肠易激综合征的可改变因素：孟德尔随机化方法的证据
Modifiable factors for irritable bowel syndrome: evidence from Mendelian randomisation approach.
作者信息
Liu Di, Cao Meiling, Wu Shanshan, Jiang Yiwen, Cao Weijie, Lin Tengfei, Li Fuxiao, Sha Feng, Yang Zhirong, Tang Jinling
机构信息
Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, China.
Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, China.
出版信息
eGastroenterology. 2025 Jan 20;3(1):e100126. doi: 10.1136/egastro-2024-100126. eCollection 2025 Jan.
BACKGROUND
The potential modifiable factors influencing irritable bowel syndrome (IBS) have not been thoroughly documented. We aimed to systematically investigate the modifiable factors associated with IBS, while accounting for the impact of unobserved confounders and coexisting disorders.
METHODS
Genetic correlation and Mendelian randomisation (MR) analyses were integrated to identify potential modifiable factors and coexisting disorders linked to IBS. Subsequently, multiresponse MR (MR) was employed to further examine these associations. Summary-level genome-wide association data were used. Modifiable factors and coexisting disorders (ie, gastrointestinal and psychiatric disorders) were identified based on evidence from cohort studies and meta-analysis. In all analyses, IBS was the primary outcome, while in the MR analysis, coexisting disorders were also treated as outcomes alongside IBS.
RESULTS
Most identified modifiable factors and coexisting disorders exhibited genetic correlations with IBS. MR analyses revealed strong causation between IBS and multisite chronic pain (OR=2.20, 95% CI 1.82 to 2.66), gastro-oesophageal reflux disease (OR=1.31, 95% CI 1.23 to 1.39), well-being spectrum (OR=0.17, 95% CI 0.13 to 0.21), life satisfaction (OR=0.31, 95% CI 0.25 to 0.38), positive affect (OR=0.30, 95% CI 0.24 to 0.37), neuroticism score (OR=1.20, 95% CI 1.16 to 1.25) and depression (OR=1.50, 95% CI 1.37 to 1.66). Additionally, smoking, alcohol frequency, college or university degree, intelligence, childhood maltreatment, frailty index, diverticular disease of the intestine and schizophrenia were suggestively associated with IBS. Robust associations were found between multisite chronic pain and both IBS and coexisting disorders.
CONCLUSIONS
Our study identified a comprehensive array of potential modifiable factors and coexisting disorders associated with IBS, supported by genetic evidence, including genetic correlation and multiple MR analyses. The presence of multisite chronic pain may offer a promising avenue for the concurrent prevention of IBS and its coexisting disorders.
背景
影响肠易激综合征（IBS）的潜在可改变因素尚未得到充分记录。我们旨在系统地研究与IBS相关的可改变因素，同时考虑未观察到的混杂因素和共存疾病的影响。
方法
整合遗传相关性和孟德尔随机化（MR）分析，以确定与IBS相关的潜在可改变因素和共存疾病。随后，采用多反应MR（MR）进一步检验这些关联。使用汇总水平的全基因组关联数据。基于队列研究和荟萃分析的证据确定可改变因素和共存疾病（即胃肠道和精神疾病）。在所有分析中，IBS是主要结局，而在MR分析中，共存疾病也与IBS一起被视为结局。
结果
大多数确定的可改变因素和共存疾病与IBS存在遗传相关性。MR分析显示IBS与多部位慢性疼痛（OR=2.20，95%CI 1.82至2.66）、胃食管反流病（OR=1.31，95%CI 1.23至1.39）、幸福感谱（OR=0.17，95%CI 0.13至0.21）、生活满意度（OR=0.31，95%CI 0.25至0.38）、积极情感（OR=0.30，95%CI 0.24至0.37）、神经质得分（OR=1.20，95%CI 1.16至1.25）和抑郁症（OR=1.50，95%CI 1.37至1.66）之间存在强因果关系。此外，吸烟、饮酒频率、大学学历、智力、童年虐待、衰弱指数、肠道憩室病和精神分裂症与IBS存在提示性关联。多部位慢性疼痛与IBS和共存疾病之间均发现了稳健的关联。
结论
我们的研究在遗传证据（包括遗传相关性和多项MR分析）的支持下，确定了一系列与IBS相关的潜在可改变因素和共存疾病。多部位慢性疼痛的存在可能为同时预防IBS及其共存疾病提供一个有前景的途径。
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