摘要
目的 探讨椎管狭窄(spinal stenosis,SS)与便秘之间的全局、局部遗传相关性及双向因果关系。方法 利用来自欧洲人群的公开全基因组关联研究数据,采用全局和局部遗传相关性分析明确全局和局部遗传相关性,并进行双样本孟德尔随机化分析(two-sample Mendelian randomization,TSMR):使用逆方差加权法、MR-Egger回归法、加权中位数法及加权模式4种不同方法进行分析并评估结果;运用Cochra’sQ检验、留一法、MR-Egger截距测试、孟德尔随机多效性残差和异常值检验结果的稳定性和可靠性。结果 全局及局部基因遗传分析结果得出共71个区域存在至少一对性状具有局部遗传相关性。TSMR分析以SS为暴露,便秘为结局,基于逆方差加权法的结果提示二者有因果关系(OR=1.077,95%CI:1.034~1.122,P=0.000);Cochran’s Q检验、MR-Egge截距检测表明不存在异质性或多效性,通过孟德尔随机多效性残差和异常值分析进行验证表明本研究结果不存在异常值;利用留一法敏感度分析显示研究结果稳定。以便秘为暴露因素,SS为结果,未找到符合条件的工具变量。结论 SS与便秘之间存在显著的全局及局部遗传相关性,SS可能是便秘发生的危险因素。
Objective To explore the global and loci-specific genetic correlations and bidirectional causal relationships between spinal stenosis(SS)and constipation.Methods Utilizing the publicly available genome-wide association study data from the European population,linkage disequilibrium score regression and local analysis of variant association were used for quantifying genetic correlation at both global(genome-wide)and local(genomic regions)levels,and a two-sample Mendelian randomization(TSMR)analysis was conducted:Four distinct methods,namely the inverse variance weighting method,MR-Egger regression method,weighted median method,and weighted mode,were utilized for analysis and evaluation of the results;Cochran’s Q test,leave-one-out method,MR-Egger intercept test,Mendelian randomization polymorphic residuals,and outlier tests were applied to examine the stability and reliability of the results.Results The analysis of linkage disequilibrium score regression and local analysis of variant association revealed that a total of 71 regions had at least one pair of traits with local genetic correlations.The TSMR analysis,with SS as the exposure and constipation as the outcome,based on the results of the inverse variance weighting method,suggested a causal relationship between two(OR=1.077,95%CI:1.034-1.122,P=0.000);Cochran’s Q test and MR-Egger intercept test indicated the absence of heterogeneity or pleiotropy,and were verified by the analysis of Mendelian randomization polymorphic residuals,and outlier tests,demonstrating that the results of this study did not exhibit horizontal pleiotropy;The sensitivity analysis using the leave-one-out method indicated that the research results were stable.With constipation as the exposure factor and SS as the outcome,no eligible instrumental variables were found.Conclusion There are significant global and loci-specific genetic correlations between SS and constipation,and SS may be a risk factor for the occurrence of constipation.
作者
郭立鹏
胡炎芝
周明瀚
徐无忌
GUO Lipeng;HU Yanzhi;ZHOU Minghan;XU Wuji(The Second Clinical College of Traditional Chinese Medicine,Hunan University of Traditional Chinese Medicine,Changsha 410005,Hunan,China;Department of OrthopedicsⅡ,the Second Affiliated Hospital of Hunan University of Traditional Chinese Medicine,Changsha 410005,Hunan,China)
出处
《中国现代医生》
2025年第6期45-49,共5页
China Modern Doctor
关键词
椎管狭窄
便秘
全局遗传相关性分析
局部遗传相关性分析
双样本孟德尔随机化分析
Spinal stenosis
Constipation
Linkage disequilibrium score regression
Local analysis of variant association
Two-sample Mendelian randomization
