饮食因素与冠心病的因果关系:一项单变量和多变量孟德尔随机化分析OA

Objective To analyze the causal relationship between dietary factors and coronary heart disease(CHD)by univariate and multivariate Mendelian randomization(MR)analysis.Methods All genome-wide association studies(GWAS)summary data in this study were obtained from the IEU open GWAS database.Firstly,univariate MR analysis was used to explore the causal relationship between 29 dietary factors and CHD,and dietary factors were exposure factors and CHD was the outcome.The main method for univariate MR analysis was inverse variance weighted(IVW),and MR-Egger regression and weighted median(WM)were auxiliary methods.Then,sensitivity analysis was used to confirm the reliability of the MR results.Finally,multivariate MR analysis was used to assess whether the impact of a dietary factor on CHD was independent of type 2 diabetes and daily smoking amount.Results The IVW analysis results showed that among the 29 dietary factors,only increased fresh fruit intake and cheese intake were protective factors for CHD,while increased poultry intake,tofu intake,and sugary food/beverage intake were risk factors for CHD(P<0.05);the WM analysis results showed that among the 29 dietary factors,only increased cheese intake was a protective factor for CHD,while increased poultry intake was a risk factor for CHD(P<0.05).The results of Cochran's Q test showed that there was significant heterogeneity between single nucleotide polymorphisms(SNPs)of cheese intake and sugary food/beverage intake(P<0.05),so the IVW fixed effect model was used for MR analysis;there was no significant heterogeneity among SNPs of fresh fruit intake,poultry intake and tofu intake(P>0.05),so IVW fixed effect model was used for MR analysis.The Mendelian randomization pleiotropy residual sum and outlier(MR-PRESSO)analysis results showed that outliers were only found in SNPs of fresh fruit intake,with rs4302893.The MR-Egger regression analysis results showed that there was no horizontal pleiotropy in the relationship between fresh fruit intake,poultry intake,cheese intake,tofu intake,and sugary food/beverage intake and CHD(P>0.05).The leave-one-out analysis results showed that there was no significant change in MR results after sequentially removing individual SNPs.Multivariate MR analysis showed that after controlling for type 2 diabetes and daily smoking amount,there was no causal relationship between the intake of fresh fruit,poultry,tofu,and sugary food/drink and CHD(P>0.05);however,increased cheese intake still was a protective factor for CHD(P<0.05).Conclusion Increased cheese intake is a protective factor for CHD,and increasing cheese intake appropriately may reduce the risk of CHD.No causal relationship was found between other dietary factors and CHD.