摘要
目的:通过两样本、多变量、双向孟德尔随机化(MR)研究探讨血清微量营养素(维生素A、维生素B6、维生素B9、维生素B12、维生素C、维生素D、维生素E、铜、铁、硒、锌、钙、镁、钾)与冠状动脉粥样硬化之间的因果关系。方法:使用公开的欧洲人群全基因组关联研究汇总数据,以上述14种血清微量营养素为暴露因素,单核苷酸多态性(SNP)为工具变量,冠状动脉粥样硬化为结局。用逆方差加权法(IVW)、MR-Egger回归法、加权中位数法(WME)、简单模型、加权模型进行两样本MR分析,评估各血清微量营养素与冠状动脉粥样硬化之间的关系。采用多变量MR分析评价单一暴露因素对冠状动脉粥样硬化的独立效应,采用反向MR分析评价它们是否存在反向因果关系。使用Cochran's Q检验、MR-Egger回归法、MR-PRESSO以及留一法进行敏感性分析,以评价结果稳健性。结果:单变量两样本MR分析发现,血清维生素A(IVW:OR=0.019,95%CI:0.001~0.451,P=0.014)、维生素B12(IVW:OR=1.221,95%CI:1.015~1.469,P=0.034)、铜(IVW:OR=1.023,95%CI:1.003~1.044,P=0.026)和钾(IVW:OR=0.837,95%CI:0.714~0.980,P=0.027)水平与冠状动脉粥样硬化风险之间存在显著关联。多变量MR分析显示,血清维生素A(IVW:OR=0.016,95%CI:0.001~0.214,P=0.002)和铜(IVW:OR=1.029,95%CI:1.002~1.056,P=0.036)水平对冠状动脉粥样硬化存在独立因果效应。反向MR分析观察到,冠状动脉粥样硬化风险与血清维生素A水平之间存在反向因果关系,但效应极小(IVW:OR=0.999),冠状动脉粥样硬化风险与血清铜水平之间无反向因果关联。几乎没有证据支持其余血清微量营养素与冠状动脉粥样硬化风险之间存在因果关系。敏感性分析显示,上述结果稳健。结论:血清维生素A和铜水平可能对冠状动脉粥样硬化易感性有重要作用。
Objectives:A two-sample,multivariable,bidirectional Mendelian randomization(MR)analysis was conducted to explore the causal relationships between serum micronutrients(including vitamin A,vitamin B6,vitamin B9,vitamin B12,vitamin C,vitamin D,vitamin E,copper,iron,selenium,zinc,calcium,magnesium,and potassium)and coronary atherosclerosis(CA).Methods:Publicly available data from genome-wide association studies in European populations were analyzed,14 serum micronutrients were used as exposure factors and single nucleotide polymorphisms(SNPs)were used as instrumental variables,outcome was defined as CA.A two-sample MR analysis was performed using inverse variance weighted(IVW)method,MR-Egger regression,weighted median estimator(WME),simple model,and weighted model to assess the relationship between each micronutrient and CA.Multivariable MR analysis was used to evaluate the independent impacts of single exposure factors on CA,reverse MR was applied to assess the potential for reverse causality.Sensitivity analysis was conducted using Cochran's Q test,MR-Egger regression,MR-PRESSO,and leave-one-out analysis to evaluate the robustness of the results.Results:The univariable two-sample MR study evidenced the significant associations between serum levels of vitamin A(IVW:OR=0.019,95%CI:0.001-0.451,P=0.014),vitamin B12(IVW:OR=1.221,95%CI:1.015-1.469,P=0.034),copper(IVW:OR=1.023,95%CI:1.003-1.044,P=0.026),and potassium(IVW:OR=0.837,95%CI:0.714-0.980,P=0.027)with the risk of CA.After adjustment using multivariable MR analysis,independent causal effects on CA were observed for serum levels of vitamin A(IVW:OR=0.016,95%CI:0.001-0.214,P=0.002)and copper(IVW:OR=1.029,95%CI:1.002-1.056,P=0.036).Reverse MR analysis observed a reverse causal relationship between CA risk and serum vitamin A level,though the effect was minimal(IVW:OR=0.999),while no reverse causality was found between CA risk and serum copper level.There was no evidence to support a causal relationship between the remaining serum micronutrients and CA.These findings were robust through extensive sensitivity analyses.Conclusions:The levels of serum vitamin A and copper may relate to the susceptibility of CA in the studied population.
作者
刘畅
谢骞
张兴
张重阳
冀伟
房彬彬
刘芬
杨毅宁
李晓梅
LIU Chang;XIE Qian;ZHANG Xing;ZHANG Chongyang;JI Wei;FANG Binbin;LIU Fen;YANG Yining;LI Xiaomei(Department of Cardiology,First Affiliated Hospital of Xinjiang Medical University,Urumqi 830054,China;Department of Cardiology,People's Hospital of Xinjiang Uygur Autonomous Region,Urumqi 830001,China)
出处
《中国循环杂志》
CSCD
北大核心
2024年第12期1183-1189,共7页
Chinese Circulation Journal
基金
新疆维吾尔自治区重点研发计划(2022B03022-2)
国家自然科学基金(8216020109)
中央引导地方科技发展专项资金(ZYYD2022C21)
新疆维吾尔自治区“天山英才”培养计划(2023TSYCLJ0035)。
