Causal Relationship Between Serum Micronutrients and Coronary Atherosclerosis:a Two-sample Multivariable Bidirectional Mendelian Randomization Study
10.3969/j.issn.1000-3614.2024.12.005
- VernacularTitle:血清微量营养素与冠状动脉粥样硬化因果关系的两样本、多变量、双向孟德尔随机化研究
- Author:
Chang LIU
1
;
Qian XIE
;
Xing ZHANG
;
Chongyang ZHANG
;
Wei JI
;
Binbin FANG
;
Fen LIU
;
Yining YANG
;
Xiaomei LI
Author Information
1. 新疆医科大学第一附属医院 心脏中心,乌鲁木齐 830054
- Publication Type:Journal Article
- Keywords:
coronary atherosclerosis;
micronutrients;
vitamin A;
copper;
Mendelian randomization
- From:
Chinese Circulation Journal
2024;39(12):1183-1189
- CountryChina
- Language:Chinese
-
Abstract:
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.
