首页|维生素D与冠心病因果关系的双向两样本孟德尔随机化研究

维生素D与冠心病因果关系的双向两样本孟德尔随机化研究

A Two-way Two-sample Mendelian Randomization Study of the Causal Relationship Between Vitamin D and Coronary Heart Disease

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目的:探索维生素D与冠心病(CHD)的因果关系.方法:从一些广泛的全基因组关联研究(GWAS)中收集维生素D与CHD强相关的独立单核苷酸多态性位点(SNP)作为工具变量.孟德尔随机化估计采用逆方差加权法(IVW)、加权中位数法和MR-Egger法.敏感性分析使用Cochran's Q检验、MR-Egger截距检验、MR-PRESSO、MR Steiger检验、leave-one-out分析和漏斗图.结果:共筛选到69个维生素D的SNP,IVW分析法显示维生素D和CHD之间存在因果关系[OR=0.994,95%CI(0.988,0.999),P=0.0476],Cochran's Q显示Q=179.7898,P=1.76e-12,表明纳入分析的SNP之间不存在异质性,MR-Egger截距P=0.7461144,表明筛选得到的SNP不存在基因多效性,MR-PRESSO未发现离群的SNP,leave-one-out敏感性分析显示因果估计不会受到某些SNP效应的影响.反向孟德尔随机化分析结果IVW分析法OR=0.416,95%CI(0.064,2.688),P=0.35705610,Cochran's Q显示Q=66.90252,P=1.022131e-13,MR-Egger截距P=0.850615,表明维生素D和CHD不支持反向因果关系.结论:通过孟德尔随机化研究证明维生素D对CHD存在因果关联,但是反向因果关系是不可靠的,有助于提高对维生素D保护CHD机制的理解.
Objective:To explore the causal relationship between vitamin D and coronary heart disease(CHD).Methods:Independent single nucleotide polymorphism(snp) loci strongly associated with vitamin D and CHD were collected from a number of extensive genome-wide association studies(GWAS) as instrumental variables.The inverse variance weighting(IVW),weighted median and MR-Egger method were used to estimate Mendelian randomization.Cochran's Q test,MR-Egger intercept test,MR-PRESSO test,MR Steiger test,leave-one-out analysis,and funnel plot were used for sensitivity analysis.Results:A total of 69 SNPS of vitamin D were screened.IVW analysis showed a causal relationship between vitamin D and CHD(OR=0.994,95%CI 0.988-0.999,P=0.0476).Cochran's Q showed Q=179.7898,P=1.76e-12,indicating that there was no heterogeneity among the SNP in the analysis.The MR-Egger intercept was P=0.7461144,indicating that there was no genetic pleiotropy in the SNP obtained from the screening.MR-PRESSO did not find any outlier SNP.Leave-one-out sensitivity analysis showed that causal estimation would not be affected by the effect of certain SNP.Reverse Mendelian randomization analysis IVW analysis,OR=0.416,95%CI(0.064-2.688),P=0.35705610,Cochran's Q shows Q=66.90252,P=1.022131e-13,and MR-Egger intercept (P=0.85615),indicated that vitamin D and CHD did not support reverse causality.Conclusion:This Mendelian randomization study demonstrates some causal association between vitamin D and CHD,but reverse causality is unreliable and to helpful to understanding some the mechanisms that vitamin D protects CHD.

coronary heart diseasemendelian randomizationvitamin Dcausality

冉清智、李傲霜、马静卓、陈恒文、张跃

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中国中医科学院广安门医院 北京 100053

北京中医药大学东直门医院 北京 100070

冠心病 孟德尔随机化 维生素D 因果关系

2024

中西医结合心脑血管病杂志
中国中西医结合学会 山西医科大学第一医院

中西医结合心脑血管病杂志

CSTPCD
影响因子:1.463
ISSN:1672-1349
年,卷(期):2024.22(21)