摘要
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.
作者
冉清智
李傲霜
马静卓
陈恒文
张跃
RAN Qingzhi;LI Aoshuang;MA Jingzhuo;CHEN Hengwen;ZHANG Yue(Guang′anmen Hospital,China Academy of Chinese Medical Sciences,Beijing 100053,China;Dongzhimen Hospital,BeijingUniversity of Chinese Medicine,Beijing 100070,China)
出处
《中西医结合心脑血管病杂志》
2024年第21期3841-3849,共9页
Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease
基金
国家自然科学基金项目(No.82074396)
中国中医科学院科技创新工程重大攻关项目(No.CI2021A05011)
中国中医科学院科技创新工程创新团队项目(No.CI2021B017-05)
中国中医科学院广安门医院续航人才工程青年拔尖人才培养项目
新疆维吾尔自治区区域协同创新专项(上海合作组织科技伙伴计划及国际科技合作计划)项目“民族药海外注册与临床国际科技合作与服务研究”(No.2022E01001)。
关键词
冠心病
孟德尔随机化
维生素D
因果关系
coronary heart disease
mendelian randomization
vitamin D
causality
