神经质人格与功能性胃肠道疾病的因果关系:一项孟德尔随机化研究  

Causal relationship between neuroticism and functional gastrointestinal disorders:a Mendelian randomized study

作　　者：惠馨 郑亚 王玉平[2,3] 周永宁[2,3] 郭庆红[2,3] HUI xin;ZHENG Ya;WANG Yuping;ZHOU Yongning;GUO Qinghong(The First Clinical Medical College,Lanzhou University,Lanzhou 730000,P.R.China;Department of Gastroenterology,The First Hospital of Lanzhou University,Lanzhou 730000,P.R.China;Gansu Province Clinical Research Center for Digestive Diseases,Lanzhou 730000,P.R.China)

机构地区：[1]兰州大学第一临床医学院,兰州730000 [2]兰州大学第一医院消化科,兰州730000 [3]兰州大学第一医院,甘肃省消化系疾病临床医学研究中心,兰州730000

出　　处：《中国循证医学杂志》2025年第2期155-161,共7页Chinese Journal of Evidence-based Medicine

基　　金：甘肃省联合科研基金重大项目(编号:23JRRA1487);甘肃省卫生健康行业科研项目(编号:GSWSQN2023-02)。

摘　　要：目的采用孟德尔随机化方法(MR)探讨神经质人格与功能性胃肠病之间的关系。方法基于神经质人格和2种功能性胃肠病,即功能性消化不良(FD)、肠易激综合征(IBS)的全基因组关联研究数据,提取适当的单核苷酸多态性(SNP)作为工具变量,采用逆方差加权法(IVW)作为主要的分析方法,并通过Cochran’s Q检验、MR-PRESSO检验、MR-Egger截距、留一法进行敏感性分析。进一步进行两步法MR分析,以检查咖啡摄入、饮酒、吸烟、抑郁的中介效应。结果单因素MR分析显示,遗传决定的神经质人格会增加FD和IBS的发病风险[FD:OR=1.448,95%CI(1.057,1.983),P=0.021;IBS:OR=1.705,95%CI(1.210,2.403),P=0.002]。Cochran’s Q检验、MR-Egger截距、MR-PRESSO未观察到显著的异质性或水平多效性。留一法分析也未发现单个SNP对整体结果有较大的影响。多因素MR分析表明,即使在调整其他混杂因素后,神经质人格与FD及IBS患病风险升高之间的关联仍然存在。两步法MR中介分析揭示,抑郁在这一效应中起到部分中介作用,中介比例分别为59.41%[95%CI(5.69%,113.12%)]和67.53%[95%CI(31.55%,103.51%)]。结论神经质人格与FD及IBS之间存在一定程度的因果关联,而抑郁可能在这种关联中扮演着重要的中介角色。Objective To investigate the relationship between neuroticism and functional gastrointestinal disorders using Mendelian randomized(MR).Methods Based on the genome-wide association study data of neuroticism and 2 functional gastrointestinal disorders,i.e.,functional dyspepsia(FD),and irritable bowel syndrome(IBS),appropriate single nucleotide polymorphisms(SNP)were extracted as instrumental variables,and inverse variance weighted(IVW)was applied as the main analysis method,and sensitivity analyses were performed by Cochran’s Q test,MR-PRESSO test,MR-Egger intercept,and leave one out analysis.Further two-step MR analyses were performed to examine the mediating effects of coffee intake,alcohol consumption,smoking,depression.Results The univariable MR analysis showed that genetically determined neuroticism was positively causally associated with the risk of developing FD and IBS(FD:OR=1.448,95%CI 1.057 to 1.983,P=0.021;IBS:OR=1.705,95%CI 1.210 to 2.403,P=0.002).Cochran's Q-test,MR-Egger intercept,MR-PRESSO did not observe significant heterogeneity or horizontal pleiotropy.Leave-one-out analyses also did not find a large effect of individual SNPs on the overall results.Multivariable MR analyses showed that the association between neurotic personality and elevated risk of FD and IBS prevalence persisted even after adjusting for other confounders.Further two-step MR mediation analyses revealed that depression partially mediated this effect,with mediation proportions of 59.41%(95%CI 5.69%to 113.12%)and 67.53%(95%CI 31.55%to 103.51%),respectively.Conclusion There is a degree of causal association between neuroticism and FD and IBS,and depression may play an important mediating role in this association.

关 键 词：神经质人格 功能性胃肠病 孟德尔随机化分析 因果关系 中介分析 

分 类 号：R57[医药卫生—消化系统]