Lipids, lipid-modifying drug targets with venous thromboembolism: a mendelian randomization study.
- 1Department of Rheumatology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China. Electronic address: [email protected].
- 2Department of Rheumatology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
- 3Department of Endocrinology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Abstract
Background
The role of lipid-lowering therapies (e.g., statins) during anticoagulation for Venous Thromboembolism (VTE) remains unclear. This study investigated the causal role of lipid traits in VTE and evaluated lipid-lowering drug targets using a Mendelian Randomization (MR) approach.Methods
Genetic variants associated with lipid traits and lipid-lowering drug targets were extracted from the Global Lipids Genetics Consortium GWAS. Summary statistics for VTE, Deep Vein Thrombosis (DVT), and Pulmonary Embolism (PE) were obtained from UK Biobank. For associated targets, expression quantitative trait loci data were analyzed using summary-data-based MR. Colocalization analysis assessed shared genetic signals, and molecular docking explored plausible ligand-target binding poses.Results
Higher triglyceride levels were associated with lower VTE (OR = 0.998, 95% CI: 0.996‒1.000, p = 0.035) and DVT risks (OR = 0.998, 95% CI: 0.997‒1.000, p = 0.012). Genetic mimicry of Lipoprotein Lipase (LPL) enhancement was nominally associated with lower VTE odds (OR = 0.997, 95% CI: 0.995‒1.000, p = 0.02) and with lower PE odds after Bonferroni correction (OR = 0.996, 95% CI: 0.994‒0.998, p = 5.29E-06), but not DVT. LPL expression in whole blood showed a significant MR association with PE (OR = 1.001, 95% CI: 1.000‒1.002, p = 0.039) and moderate colocalization (PP.H4 = 0.68). Molecular docking predicted plausible active-site or allosteric binding poses for three LPL agonists (binding energies ≤ -6.8 kcal/mol).Conclusions
Genetically proxied LPL enhancement was nominally associated with modestly lower composite VTE risk and was associated with lower PE risk after multiple-testing correction, although no association was observed for DVT. These findings support a potential role for LPL-related pathways in VTE biology and warrant independent genetic and functional validation before clinical translation.
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BibTeX
@article{nie2026lipids,
title = {{Lipids, lipid-modifying drug targets with venous thromboembolism: a mendelian randomization study.}},
author = {Liuyan Nie and Yongmei Han and Fenping Zheng},
journal = {Clinics (Sao Paulo, Brazil)},
year = {2026},
month = sep,
doi = {10.1016/j.clinsp.2026.101163},
url = {https://europepmc.org/article/MED/42887290},
note = {CC BY},
}
RIS
TY - JOUR
TI - Lipids, lipid-modifying drug targets with venous thromboembolism: a mendelian randomization study.
AU - Liuyan Nie
AU - Yongmei Han
AU - Fenping Zheng
PY - 2026
DA - 2026/09/22
JO - Clinics (Sao Paulo, Brazil)
DO - 10.1016/j.clinsp.2026.101163
UR - https://europepmc.org/article/MED/42887290
AB - Background The role of lipid-lowering therapies (e.g., statins) during anticoagulation for Venous Thromboembolism (VTE) remains unclear. This study investigated the causal role of lipid traits in VTE and evaluated lipid-lowering drug targets using a Mendelian Randomization (MR) approach.Methods Genetic variants associated with lipid traits and lipid-lowering drug targets were extracted from the Global Lipids Genetics Consortium GWAS. Summary statistics for VTE, Deep Vein Thrombosis (DVT), and Pulmonary Embolism (PE) were obtained from UK Biobank. For associated targets, expression quantitative trait loci data were analyzed using summary-data-based MR. Colocalization analysis assessed shared genetic signals, and molecular docking explored plausible ligand-target binding poses.Results Higher triglyceride levels were associated with lower VTE (OR = 0.998, 95% CI: 0.996‒1.000, p = 0.035) and DVT risks (OR = 0.998, 95% CI: 0.997‒1.000, p = 0.012). Genetic mimicry of Lipoprotein Lipase (LPL) enhancement was nominally associated with lower VTE odds (OR = 0.997, 95% CI: 0.995‒1.000, p = 0.02) and with lower PE odds after Bonferroni correction (OR = 0.996, 95% CI: 0.994‒0.998, p = 5.29E-06), but not DVT. LPL expression in whole blood showed a significant MR association with PE (OR = 1.001, 95% CI: 1.000‒1.002, p = 0.039) and moderate colocalization (PP.H4 = 0.68). Molecular docking predicted plausible active-site or allosteric binding poses for three LPL agonists (binding energies ≤ -6.8 kcal/mol).Conclusions Genetically proxied LPL enhancement was nominally associated with modestly lower composite VTE risk and was associated with lower PE risk after multiple-testing correction, although no association was observed for DVT. These findings support a potential role for LPL-related pathways in VTE biology and warrant independent genetic and functional validation before clinical translation.
SN - 1807-5932
SN - 1980-5322
ER -