{"title":"炎症因子与炎症性肠病的因果关系:一项双向孟德尔随机化研究结合meta分析。","authors":"Xiang Ji, Afen Wu, Dehua Zha, Ming Li","doi":"10.1097/MD.0000000000042988","DOIUrl":null,"url":null,"abstract":"<p><p>Due to the limitations of traditional observational studies, investigating the association between inflammatory factors and inflammatory bowel disease (IBD) remains challenging. In this study, we employed Mendelian randomization (MR) combined with meta-analysis to assess the causal relationship between 91 inflammatory factors and IBD. We selected genome-wide association study (GWAS) data for inflammatory factors and IBD from GWAS databases and conducted 2-sample MR analyses using the inverse-variance weighted (IVW) method, MR-Egger regression, and weighted median estimator. The MR analyses were performed for 91 inflammatory factors with IBD outcome data from 2 different databases. Subsequently, a meta-analysis of the main IVW results was conducted, followed by multiple corrections of the meta-analysis results. Conduct MR analysis between inflammatory factors and subtypes of IBD (Crohn disease and ulcerative colitis [UC]), followed by reverse causality validation of positive inflammatory factors with IBD and its subtype outcome data. In the IVW analysis of the 91 inflammatory factors with IBD outcome data from the GWAS catalog database, C-X-C motif chemokine 9 (CXCL9) was found to be positively associated with the risk of IBD (OR = 1.24, 95% CI = 1.09-1.41, P = .001). Similarly, in the IVW analysis with IBD outcome data from the IEU database, CXCL9 was also positively associated with the risk of IBD (OR = 1.76, 95% CI = 1.12-2.76, P = .015). Meta-analysis and multiple corrections showed a significant association between CXCL9 and IBD (OR = 1.27, 95% CI = 1.12-1.44, P = .001). In the MR analysis of IBD subtypes, the inflammatory factor CXCL9 showed a significant causal association with UC using the IVW method (OR = 1.77, 95% CI = 1.39-2.44, P = .0004), with a P-value of .038 after multiple testing correction. However, no significant causal association was observed between CXCL9 and Crohn disease = 3.28). In the reverse MR analysis, no causal effect of IBD and UC on CXCL9 was found. CXCL9 exhibits a causal relationship with IBD, functioning as a disease-progression risk factor that elevates UC risk, suggesting potential therapeutic targets for alleviating symptoms and slowing progression in UC patients.</p>","PeriodicalId":18549,"journal":{"name":"Medicine","volume":"104 26","pages":"e42988"},"PeriodicalIF":1.3000,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12212840/pdf/","citationCount":"0","resultStr":"{\"title\":\"Causal relationship between inflammatory factors and inflammatory bowel disease: A bidirectional Mendelian randomization study combined with meta-analysis.\",\"authors\":\"Xiang Ji, Afen Wu, Dehua Zha, Ming Li\",\"doi\":\"10.1097/MD.0000000000042988\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Due to the limitations of traditional observational studies, investigating the association between inflammatory factors and inflammatory bowel disease (IBD) remains challenging. In this study, we employed Mendelian randomization (MR) combined with meta-analysis to assess the causal relationship between 91 inflammatory factors and IBD. We selected genome-wide association study (GWAS) data for inflammatory factors and IBD from GWAS databases and conducted 2-sample MR analyses using the inverse-variance weighted (IVW) method, MR-Egger regression, and weighted median estimator. The MR analyses were performed for 91 inflammatory factors with IBD outcome data from 2 different databases. Subsequently, a meta-analysis of the main IVW results was conducted, followed by multiple corrections of the meta-analysis results. Conduct MR analysis between inflammatory factors and subtypes of IBD (Crohn disease and ulcerative colitis [UC]), followed by reverse causality validation of positive inflammatory factors with IBD and its subtype outcome data. In the IVW analysis of the 91 inflammatory factors with IBD outcome data from the GWAS catalog database, C-X-C motif chemokine 9 (CXCL9) was found to be positively associated with the risk of IBD (OR = 1.24, 95% CI = 1.09-1.41, P = .001). Similarly, in the IVW analysis with IBD outcome data from the IEU database, CXCL9 was also positively associated with the risk of IBD (OR = 1.76, 95% CI = 1.12-2.76, P = .015). Meta-analysis and multiple corrections showed a significant