Table_3_Obstructive sleep apnea and 19 gastrointestinal diseases: a Mendelian randomization study.xlsx

BackgroundAlterations gastrointestinal diseases (GDs) were reported in individuals with obstructive sleep apnea (OSA), however, the genetic background between OSA and GDs is still unclear.MethodsThis 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.ResultsThis MR study suggests that OSA may play a causal role inflammation-related GDs (GERD, PIVW=5.94×10-9; gastroduodenal ulcer, PIVW=1×10-4; chronic gastritis, PIVW=0.0214; ulcerative colitis, PIVW=0.0296), and gallstones (calculi of the gallbladder, PIVW=0.0429; calculi of the bile duct, PIVW=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.ConclusionThis 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.

背景：阻塞性睡眠呼吸暂停（OSA）患者中已报道存在胃肠道疾病（GDs），然而，OSA与GDs之间的遗传背景尚不明确。方法：本研究采用孟德尔随机化（MR）分析评估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、肠易激综合症、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）之间的因果效应。采用逆方差加权（IVW）方法评估因果效应的主效应模型。结果：此MR研究表明，OSA可能在炎症相关GDs（GERD，PIVW=5.94×10^-9；胃十二指肠溃疡，PIVW=1×10^-4；慢性胃炎，PIVW=0.0214；溃疡性结肠炎，PIVW=0.0296）以及胆结石（胆囊结石，PIVW=0.0429；胆管结石，PIVW=0.0068）中发挥因果作用。在考虑肥胖、2型糖尿病、吸烟和饮酒后，多变量MR（MVMR）分析确定了OSA是GERD、胃十二指肠溃疡和胆管结石的独立风险因素。反向MVMR分析显示GERD对OSA存在因果效应。此外，我们没有发现OSA的易感性与4种癌症相关。结论：此MR分析提供了遗传预测的OSA与炎症相关GDs风险升高的独立因果关系的有力证据。此外，未观察到OSA与癌症之间的因果关联。应进一步开展研究以验证我们的发现。