两样本双向孟德尔随机化分析胃食管反流病与偏头痛间的因果效应  

Two-sample bidirectional Mendelian randomization for analyzing the causal effect between gastroesophageal reflux disease and migraine headaches

作　　者：马佳昕 周元植 陈雯雯 赵雅涵 张旭 李雅睿[1,2] 和水祥 赵艳[1,2] ZHANG Xu;LI Yarui;HE Shuixiang;ZHAO Yan(Department of Gastroenterology,The First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061;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：《西安交通大学学报（医学版）》2024年第2期262-270,共9页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：国家自然科学基金资助项目(No.82303169,No.81900489);陕西省自然科学基础研究计划资助(No.2022JM-456)。

摘　　要：目的利用两样本双向孟德尔随机化(MR)研究方法,探讨胃食管反流病与偏头痛之间发病的因果关联,为两种疾病发病风险关联提供遗传学证据支持。方法从公开发表的全基因组关联分析(GWAS)数据库中获取两样本的单核苷酸多态性(SNP)信息,筛选出合适的SNP作为工具变量,利用逆方差加权法(IVW)、加权中位数法(WM)、MR-Egger回归法、加权众数法以及简单模型法五种MR分析方法进行双向MR分析,并进行敏感性检验。结果IVW显示以胃食管反流病为暴露的正向MR分析结果有阳性意义[OR=1.3987,95%CI(1.1817~1.6556),P=9.59×10^(-5)],以偏头痛为暴露的反向MR分析结果无阳性意义(P>0.05),在除MR-Egger外的其他方法中得到相同的结论。正向MR(P=0.92)与反向MR(P=0.64)均未发现工具变量具有水平多效性,留一法剔除单个SNP后结果具有稳健性。结论胃食管反流病与偏头痛之间可能存在单向的因果关联,胃食管反流病是偏头痛发病的危险因素。Objective To explore the causal association between the onset of gastroesophageal reflux disease(GERD) and migraine and to provide genetic evidence,a two-sample bidirectional Mendelian randomization(MR) method was used in this study.Methods Single nucleotide polymorphism(SNP) information for both samples was obtained from publicly available genome-wide association study(GWAS) databases,in which the appropriate SNPs were selected as instrumental variables,and then bidirectional MR analysis used five MR analysis methods including inverse variance weighting(IVW),MR-Egger regression,weighted median,weighted mode and simple mode methods,followed by sensitivity analysis.Results IVW showed positive results of forward MR analysis with GERD as exposure [OR=1.398 7,95%CI(1.181 7-1.655 6),P=9.59×10^(-5)],while no positive significance of reverse MR analysis results with migraine as exposure(P>0.05).The same results were obtained in methods other than MR-Egger method.Meanwhile,none of the instrumental variables were found to be horizontally polytomous(P=0.92,P=0.64),and the results were robust after the leave-one-out method to exclude single SNPs.ConclusionThere may be a unidirectional causal association between GERD and migraine,and GERD is a risk factor for migraine development.

关 键 词：胃食管反流病 偏头痛 孟德尔随机化 因果关系 危险因素 

分 类 号：R57[医药卫生—消化系统] R747.2[医药卫生—内科学]