW法：OR=1.328，95% CI：1.269~1.390，P < 0.05)，进行反向MR分析得出，IBS同样会增加发生GERD的风险(IVW法：OR=1.453，95% CI：1.092~1.932，P < 0.05)。结论 GERD与IBS存在双向因果关系，GERD的存在会增加IBS的风险，而IBS同样对GERD具有正向作用。
- 胃食管反流病 /
- 肠易激综合征 /
- 孟德尔随机化
Abstract: Objective Gastroesophageal reflux disease (GERD) and irritable bowel syndrome (IBS) are the most common gastrointestinal diseases. GERD and IBS have different degrees of impact on patients ' daily life, work and psychological state. This study aims to explore the causal relationship between GERD and IBS using Mendelian randomization (MR). Methods GERD data and IBS data were all from the GWAS database, including 1 590 227 GERD samples (462 753 cases in the case group and 1 127 474 cases in the control group) and 486 601 cases of IBS samples (53 400 cases in the case group and 433 201 cases in the control group). The above samples were all from the European population. IVW was used as the main analysis method to test the causal relationship between GERD and IBS. IVW and MR-Egger methods were used to test heterogeneity, MR-Egger regression intercept was used to test pleiotropy, "leave one" method was used to test the sensitivity of the study, and F value was used to test whether there was weak instrumental variable bias. Results When GERD was selected as exposure and IBS was used as the outcome, 191 cases of SNPs were screened and included. Results indicated that GERD was a risk factor for the occurrence of IBS, and there was a certain causal relationship (IVW method: OR=1.328, 95% CI: 1.269-1.390, P < 0.05). Reverse MR analysis showed that IBS also increased the risk of GERD (IVW method: OR=1.453, 95% CI: 1.092-1.932, P < 0.05). Conclusion There is a bidirectional causal relationship between GERD and IBS. The GERD increases the risk of IBS, and IBS also has a positive effect on GERD.
- Gastroesophageal reflux disease /
- Irritable bowel syndrome /
- Mendelian randomization

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图 1 孟德尔随机化研究设计

Figure 1. Schematic of two-sample MR analysis

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图 2 GERD与IBS散点图分析结果

Figure 2. Scatter plot of causality between Gastroesophageal reflux disease and Irritable bowel syndrome

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图 3 GERD与IBS漏斗图分析结果

Figure 3. Funnel-plot of causality between Gastroesophageal reflux disease and Irritable bowel syndrome

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图 4 GERD与IBS“留一法”图分析结果

Figure 4. Leave one out sensitivity analysis results of Gastroesophageal reflux disease and Irritable bowel syndrome

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图 5 GERD与IBS森林图分析结果

Figure 5. Forest plot analysis results of Gastroesophageal reflux disease and Irritable bowel syndrome

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表 1 GERD与IBS孟德尔随机化分析结果

Table 1. Results of GERD and IBS MR analysis

暴露	结局	方法	SNPs	β	SE	OR(95% CI)	P值
GERD	IBS	MR-Egger	191	0.237	0.121	1.268(0.999~1.607)	0.052
		Weighted median	191	0.259	0.028	1.296(1.226~1.370)	< 0.001
		Inverse variance weighted	191	0.283	0.023	1.328(1.269~1.390)	< 0.001
		Simple mode	191	0.262	0.092	1.299(1.083~1.559)	0.005
		Weighted mode	191	0.251	0.079	1.286(1.102~1.501)	0.002
IBS	GERD	MR-Egger	3	-3.012	1.180	0.049(0.005~0.500)	0.238
		Weighted median	3	0.331	0.098	1.392(1.150~1.687)	0.007
		Inverse variance weighted	3	0.373	0.146	1.453(1.092~1.932)	0.010
		Simple mode	3	0.477	0.179	1.611(1.134~2.288)	0.117
		Weighted mode	3	0.247	0.179	1.280(0.901~1.818)	0.303

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表 2 GERD和IBS之间的异质性分析

Table 2. Heterogeneity analyses between GERD and IBS

暴露	结局	方法	Q值	P值
GERD	IBS	MR-Egger	249.043	< 0.001
		Inverse variance weighted	294.284	< 0.001
IBS	GERD	MR-Egger	0.400	0.527
		Inverse variance weighted	8.666	0.013

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表 3 GERD和IBS之间的水平多效性分析

Table 3. Horizontal pleiotropy analyses between GERD and IBS

暴露	结局	方法	截距	SE	P值
GERD	IBS	MR-Egger	0.001	0.004	0.694
IBS	GERD	MR-Egger	0.141	0.049	0.213

下载: 导出CSV

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