骨质疏松和骨密度与胃食管反流病的孟德尔随机化研究  

Mendelian randomization study about osteoporosis and bone mineral density on gastroesophageal reflux disease

作　　者：陈雯雯 周元植 张旭 马佳昕 赵雅涵 李雅睿[1,2] 赵艳 和水祥[1,2] 任牡丹 CHEN Wenwen;ZHOU Yuanzhi;ZHANG Xu;MA Jiaxin;ZHAO Yahan;LI Yarui;ZHAO Yan;HE Shuixiang;REN Mudan(Department of Gastroenterology,the First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061,China;Clinical Medical Research Center for Digestive Diseases of Shaanxi Province(Oncology),Xi’an 710061,China)

机构地区：[1]西安交通大学第一附属医院消化内科,陕西西安710061 [2]陕西省消化系统疾病(肿瘤方向)临床医学研究中心,陕西西安710061

出　　处：《中国骨质疏松杂志》2024年第8期1108-1115,共8页Chinese Journal of Osteoporosis

基　　金：陕西省自然科学基础研究计划(2022JM-456);国家自然科学基金(81900489,82303169)。

摘　　要：目的用两样本孟德尔随机化法评估骨质疏松与骨密度和胃食管反流病(gastroesophageal reflux disease,GERD)的因果关系。方法暴露包括骨质疏松、全身骨密度、腰椎骨密度、股骨颈骨密度、足跟骨密度、前臂骨密度,结局为GERD。筛选与暴露强相关的单核苷酸多态性位点为工具变量进行两样本孟德尔随机化(MR)分析。采用逆方差加权(IVW)法作为主要方法,加权中位数法、MR-Egger法作为补充,评估暴露与结局的因果关系。敏感性分析验证结果的稳定性与可靠性。结果IVW法表明遗传预测的骨质疏松是GERD的危险因素(P=0.005,OR=35.687,95%CI:3.009~423.194),全身骨密度(P=1.57×10-5,OR=0.910,95%CI:0.872~0.950)和腰椎骨密度(P=0.005,OR=0.917,95%CI:0.863~0.974)的增加是GERD的保护因素,而股骨颈骨密度、前臂骨密度、足跟骨密度与GERD不存在因果关系。异质性检验表明足跟骨密度与GERD之间存在异质性,但不影响随机效应IVW法得出的因果关系的结论,其余暴露与GERD不存在异质性。MR-Egger-intercept表明无水平多效性。留一法表明分析结果稳健。结论骨质疏松是GERD的危险因素,全身骨密度和腰椎骨密度的增加是GERD的保护因素。这提示骨质疏松症患者应进行GERD的早期筛查及诊治,本研究为临床医生提供了新的诊疗思路。Objective To evaluate the causal relationship between osteoporosis and bone mineral density(BMD)on gastroesophageal reflux disease(GERD)through two-sample mendelian randomization analysis.Methods The exposure factors include osteoporosis,total body BMD,lumbar spine BMD,femoral neck BMD,heel BMD,and forearm BMD.The outcome factor is GERD.The single nucleotide polymorphisms(SNPs)associated with exposure factors were screened as instrumental variables for two-sample Mendelian randomization analysis.The inverse variance-weighted(IVW)method was used as main method to assess causal relationship between exposure and outcome factors,meanwhile weighted median and MR-Egger regression were supplemented.The stability and reliability of the result were verified by several sensitivity analysis method.Results The inverse variance-weighted analysis indicated that osteoporosis was a risk factor for GERD(P=0.005,OR=35.687,95%CI:3.009-423.194),increased total body BMD(P=1.57×10-5,OR=0.910,95%CI:0.872-0.950)and increased lumbar spine BMD(P=0.005,OR=0.917,95%CI:0.863-0.974)were protective factors for GERD.However,there was no causal relationship between femoral neck BMD,heel BMD,and forearm BMD and GERD.Heterogeneity was found between heel BMD and GERD,but the casual relationship through random effects IVW method was not be influenced.Heterogeneity was not demonstrated between GERD and other exposure factors.No pleiotropy was found by using MR-Egger-intercept.The"leave one out method"analysis showed that the MR analysis result were robust.Conclusion Osteoporosis is a risk factor for GERD,while increased total body bone density and increased lumbar bone density are protective factors for GERD.This implied that osteoporosis patients should screen GERD earlier for further diagnosis and treatment,which provide a new diagnosis and treatment idea for clinicians.

关 键 词：骨质疏松 骨密度 胃食管反流病 孟德尔随机化 

分 类 号：R571[医药卫生—消化系统] R589[医药卫生—内科学]