Evidence map›Paper›PMID 40325450›Full record

ArticleClinical epigenetics2025

Causal associations between epigenetic age and thromboembolism: a bi-directional two-sample Mendelian randomization study.

Bowen Jin, Yunyan Li, Dingyang Li, Chi Jing, Qunshan Sheng

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Article in Clinical epigenetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1 citing paper in PubMed.

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5 · Who and what money

Authors and funding

5 authors.

Bowen JinDepartment of Cardiovascular Surgery, Wuhan Asia Heart Hospital, Wuhan City, 430000, Hubei Province, China. 89097244@sina.com.
Yunyan LiDepartment of Cardiovascular Surgery, Wuhan Asia Heart Hospital, Wuhan City, 430000, Hubei Province, China.
Dingyang LiDepartment of Cardiovascular Surgery, Wuhan Asia Heart Hospital, Wuhan City, 430000, Hubei Province, China.
Chi JingDepartment of Cardiovascular Surgery, Wuhan Asia Heart Hospital, Wuhan City, 430000, Hubei Province, China.
Qunshan ShengDepartment of Cardiovascular Surgery, Wuhan Asia Heart Hospital, Wuhan City, 430000, Hubei Province, China.

Funding

Wuhan Municipal Health Commission guided the project WX2Z29
6 · The paper itself

Abstract

backgroundThromboembolism is one of the most prevalent cardiovascular conditions affecting the elder population. The associations between epigenetic aging and thromboembolism risks remain incompletely elucidated. Through Mendelian randomization (MR), this research seeks to assess the causal links between genetically determined epigenetic aging factors and thromboembolism.

resultsGenetic variants were extracted from genome-wide association studies (GWAS) under stringent threshold as instrumental variables (IVs). Bi-directional two-sample MR analyses were conducted to determine the direction of causal associations. We employed the inverse variance weighted (IVW), weighted median, weighted mode and MR Egger to estimate the causal effect, with sensitivity analyses such as Cochran's Q tests, MR-PRESSO and leave-one-out performed to avoid potential heterogeneity and pleiotropy. Our MR analysis revealed a causal association between intrinsic epigenetic age acceleration and deep vein thrombosis of lower extremities (IVW: OR 0.963, 95% CI 0.934-0.992, P = 0.014), and between the genetically determined levels of plasminogen activator inhibitor-1 and other arterial embolism and thrombosis (IVW: OR 1.000, 95% CI 1.000-1.0005, P = 0.029). Causality was also identified between the genetically predicted levels of FGF23 and other arterial embolism and thrombosis (IVW: OR: 1.661, 95% CI 1.051-2.624, P = 0.029) and arterial embolism and thrombosis of lower extremity artery (IVW: OR 1.68, 95% CI 1.031-2.725, P = 0.037). Moreover, bi-directional MR showed reverse effects between portal vein thrombosis and PhenoAge (IVW: OR 0.871, 95% CI 0.765-0.992, P = 0.037) and between venous thromboembolism and GrimAge (IVW: OR 1.186, 95% CI 1.048-1.341, P = 0.007). Sensitivity analysis using Cochran's Q tests, MR-PRESSO and leave-one-out excluded the influence of heterogeneity, horizontal pleiotropy, and outliers.

conclusionOur results identified a causal association between genetically predicted epigenetic aging factors and thromboembolism. The findings highlight the necessity for further exploration into the underlying etiology of thromboembolism.

Indexed as

AgingEpigenesis, GeneticMendelian Randomization AnalysisThromboembolismAgedAge FactorsFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMalePlasminogen Activator Inhibitor 1Polymorphism, Single NucleotidePlasminogen Activator Inhibitor 1Causal inferenceEpigenetic aging clocksMendelian randomizationThromboembolism

Identifiers

PMID40325450
PMCPMC12051321

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