Causal Relationship Between Serum Micronutrients and Coronary Atherosclerosis:a Two-sample Multivariable Bidirectional Mendelian Randomization Study
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.
万方数据
维普