association between CXCL9 and IBD (OR = 1.27, 95% CI = 1.12-1.44, P = .001). In the MR analysis of IBD subtypes, the inflammatory factor CXCL9 showed a significant causal association with UC using the IVW method (OR = 1.77, 95% CI = 1.39-2.44, P = .0004), with a P-value of .038 after multiple testing correction. However, no significant causal association was observed between CXCL9 and Crohn disease = 3.28). In the reverse MR analysis, no causal effect of IBD and UC on CXCL9 was found. CXCL9 exhibits a causal relationship with IBD, functioning as a disease-progression risk factor that elevates UC risk, suggesting potential therapeutic targets for alleviating symptoms and slowing progression in UC patients.</p>\",\"PeriodicalId\":18549,\"journal\":{\"name\":\"Medicine\",\"volume\":\"104 26\",\"pages\":\"e42988\"},\"PeriodicalIF\":1.3000,\"publicationDate\":\"2025-06-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12212840/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/MD.0000000000042988\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICINE, GENERAL & INTERNAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/MD.0000000000042988","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
引用次数: 0
摘要
由于传统观察性研究的局限性,调查炎症因子与炎症性肠病(IBD)之间的关系仍然具有挑战性。在这项研究中,我们采用孟德尔随机化(MR)结合meta分析来评估91种炎症因子与IBD之间的因果关系。我们从GWAS数据库中选择了炎症因子和IBD的全基因组关联研究(GWAS)数据,并使用反方差加权(IVW)方法、MR- egger回归和加权中位数估计进行了2样本MR分析。MR分析来自2个不同数据库的91种炎症因子与IBD结局数据。随后,对主要IVW结果进行了荟萃分析,随后对荟萃分析结果进行了多次修正。对炎症因子与IBD亚型(克罗恩病和溃疡性结肠炎[UC])进行MR分析,然后对阳性炎症因子与IBD及其亚型结局数据进行反向因果关系验证。在对GWAS目录数据库中91种炎症因子与IBD结局数据的IVW分析中,发现C-X-C基序趋化因子9 (CXCL9)与IBD风险呈正相关(OR = 1.24, 95% CI = 1.09-1.41, P = .001)。同样,在IEU数据库IBD结局数据的IVW分析中,CXCL9也与IBD风险呈正相关(OR = 1.76, 95% CI = 1.12-2.76, P = 0.015)。荟萃分析和多次校正显示CXCL9与IBD之间存在显著相关性(OR = 1.27, 95% CI = 1.12-1.44, P = .001)。在IBD亚型的MR分析中,IVW方法显示炎症因子CXCL9与UC有显著的因果关系(OR = 1.77, 95% CI = 1.39-2.44, P = 0.0004),多次检验校正后P值为0.038。然而,CXCL9与克罗恩病之间没有明显的因果关系(3.28)。在反向MR分析中,未发现IBD和UC对CXCL9的因果关系。CXCL9与IBD表现出因果关系,作为一种升高UC风险的疾病进展危险因素,提示缓解UC患者症状和减缓UC患者进展的潜在治疗靶点。
Causal relationship between inflammatory factors and inflammatory bowel disease: A bidirectional Mendelian randomization study combined with meta-analysis.
Due to the limitations of traditional observational studies, investigating the association between inflammatory factors and inflammatory bowel disease (IBD) remains challenging. In this study, we employed Mendelian randomization (MR) combined with meta-analysis to assess the causal relationship between 91 inflammatory factors and IBD. We selected genome-wide association study (GWAS) data for inflammatory factors and IBD from GWAS databases and conducted 2-sample MR analyses using the inverse-variance weighted (IVW) method, MR-Egger regression, and weighted median estimator. The MR analyses were performed for 91 inflammatory factors with IBD outcome data from 2 different databases. Subsequently, a meta-analysis of the main IVW results was conducted, followed by multiple corrections of the meta-analysis results. Conduct MR analysis between inflammatory factors and subtypes of IBD (Crohn disease and ulcerative colitis [UC]), followed by reverse causality validation of positive inflammatory factors with IBD and its subtype outcome data. In the IVW analysis of the 91 inflammatory factors with IBD outcome data from the GWAS catalog database, C-X-C motif chemokine 9 (CXCL9) was found to be positively associated with the risk of IBD (OR = 1.24, 95% CI = 1.09-1.41, P = .001). Similarly, in the IVW analysis with IBD outcome data from the IEU database, CXCL9 was also positively associated with the risk of IBD (OR = 1.76, 95% CI = 1.12-2.76, P = .015). Meta-analysis and multiple corrections showed a significant association between CXCL9 and IBD (OR = 1.27, 95% CI = 1.12-1.44, P = .001). In the MR analysis of IBD subtypes, the inflammatory factor CXCL9 showed a significant causal association with UC using the IVW method (OR = 1.77, 95% CI = 1.39-2.44, P = .0004), with a P-value of .038 after multiple testing correction. However, no significant causal association was observed between CXCL9 and Crohn disease = 3.28). In the reverse MR analysis, no causal effect of IBD and UC on CXCL9 was found. CXCL9 exhibits a causal relationship with IBD, functioning as a disease-progression risk factor that elevates UC risk, suggesting potential therapeutic targets for alleviating symptoms and slowing progression in UC patients.
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