{"title":"Modifiable factors for irritable bowel syndrome: evidence from Mendelian randomisation approach.","authors":"Di Liu, Meiling Cao, Shanshan Wu, Yiwen Jiang, Weijie Cao, Tengfei Lin, Fuxiao Li, Feng Sha, Zhirong Yang, Jinling Tang","doi":"10.1136/egastro-2024-100126","DOIUrl":null,"url":null,"abstract":"<p><strong>Abstract: </strong></p><p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>Genetic correlation and Mendelian randomisation (MR) analyses were integrated to identify potential modifiable factors and coexisting disorders linked to IBS. Subsequently, multiresponse MR (MR<sup>2</sup>) 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<sup>2</sup> analysis, coexisting disorders were also treated as outcomes alongside IBS.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"3 1","pages":"e100126"},"PeriodicalIF":0.0000,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770431/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"eGastroenterology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1136/egastro-2024-100126","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Abstract:
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 (MR2) 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 MR2 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.
摘要:背景:影响肠易激综合征(IBS)的潜在可改变因素尚未被彻底记录。我们旨在系统地调查与肠易激综合征相关的可改变因素,同时考虑未观察到的混杂因素和共存疾病的影响。方法:结合遗传相关性和孟德尔随机化(MR)分析,确定与肠易激综合征相关的潜在可改变因素和共存疾病。随后,采用多反应磁共振(MR2)进一步检查这些关联。使用了汇总水平的全基因组关联数据。根据队列研究和荟萃分析的证据,确定了可改变的因素和共存的疾病(即胃肠道和精神疾病)。在所有的分析中,IBS是主要结局,而在MR2分析中,共存的疾病也被视为IBS的结局。结果:大多数已确定的可改变因素和共存疾病与肠易激综合征表现出遗传相关性。磁共振分析显示肠易激综合征与多部位慢性疼痛(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)、积极情绪(OR=0.30, 95% CI 0.24至0.37)、神经质评分(OR=1.20, 95% CI 1.16至1.25)和抑郁(OR=1.50, 95% CI 1.37至1.66)之间存在很强的因果关系。此外,吸烟、饮酒频率、大专或大学学历、智力、儿童虐待、虚弱指数、肠憩室疾病和精神分裂症与肠易激综合征呈正相关。多部位慢性疼痛与肠易激综合征和共存疾病之间存在明显关联。结论:我们的研究确定了一系列与肠易激综合征相关的潜在可改变因素和共存疾病,并得到遗传证据的支持,包括遗传相关性和多次MR分析。多部位慢性疼痛的存在可能为同时预防肠易激综合征及其共存疾病提供了一条有希望的途径。