基于双样本孟德尔随机化分析微量营养素水平与幻肢痛之间的因果关系  

Exploring the causality between micronutrients and phantom limb pain based on two-sample Mendelian randomization analysis

作　　者：杨理 李文辉 郑涵 张亮[1] 王凯[1] Yang Li;Li Wenhui;Zheng Han;Zhang Liang;Wang Kai(Department of Orthopedics,The Second Hospital of Tianjin Medical University,Tianjin City 30021l,China)

机构地区：[1]天津医科大学第二医院骨科,天津市300211

出　　处：《中华疼痛学杂志》2024年第5期700-708,共9页Chinese Journal Of Painology

基　　金：天津市教委科研计划(2023KJ024)。

摘　　要：目的:运用双样本孟德尔随机化(TSMR)探究微量营养素水平与幻肢痛(PLP)之间的因果关系。方法:从公开FinnGen数据库获取PLP的全基因组关联研究(GWAS)数据,从PubMed及IEU OpenGWAS开放数据库中收集并筛选15种微量营养素的GWAS数据,通过设定阈值参数筛选工具变量(IVs)。TSMR分析采用逆方差加权(IVW)、MR-Egger回归、加权中位数(WME)、简单模式(SM)和加权模式(WM)。Cochran's Q检验及MR-Egger回归的截距项分别用于评估各IVs间的统计学异质性及水平多效性。结果:研究最终纳入169个与PLP及微量营养素密切相关的IVs。IVW结果表明,基因预测的镁(OR=0.014,95%CI:0.0003~0.571,P=0.024)与PLP存在负向因果关系;而铜(OR=1.226,95%CI:0.782~1.923,P=0.375)、钾(OR=1.729,95%CI:0.052~57.968,P=0.760)、维生素B 12(OR=21.444,95%CI:0.473~973.010,P=0.115)、维生素B 6(OR=1.763,95%CI:0.091~34.220,P=0.708)、钙(OR=0.533,95%CI:0.030~9.388,P=0.667)、胡萝卜素(OR=0.240,95%CI:0.011~5.084,P=0.360)、叶酸(OR=0.140,95%CI:0.005~3.786,P=0.243)、铁(OR=0.126,95%CI:0.003~4.973,P=0.269)、硒(OR=0.869,95%CI:0.406~1.863,P=0.718)、锌(OR=0.923,95%CI:0.435~1.957,P=0.834)、维生素A(OR=0.003,95%CI:0.000~0.000,P=0.871)、维生素C(OR=0.714,95%CI:0.010~53.056,P=0.878)、维生素D(OR=0.121,95%CI:0.004~3.558,P=0.221)和维生素E(OR=0.246,95%CI:0.011~5.348,P=0.372)与PLP无明显因果关系。Cochran's Q检验和MR-Egger回归的截距项表明各IVs不存在统计学异质性及水平多效性(P>0.05)。结论:较高的微量营养素镁水平可能会降低幻肢痛的发病风险。Objective To investigate the causality between micronutrients and phantom limb pain(PLP)using two-sample Mendelian randomization(TSMR).Methods Pooled genome-wide association studies(GWAS)data of PLP was derived from the FinnGen database,while pooled GWAS data of 15 micronutrients was collected and screened from PubMed and IEU OpenGWAS databases.Instrumental variables(IVs)were extracted according to prespecified threshold.TSMR analysis was performed through inverse variance weighted(IVW),Mendelian randomization egger regression(MR-Egger),weighted median(WME),simple mode(SM),and weighted mode(WM).Cochran's Q test was used to analyze the heterogeneity of IVs,and the intercept of MR-Egger was used to evaluate the horizontal pleiotropy of IVs.Results A total of 169 IVs closely related to micronutrients and PLP were screened out.The IVW analysis results showed significant negative correlation between magnesium(OR=0.014,95%CI:0.0003-0.571,P=0.024)and PLP,but no significant correlation between copper(OR=1.226,95%CI:0.782-1.923,P=0.375),potassium(OR=1.729,95%CI:0.052-57.968,P=0.760),vitamin B 12(OR=21.444,95%CI:0.473-973.010,P=0.115),vitamin B 6(OR=1.763,95%CI:0.091-34.220,P=0.708),calcium(OR=0.533,95%CI:0.030-9.388,P=0.667),carotene(OR=0.240,95%CI:0.011-5.084,P=0.360),folate(OR=0.140,95%CI:0.005-3.786,P=0.243),iron(OR=0.126,95%CI:0.003-4.973,P=0.269),selenium(OR=0.869,95%CI:0.406-1.863,P=0.718),zinc(OR=0.923,95%CI:0.435-1.957,P=0.834),vitamin A(OR=0.003,95%CI:0.000-0.000,P=0.871),vitamin C(OR=0.714,95%CI:0.010-53.056,P=0.878),vitamin D(OR=0.121,95%CI:0.004-3.558,P=0.221),vitamin E(OR=0.246,95%CI:0.011-5.348,P=0.372)and PLP respectively.Cochran's Q test and the intercept of MR-Egger showed no heterogeneity or horizontal pleiotropy of IVs(P>0.05).Conclusion Higher levels of micronutrient magnesium may reduce the risk of phantom limb pain.

关 键 词：孟德尔随机化分析 幻肢痛 微量营养素 

分 类 号：R15[医药卫生—营养与食品卫生学]