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Endocrine-disrupting chemical-induced gene networks confer coronary heart disease risk revealed by causal inference and single-cell analyses.

Tao Yao·Yun-Lu Lin·Luo-Xiang Fang·Yu-Tian Wang·Lan-Feng Zhou·Ning Zhang·Gang Chen
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Abstract

BACKGROUND: Endocrine-disrupting chemicals (EDCs) are linked to coronary heart disease (CHD), but underlying mechanisms remain unclear. We aimed to identify EDC-related genes and evaluate their causal roles in CHD. METHODS: We curated EDC-related genes from a compound-gene interaction database and integrated them with CHD genome-wide association study (GWAS) summary statistics and tissue-specific expression quantitative trait loci (eQTL) data. Two-sample Mendelian randomization (MR) and Bayesian colocalization were applied to infer causality. Functional enrichment, single-cell RNA sequencing of human coronary arteries, and EDC-gene networks were further analyzed. RESULTS: After FDR correction, 39 genes were significantly associated with CHD risk via MR. Four genes-ZNF827, FCHO1, IPO9 (protective), and RPL13 (risk-increasing)-showed strong colocalization (PPH4 > 0.9). Pathway and single-cell analyses of coronary artery tissue indicated that vascular and immune pathways mediate these effects. An interaction network highlighted associations between specific EDCs and candidate genes implicated in CHD susceptibility. CONCLUSION: This integrative genomic study provides evidence that EDCs influence CHD susceptibility through distinct gene networks, revealing potential mechanisms and molecular targets for prevention and therapy.

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HumansGene Regulatory NetworksEndocrine DisruptorsGenome-Wide Association StudyCoronary DiseaseSingle-Cell AnalysisQuantitative Trait LociMendelian Randomization AnalysisGenetic Predisposition to DiseaseChemical-gene associationsCoronary heart diseaseEndocrine-disrupting chemicalsMendelian randomizationJournal Article

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Tao Yao, Yun-Lu Lin, Luo-Xiang Fang, Yu-Tian Wang, Lan-Feng Zhou, Ning Zhang, Gang Chen. 2026-08-05. Endocrine-disrupting chemical-induced gene networks confer coronary heart disease risk revealed by causal inference and single-cell analyses.. https://doi.org/10.1016/j.fct.2026.116325

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Journal Article resourceGene Regulatory Networks subjectGenetic Predisposition to Disease subjectGenome-Wide Association Study subjectHumans subjectJournal Article subjectMendelian Randomization Analysis subjectMendelian randomization subjectSingle-cell RNA sequencing method

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