Lipid metabolism-associated metabolites on cardiovascular diseases: a two-sample Mendelian randomized study

BackgroundThere is a growing body of evidence indicating that metabolites are associated with an increased risk of cardiovascular diseases (CVDs), the underlying causality of these associations remains largely unchallenged. Given the inherent difficulty in establishing causality using epidemiologica...

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Main Authors: Jia-Le Chen, Xin-Yi Lu, Dao-Zhen Chen, Yu Chen
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-03-01
Series:Frontiers in Cardiovascular Medicine
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Online Access:https://www.frontiersin.org/articles/10.3389/fcvm.2025.1445732/full
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author Jia-Le Chen
Jia-Le Chen
Xin-Yi Lu
Xin-Yi Lu
Dao-Zhen Chen
Dao-Zhen Chen
Yu Chen
author_facet Jia-Le Chen
Jia-Le Chen
Xin-Yi Lu
Xin-Yi Lu
Dao-Zhen Chen
Dao-Zhen Chen
Yu Chen
author_sort Jia-Le Chen
collection DOAJ
description BackgroundThere is a growing body of evidence indicating that metabolites are associated with an increased risk of cardiovascular diseases (CVDs), the underlying causality of these associations remains largely unchallenged. Given the inherent difficulty in establishing causality using epidemiological data, we employed the technique of Mendelian randomization to investigate the potential role of plasma metabolite factors in influencing the risk of CVDs.MethodsThe exposure was based on 1,400 plasma metabolites, and outcomes involved four CVD datasets from public databases. Initial causality was assessed by inverse variance weighting (IVW), followed by sensitivity analyses using MR-Egger regression, weighted median, and Multiple Effectiveness Residual Sums and Outliers (MR-PRESSO) method. Potential heterogeneity and multivalence were assessed using the MR-Egger intercept and Cochran's Q statistic. After Bonferroni correction, causal associations were found to be significant with p-values less than 0.05. All statistical analyses were rigorously executed in R software.ResultsOur findings identified causal relationships between 15 metabolites and cardiovascular disease. Of these, 4 were associated with AA (aortic aneurysm), 7 with atrial fibrillation and flutter, 2 with HF (heart failure), and 3 with stroke.ConclusionThis is the first systematic mendelian randomization analysis using genome-wide data to assess the causal relationship between serum metabolites and different cardiovascular diseases, providing preliminary evidence for the impact of lipid metabolism disorders on cardiovascular disease risk.
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spelling doaj-art-f7e207c8e2464dcab55c8a8761c38c9d2025-08-20T03:44:28ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2025-03-011210.3389/fcvm.2025.14457321445732Lipid metabolism-associated metabolites on cardiovascular diseases: a two-sample Mendelian randomized studyJia-Le Chen0Jia-Le Chen1Xin-Yi Lu2Xin-Yi Lu3Dao-Zhen Chen4Dao-Zhen Chen5Yu Chen6Hospital Infection Management Section, Wujin Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Changzhou, Jiangsu, ChinaWuxi Maternal and Child Health Hospital, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, ChinaWuxi Maternal and Child Health Hospital, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, ChinaWuxi Medical Center, Nanjing Medical University, Wuxi, Jiangsu, ChinaWuxi Maternal and Child Health Hospital, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, ChinaWuxi Medical Center, Nanjing Medical University, Wuxi, Jiangsu, ChinaWuxi Maternal and Child Health Hospital, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, ChinaBackgroundThere is a growing body of evidence indicating that metabolites are associated with an increased risk of cardiovascular diseases (CVDs), the underlying causality of these associations remains largely unchallenged. Given the inherent difficulty in establishing causality using epidemiological data, we employed the technique of Mendelian randomization to investigate the potential role of plasma metabolite factors in influencing the risk of CVDs.MethodsThe exposure was based on 1,400 plasma metabolites, and outcomes involved four CVD datasets from public databases. Initial causality was assessed by inverse variance weighting (IVW), followed by sensitivity analyses using MR-Egger regression, weighted median, and Multiple Effectiveness Residual Sums and Outliers (MR-PRESSO) method. Potential heterogeneity and multivalence were assessed using the MR-Egger intercept and Cochran's Q statistic. After Bonferroni correction, causal associations were found to be significant with p-values less than 0.05. All statistical analyses were rigorously executed in R software.ResultsOur findings identified causal relationships between 15 metabolites and cardiovascular disease. Of these, 4 were associated with AA (aortic aneurysm), 7 with atrial fibrillation and flutter, 2 with HF (heart failure), and 3 with stroke.ConclusionThis is the first systematic mendelian randomization analysis using genome-wide data to assess the causal relationship between serum metabolites and different cardiovascular diseases, providing preliminary evidence for the impact of lipid metabolism disorders on cardiovascular disease risk.https://www.frontiersin.org/articles/10.3389/fcvm.2025.1445732/fullplasma metabolitescardiovascular diseaseglycolipid metabolic disordersMendelian randomizationsingle-nucleotide polymorphismsrisk factors
spellingShingle Jia-Le Chen
Jia-Le Chen
Xin-Yi Lu
Xin-Yi Lu
Dao-Zhen Chen
Dao-Zhen Chen
Yu Chen
Lipid metabolism-associated metabolites on cardiovascular diseases: a two-sample Mendelian randomized study
Frontiers in Cardiovascular Medicine
plasma metabolites
cardiovascular disease
glycolipid metabolic disorders
Mendelian randomization
single-nucleotide polymorphisms
risk factors
title Lipid metabolism-associated metabolites on cardiovascular diseases: a two-sample Mendelian randomized study
title_full Lipid metabolism-associated metabolites on cardiovascular diseases: a two-sample Mendelian randomized study
title_fullStr Lipid metabolism-associated metabolites on cardiovascular diseases: a two-sample Mendelian randomized study
title_full_unstemmed Lipid metabolism-associated metabolites on cardiovascular diseases: a two-sample Mendelian randomized study
title_short Lipid metabolism-associated metabolites on cardiovascular diseases: a two-sample Mendelian randomized study
title_sort lipid metabolism associated metabolites on cardiovascular diseases a two sample mendelian randomized study
topic plasma metabolites
cardiovascular disease
glycolipid metabolic disorders
Mendelian randomization
single-nucleotide polymorphisms
risk factors
url https://www.frontiersin.org/articles/10.3389/fcvm.2025.1445732/full
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