咖啡消费与动脉粥样硬化风险的孟德尔随机化研究

Mendelian randomization study on coffee consumption and atherosclerosis risk

[目的]研究咖啡消费与动脉粥样硬化风险之间的因果关系。[方法]利用公开基因组数据库IEU Open GWAS project网站获取相关数据,筛选与暴露和结局密切相关的工具变量,分别采用逆方差加权法、加权中位数和MR Egger法进行孟德尔随机化分析,以评估咖啡消费与动脉粥样硬化(包括冠状动脉粥样硬化、外周动脉粥样硬化、脑动脉粥样硬化和其他动脉粥样硬化)之间的因果关系,同时采用Egger intercept检测水平多效性,采用Cochran Q检验进行异质性评估,采用留一法检验敏感性,保证结果稳健性。[结果]研究纳入工具变量F值均大于10,不存在弱工具变量偏倚。咖啡消费与冠状动脉粥样硬化风险(OR=1.5355,95%CI:1.1084~2.1272,P=0.0099)、外周动脉粥样硬化(OR=2.0986,95%CI:1.1822~3.7257,P=0.0114)、其他动脉粥样硬化(OR=1.8645,95%CI:1.0529~3.3024,P=0.0326)呈显著正相关,与脑动脉粥样硬化风险无显著相关性。异质性检验Q_pval>0.05,水平多效性检验Intercept P>0.05。[结论]研究筛选的单核苷酸多态性均为强工具变量,未见异质性与水平多效性,结果可靠。本研究在基因层面表明,咖啡消费增加了冠状动脉、外周动脉以及其他动脉粥样硬化的风险,与脑动脉粥样硬化风险无显著相关性。动脉粥样硬化患者的健康管理应降低咖啡消费。

Aim To study the causal relationship between coffee consumption and atherosclerosis risk.Methods Based on the public genome database IEU Open GWAS project website,relevant data were obtained,and instrumental variables closely related to exposure and outcome were screened.Mendelian randomization analysis was performed using the inverse variance weighted method,weighted median method,and MR Egger method to assess the causal relationship between coffee consumption and arteriosclerosis(including coronary atherosclerosis,peripheral atherosclerosis,cerebral atherosclerosis,and other atherosclerosis).In addition,the Egger intercept method was used to detect the level of pleiotropy,the Cochran Q test was used to assess the heterogeneity,and the leave one out method was used to perform sensitivity analysis,so as to ensure the robustness of the results.Results The study showed that the F-values of the instrumental variables included in the study were all greater than 10,and there was no weak instrumental variables bias.Coffee consumption was positively correlated with the risk of coronary atherosclerosis(OR=1.5355,95%CI=1.1084~2.1272,P=0.0099),peripheral atherosclerosis(OR=2.0986,95%CI=1.1822~3.7257,P=0.0114),and other atherosclerosis(OR=1.8647,95%CI=1.0529~3.3024,P=0.0326),but not with the risk of cerebral atherosclerosis.Heterogeneity test Q_pval>0.05,level pleiotropy test interval P>0.05.Conclusions The single nucleotide polymorphisms selected in the study are all strong instrumental variables,and there is no heterogeneity or horizontal pleiotropy,indicating reliable results.The research shows that coffee consumption increases the risk of coronary atherosclerosis,peripheral atherosclerosis and other atherosclerosis,and has no significant correlation with the risk of cerebral atherosclerosis.The health management of atherosclerosis patients should reduce coffee consumption.