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阻塞性睡眠呼吸暂停与19种胃肠道疾病:一项孟德尔随机化研究。

Obstructive sleep apnea and 19 gastrointestinal diseases: a Mendelian randomization study.

作者信息

Yan Weiheng, Zhou Jiayi, Jiang Miaomiao, Kong Yaru, Qin Han, Qi Yuwei, Wang Shan, Tai Jun

机构信息

Department of Otolaryngology, Head and Neck Surgery, Children's Hospital Capital Institute of Pediatrics, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Peking University Sixth Hospital, Peking University Institute of Mental Health, Beijing, China.

出版信息

Front Psychiatry. 2024 Jul 26;15:1256116. doi: 10.3389/fpsyt.2024.1256116. eCollection 2024.

Abstract

BACKGROUND

Alterations gastrointestinal diseases (GDs) were reported in individuals with obstructive sleep apnea (OSA), however, the genetic background between OSA and GDs is still unclear.

METHODS

This investigation employed Mendelian randomization (MR) analyses to evaluate the causal effect between OSA and 19 types of GDs (gastroesophageal reflux disease (GERD), ulcerative colitis, celiac disease, Crohn's disease, chronic gastritis, irritable bowel syndrome, primary biliary cholangitis, diverticular disease, gastroduodenal ulcer, acute pancreatitis, non-alcoholic fatty liver disease, primary sclerosing cholangitis, cirrhosis, calculus of bile duct, calculus of gallbladder, pancreatic cancer, gastric cancer, colorectal cancer, and esophageal cancer). The inverse-variance weighted (IVW) method was used to evaluate the main effects model of causality.

RESULTS

This MR study suggests that OSA may play a causal role inflammation-related GDs (GERD, P=5.94×10; gastroduodenal ulcer, P=1×10; chronic gastritis, P=0.0214; ulcerative colitis, P=0.0296), and gallstones (calculi of the gallbladder, P=0.0429; calculi of the bile duct, P=0.0068). After accounting for obesity, type 2 diabetes, smoking, and alcohol consumption, the multivariate MR (MVMR) analysis identified that OSA is an independent risk factor for GERD, gastroduodenal ulcer, and calculus of the bile duct. The reverse MVMR analysis showed a causal effect of GERD on OSA. Besides, we did not find that the predisposition to OSA was associated with 4 cancers.

CONCLUSION

This MR analysis provides compelling evidence of an independent causal relationship between genetically predicted OSA and an elevated risk of inflammation-related GDs. Besides, no causal association was observed between OSA and cancers. Further studies should be carried out to verify our findings.

摘要

背景

阻塞性睡眠呼吸暂停(OSA)患者中报告了胃肠道疾病(GDs)的改变,然而,OSA与GDs之间的遗传背景仍不清楚。

方法

本研究采用孟德尔随机化(MR)分析来评估OSA与19种GDs(胃食管反流病(GERD)、溃疡性结肠炎、乳糜泻、克罗恩病、慢性胃炎、肠易激综合征、原发性胆汁性胆管炎、憩室病、胃十二指肠溃疡、急性胰腺炎、非酒精性脂肪性肝病、原发性硬化性胆管炎、肝硬化、胆管结石、胆囊结石、胰腺癌、胃癌、结直肠癌和食管癌)之间的因果关系。采用逆方差加权(IVW)方法评估因果关系的主要效应模型。

结果

本MR研究表明,OSA可能在炎症相关的GDs(GERD,P = 5.94×10;胃十二指肠溃疡,P = 1×10;慢性胃炎,P = 0.0214;溃疡性结肠炎,P = 0.0296)和胆结石(胆囊结石,P = 0.0429;胆管结石,P = 0.0068)中起因果作用。在考虑肥胖、2型糖尿病、吸烟和饮酒因素后,多变量MR(MVMR)分析确定OSA是GERD、胃十二指肠溃疡和胆管结石的独立危险因素。反向MVMR分析显示GERD对OSA有因果效应。此外,我们未发现OSA的易感性与4种癌症有关。

结论

本MR分析提供了有力证据,证明基因预测的OSA与炎症相关GDs风险升高之间存在独立的因果关系。此外,未观察到OSA与癌症之间存在因果关联。应开展进一步研究以验证我们的发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f8d/11310136/615a89d8fa13/fpsyt-15-1256116-g001.jpg

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