Table_2_Identifying atheroprotective fruits and vegetables by Mendelian Randomization analysis.docx

BackgroundFruits and vegetables (FVs) are widely believed to mitigate the risk of atherosclerosis (AS). However, the causal relationships between specific FVs and AS risk factors remain unclear.
MethodsThis study performed two-sample Mendelian Randomization (MR) analysis to infer the causality of the intake of 28 kinds of FVs with AS, as well as its risk factors including blood low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and C-reactive protein (CRP). GWAS genetic data for these exposures and outcomes were extracted from the IEU open GWAS project. Heterogeneity was evaluated using both Inverse Variance Weighted (IVW) and MR-Egger methods. MR-Egger regression was specifically deployed to detect potential pleiotropy. Furthermore, a “leave-one-out” sensitivity analysis was conducted to determine the impact of each individual single nucleotide polymorphism (SNP) on the combined outcome.
ResultsThe analysis confirms a causal relationship between total fruit consumption and reduced levels of LDL-C (OR = 0.911, p = 0.007) and CRP (OR = 0.868, p = 0.008). Similarly, total vegetable intake is also causally associated with a reduction in CRP levels (OR = 0.858, p = 0.018). Specifically, garlic intake exhibits the most significant causal relationship with reduced risk of AS (OR = 0.985, p = 0.036) and also causally associated with lower levels of LDL-C and TG. Berry (OR = 0.929, p = 0.010) and potato (OR = 0.957, p = 0.020) intake both display a significant causal negative association with TG levels, while peach/nectarine consumption is significantly associated with reduced CRP levels (OR = 0.913, p = 0.010).
ConclusionThis is the first MR study that systemically examined the causality between commonly consumed FVs and AS. Our findings highlight the atheroprotective effects of various FVs, particularly garlic, on cardiovascular health and the importance of tailored nutritional recommendations to prevent AS.

背景
水果与蔬菜（Fruits and Vegetables, FVs）被广泛认为可降低动脉粥样硬化（Atherosclerosis, AS）的发病风险。然而，特定种类的FVs与AS风险因素之间的因果关联仍未明确。
方法
本研究采用两样本孟德尔随机化（two-sample Mendelian Randomization, MR）分析，探究28种FVs的摄入与AS及其风险因素（包括血液低密度脂蛋白胆固醇（low-density lipoprotein cholesterol, LDL-C）、甘油三酯（triglycerides, TG）与C反应蛋白（C-reactive protein, CRP））之间的因果关联。本研究从IEU开放GWAS项目中提取上述暴露因素与结局变量的全基因组关联分析（Genome-Wide Association Study, GWAS）遗传数据。采用逆方差加权（Inverse Variance Weighted, IVW）与MR-Egger两种方法评估异质性，并专门通过MR-Egger回归检测潜在的多效性。此外，本研究开展留一法敏感性分析，以明确每个单核苷酸多态性（single nucleotide polymorphism, SNP）对合并结局的影响。
结果
本分析证实，总水果摄入量与LDL-C（比值比（Odds Ratio, OR）=0.911，P=0.007）及CRP（OR=0.868，P=0.008）水平降低存在因果关联。同样，总蔬菜摄入量也与CRP水平降低存在因果关联（OR=0.858，P=0.018）。具体而言，大蒜摄入与AS风险降低的因果关联最为显著（OR=0.985，P=0.036），同时其摄入也与LDL-C及TG水平降低存在因果关联。浆果（OR=0.929，P=0.010）与马铃薯（OR=0.957，P=0.020）的摄入均与TG水平降低存在显著的负向因果关联，而桃/油桃的摄入则与CRP水平降低显著相关（OR=0.913，P=0.010）。
结论
本研究是首个系统性探究日常食用FVs与AS之间因果关联的MR研究。本研究结果凸显了多种FVs（尤其是大蒜）对心血管健康的抗动脉粥样硬化作用，以及制定个性化营养建议以预防AS的重要性。