Causal effect of fresh and dried fruit intake on risk of coronary heart disease and myocardial infarction:a two sample Mendelian randomization study

ZHU Dong-jie; ZHU Xiu-long

doi:10.3969/j.issn.1672-5301.2025.11.011

Abstract：Objective To explore the causal relationship between the genetically predicted intake of fresh fruits and dried fruits and coronary heart disease using two-sample Mendelian randomization(MR).Methods Based on the genome-wide association study(GWAS)data from a European population,the single nucleotide polymorphisms(SNPs)associated with fresh fruit intake(n=433186)and dried fruit intake(n=409125)were selected as instrumental variables.The outcome data were from Finngen R12 database in Finland,including atherosclerosis(n=482913),coronary heart disease(n=500348)and myocardial infarction(n=447837).By setting a genome-wide significance threshold(P<5×10-8)and performing linkage disequilibrium(LD)exclusion(r2<0.001,distance>10000 kb),the independence and efficacy of IV were ensured.The main analysis method is inverse variance weighted(IVW),supplemented by sensitivity tests such as MR Egger regression,weighted median and weighted mode.In addition,Cochran Q test,MR Egger intercept test and MR-PRESSO analysis were conducted to evaluate the heterogeneity and horizontal pleiotropy.Results In the analysis of the fresh fruit intake,it was found that the fresh fruit intake was significantly negatively correlated with coronary heart disease(OR=0.63,95％CI 0.45-0.88,P=0.007)and myocardial infarction(OR=0.61,95％CI 0.40-0.91,P=0.01).Although there was a protective trend in atherosclerosis,the fresh fruit intake was not significant(OR=0.76,P=0.31).The dry fruit intake and the three outcomes all showed robust protective effects:atherosclerosis(OR=0.45,P=1.81e-05),coronary heart disease(OR=0.69,P=0.001),myocardial infarction(OR=0.57,P=0.0001).The results of multiple MR methods were consistent,and no significant level of pleiotropy or heterogeneity bias was found.The residual analysis further validated the robustness of the results.Conclusions This study reveals the potential protective effect of fresh fruit and dried fruit intake on atherosclerosis,coronary heart disease and myocardial infarction from the perspective of causal inference through large sample genetic data for the first time,and strengthens the application value of healthy diet model in the field of public health.