基于双样本孟德尔随机化分析1400种血浆代谢产物和COVID-19的因果关系
Causal associations between 1400 plasma metabolites and COVID-19 based on two-sample Mende-lian randomization
陈鹏程 1郭雅琪 2赵筱琳 2管庆波3
作者信息
- 1. 山东大学,山东省立医院内分泌代谢病科,山东济南 250021
- 2. 内分泌糖脂代谢与脑老化教育部重点实验室;山东第一医科大学附属省立医院内分泌代谢病科,山东济南 250021;山东省糖尿病与代谢疾病临床医学研究中心,山东济南 250021;山东省内分泌与代谢病研究所,山东济南 250021
- 3. 山东大学,山东省立医院内分泌代谢病科,山东济南 250021;内分泌糖脂代谢与脑老化教育部重点实验室;山东第一医科大学附属省立医院内分泌代谢病科,山东济南 250021;山东省糖尿病与代谢疾病临床医学研究中心,山东济南 250021;山东省内分泌与代谢病研究所,山东济南 250021
- 折叠
摘要
目的 探讨1 400种血浆代谢产物和2019冠状病毒病(COVID-19)的严重程度、住院率和易感性之间的潜在因果关系,以寻找COVID-19和长新冠综合征治疗和干预的潜在靶点.方法 采用双样本孟德尔随机化(MR)方法,以1 400种血浆代谢产物为暴露因素,COVID-19严重程度、住院率和易感性为结局因素.采用逆方差加权法(IVW)、约束最大似然与模型平均法(cML-MA)、MR-Egger回归法和加权中位数法来研究暴露因素和结局因素之间的因果关系.敏感性分析包括异质性分析、多效性分析,以检验MR分析结果的稳健性.结果 血浆中较高水平的花生四烯酸(20:4n6)(IVW:OR=0.899,95%CI:0.853～0.947,P=6.916E-05;cML-MA:OR=0.891,95%CI:0.849～0.937,P=5.022E-06)和色氨酸甜菜碱(IVW:OR=0.909,95%CI:0.856～0.965,P=0.002;cML-MA:OR=0.887,95%CI:0.839～0.938,P=2.629E-05)与较低的COVID-19严重程度相关;色氨酸甜菜碱(IVW:OR=0.940,95%CI:0.897～0.986,P=0.011;cML-MA:OR=0.917,95%CI:0.883～0.952,P=5.700E-06)水平升高与COVID-19住院率降低相关;色氨酸甜菜碱(IVW:OR=0.966,95%CI:0.949～0.983,P=0.000 1;cML-MA:OR=0.960,95%CI:0.945～0.976,P= 1.210E-06)水平升高与COVID-19易感性降低相关.结论 色氨酸甜菜碱可以降低COVID-19严重程度、住院率和易感性,花生四烯酸(20:4n6)可以降低COVID-19的严重程度.
Abstract
Objective To investigate the potential causal associations between 1 400 plasma metabolites and the se-verity,hospitalization and susceptibility of Coronavirus disease 2019(COVID-19).To detect potential targets for the treat-ment and intervention of COVID-19 and long COVID.Methods The study performed a two-sample Mendelian random-ization(MR)method with 1 400 plasma metabolites as the exposure and the severity,hospitalization,and susceptibility of COVID-19 as the outcomes.The inverse-variance weighted(IVW)method,the constrained maximum likelihood and mod-el averaging(cML-MA)method,the MR-Egger method and the weighted median method were employed to explore the causal relationship between 1 400 plasma metabolites and COVID-19.Sensitivity analysis included heterogeneity and plei-otropy analysis to assess the robustness of MR analysis results.Results Elevated levels of arachidonate(20:4n6)(IVW:OR=0.899,95%CI:0.853-0.947,P=6.916E-05;cML-MA:OR=0.891,95%CI:0.849-0.937,P=5.022E-06)and tryptophan betaine(IVW:OR=0.909,95%CI:0.856-0.965,P=0.002;cML-MA:OR=0.887,95%CI:0.839-0.938,P=2.629E-05)in plasma were associated with lower severity of COVID-19;Elevated levels of tryptophan betaine(IVW:OR=0.940,95%CI:0.897-0.986,P=0.011;cML-MA:OR=0.917,95%CI:0.883-0.952,P=5.700E-06)were associat-ed with lower hospitalization of COVID-19;Elevated levels of tryptophan betaine(IVW:OR=0.966,95%CI:0.949-0.983,P=0.000 1;cML-MA:OR=0.960,95%CI:0.945-0.976,P=1.210E-06)were associated with lower susceptibility of COVID-19.Conclusions It is concluded that high concentrations of tryptophan betaine could reduce the severity,hospitalization,and susceptibility of COVID-19.Additionally,high concentrations of arachidonate(20:4n6)can reduce the severity of COVID-19.
关键词
血浆代谢产物/色氨酸甜菜碱/花生四烯酸(20:4n6)/COVID-19/长新冠/孟德尔随机化Key words
plasma metabolites/tryptophan betaine/arachidonate(20:4n6)/COVID-19/long COVID/Mende-lian randomization引用本文复制引用
出版年
2024
NETL
NSTL
维普
万方数据