Metabolites and coronary heart disease: A two sample Mendelian randomization

IF 1.9 Q3 PERIPHERAL VASCULAR DISEASE

International Journal of Cardiology Cardiovascular Risk and Prevention Pub Date : 2025-01-09 DOI:10.1016/j.ijcrp.2025.200365

Yang Sheng , Feng Gao , Zhenyu Zhu , Tianjie Zhang , Wei Zhang

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Abstract

Background

In observational studies, circulating metabolites were related to Coronary heart disease (CHD), but their causal relationship is unknown. In this study, we sought to determine a bidirectional causal relationship between circulating metabolites and CHD and to explore whether circulating metabolites are associated with a decreased risk of CHD.

Methods

In our two-sample Mendelian randomization (MR) study, the top SNPs associated with circulating metabolites (n = 24, 925) as well as CHD (n = 86, 995) were acquired from publicly available genome-wide association studies (GWAS). The SNPs estimates were pooled using inverse variance weighted meta-analysis, with median weighted by sensitivity analyses, MR Egger and MR Pleiotropy Residual Sum and Outlier (PRESSO).

Results

Free cholesterol in large LDL(p, 6.9E-07; OR, 2.2; 95%CI,1.6–3.0),total cholesterol in medium LDL(p, 1.0E-06; OR, 1.8; 95%CI,1.4–2.3)Total cholesterol in LDL (p,1.43083E-05; OR,1.7; 95%CI, 1.3–2.2). Phospholipids in medium LDL (p,0.0; OR,1.6; 95%CI, 1.2–2.1); Total cholesterol in small VLDL (p,0.0; OR, 1.8; 95%CI, 1.2–2.7); Triglycerides in small VLDL (p,0.0, OR, 1.3; 95%CI, 1.0–1.6); Free cholesterol in small VLDL (p,0.0; OR,1.3; 95%CI, 1.0–1.7); Phospholipids in small VLDL (p,0.0; OR,1.3, 95%CI,1.0–1.7); Triglycerides in small HDL (p,0.0, OR,1.3,95%CI,1.0–1.7); Alanine (0.0, OR,1.2,95%CI,1.0–1.6) were positively associated with CHD. Phospholipids in medium HDL (p,0.0, OR,0.8; 95%CI, 0.6–0.9) might have a protective effect on CHD, which were negatively associated with CHD.

Conclusions

Our MR analysis demonstrated a protective effect of Phospholipids in medium HDL, and a potentially anti-protective effect of Free cholesterol in large LDL, Total cholesterol in medium LDL, Total cholesterol in LDL, Phospholipids in medium LDL, Total cholesterol in small VLDL, Triglycerides in small VLDL, Free cholesterol in small VLDL, Phospholipids in small VLDL, Triglycerides in small HDL, Alanine on the pathogenesis of CHD. Additional studies are required to translate the findings into practice.

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代谢物与冠心病：两样本孟德尔随机化

在观察性研究中，循环代谢物与冠心病有关，但其因果关系尚不清楚。在这项研究中，我们试图确定循环代谢物与冠心病之间的双向因果关系，并探讨循环代谢物是否与冠心病风险降低有关。方法在我们的两样本孟德尔随机化（MR）研究中，从公开的全基因组关联研究（GWAS）中获得与循环代谢物（n = 24,925）和冠心病（n = 86,995）相关的顶级snp。snp估计值采用反方差加权荟萃分析合并，中位数通过敏感性分析、MR Egger和MR多效性残差和离群值（PRESSO）加权。结果大LDL游离胆固醇(p, 6.90 e -07；或者,2.2;95%CI, 1.6-3.0)，中LDL总胆固醇(p, 1.0E-06；或者,1.8;95%CI, 1.4-2.3) LDL总胆固醇(p,1.43083E-05；或者,1.7;95%可信区间,1.3 - -2.2)。中等LDL中磷脂含量(p,0.0；或者,1.6;95%置信区间,1.2 - -2.1);小VLDL总胆固醇(p,0.0；或者,1.8;95%置信区间,1.2 - -2.7);小VLDL中的甘油三酯(p,0.0， OR, 1.3；95%置信区间,1.0 - -1.6);小VLDL游离胆固醇(p,0.0；或者,1.3;95%置信区间,1.0 - -1.7);小VLDL中的磷脂含量(p,0.0；或者1.3,95% ci, 1.0 - -1.7);小HDL中的甘油三酯（p,0.0， OR,1.3,95%CI, 1.0-1.7）；丙氨酸（0.0，OR,1.2,95%CI, 1.0-1.6）与冠心病呈正相关。中等高密度脂蛋白中的磷脂含量(p,0.0， OR,0.8；95%CI, 0.6-0.9)可能对冠心病有保护作用，与冠心病呈负相关。结论sour MR分析表明，磷脂对中度HDL具有保护作用，而大LDL游离胆固醇、中LDL总胆固醇、LDL总胆固醇、中LDL磷脂、小VLDL总胆固醇、小VLDL甘油三酯、小VLDL游离胆固醇、小VLDL磷脂、小HDL甘油三酯、丙氨酸对冠心病发病有潜在的抗保护作用。需要进一步的研究来将这些发现转化为实践。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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