基于两样本孟德尔随机化法探讨胃食管反流病与睡眠障碍因果关系的研究  

Study on the causal relationship between gastroesophageal reflux disease and sleep disorder based on two sample Mendelian randomization

作　　者：刘嘉鑫 段骄 吴辉[4] 顾颖敏 冼绍祥[5] Liu Jiaxin;Duan Jiao;Wu Hui;Gu Yingmin;Xian Shaoxiang(Wuyang Outpatient Department of the Affiliated TCM Hospital of Guangzhou Medical University,Guangzhou 510130,China;Guangzhou Medical University,Guangzhou 511436,China;Geriatry Department of the First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510405,China;Cardiovascular Department of the First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510405,China;South China Institute of Cardiovascular Disease of the First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510405,China)

机构地区：[1]广州医科大学附属中医医院五羊门诊部,广州510130 [2]广州医科大学,广州511436 [3]广州中医药大学第一附属医院老年病科,广州510405 [4]广州中医药大学第一附属医院心血管科,广州510405 [5]广州中医药大学第一附属医院岭南心血管病研究所,广州510405

出　　处：《国际中医中药杂志》2024年第10期1277-1285,共9页International Journal of Traditional Chinese Medicine

基　　金：国家中医药管理局冼绍祥全国名老中医药专家传承工作室建设项目(国中医药人教函〔2022〕75号);广州市科学技术局市校(院)企联合资助项目(12440000455860170T)。

摘　　要：目的采用孟德尔随机化(MR)方法探索胃食管反流病(GERD)与睡眠障碍的因果关系,并结合中医“胃不和则卧不安”理论探讨睡眠障碍伴GERD的诊治思路。方法利用大规模全基因组关联研究汇总数据,选择相互独立且与GERD密切相关的遗传位点作为工具变量,通过逆方差加权法(IVW)、MR-Egger法、加权中位数法(WME)、简单众数法(SM)、加权众数法(WM)、MR多效性残差和与异质性法(MR-PRESSO)等MR方法,以OR值作为评价指标对GERD与睡眠障碍的因果关系进行探讨。结果IVW法结果显示,GERD可导致睡眠障碍发病风险升高44.3%(P=4.96×10^(-15),OR=1.443,95%CI:1.317~1.582);使用MR-Egger截距检测水平多效性,计算得P=0.646(P>0.05),提示结果不存在水平多效性;留一法(Leave-one-out sensitivity test)显示结果稳定,不存在对结果有强影响的IV。结论GERD是睡眠障碍发病的危险因素,与中医“胃不和则卧不安”理论相契合。Objective To explore the causal relationship between gastroesophageal reflux disease(GERD)and sleep disorder using Mendelian randomization(MR);To explore the diagnosis and treatment of sleep disorder with GERD by combining with the TCM theory that"gastric disharmony causing restless sleep".Methods Genetic loci independent of each other and closely related to GERD were taken as instrumental variables by pooling data from a large-scale genome-wide association study.The causal relationship between GERD and sleep disorder was explored with Mendelian randomization methods,such as Inverse Variance Weighted(IVW),MR Egger,Weighted Median(WME),Simple Mode(SM),Weighted Mode(WM)and MR Multiple Effectiveness Residual Sum and Heteroscedasticity(MR-PRESSO)using OR as an evaluation index.Results The results of the IVW method showed that GERD led to a 44.3%higher risk of developing sleep disorder(P=4.96×10^(-15),OR=1.443,95%CI:1.317-1.582);horizontal pleiotropy was detected using the MR-Egger intercept,which was calculated to be P=0.646(P>0.05),proving that there was no horizontal pleiotropy in the results;Leave-one-out sensitivity test showed that the results were stable and there were no instrumental variables that strongly influenced the results.Conclusion GRED is a risk factor for the development of sleep disorder,which is consistent with the TCM theory of"gastric disharmony causing restless sleep".

关 键 词：睡眠障碍 胃食管反流 孟德尔随机化 胃不和则卧不安 因果推断 

分 类 号：R259[医药卫生—中西医结合] R277.7[医药卫生—中医内科学]