Evidence map›Paper›PMID 40404751›Full record

ArticleScientific reports2025

Trans-ethnic Mendelian randomization analysis of membranous nephropathy and peripheral artery disease with mediating effects of thrombomodulin.

Juhong Pan, Xingyue Huang, Yueying Chen, Nan Jiang, Yuxin Guo, Shiyuan Zhou, Yao Zhang, Bo Hu, Qing Deng, Qing Zhou

Abstract read
In one paragraph

Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Juhong Pan *Department of Ultrasound Imaging, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
Xingyue Huang *Department of Ultrasound Imaging, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
Yueying ChenDepartment of Ultrasound Imaging, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
Nan JiangDepartment of Ultrasound Imaging, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
Yuxin GuoDepartment of Ultrasound Imaging, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
Shiyuan ZhouDepartment of Ultrasound Imaging, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
Yao ZhangDepartment of Ultrasound Imaging, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
Bo HuDepartment of Ultrasound Imaging, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
Qing DengDepartment of Ultrasound Imaging, Renmin Hospital of Wuhan University, Wuhan, 430060, China. wudadq@163.com.
Qing ZhouDepartment of Ultrasound Imaging, Renmin Hospital of Wuhan University, Wuhan, 430060, China. qingzhou@whu.edu.cn.

Funding

Cross-Innovation Talent Project of People's Hospital of Wuhan University JCRCYR-2022-011National Natural Science Foundation of China 81971624, 82271999
6 · The paper itself

Abstract

This study employed a trans-ethnic two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between membranous nephropathy (MN) and peripheral artery disease (PAD). In European populations, MN exhibited a significant positive causal effect on PAD (discovery: OR = 1.040, P = 0.028; validation: OR = 1.028, P = 0.031), whereas no such association was observed in East Asians (P > 0.05). A two-step mediation analysis identified several proteins influenced by MN, including thrombomodulin (TM) (β = 0.031, P = 0.001), macrophage colony-stimulating factor 1 (MCSF1) (β = 0.239, P = 0.015), stem cell factor (SCF) (β = 0.028, P = 0.002), and tissue factor (TF) (β = 0.031, P = 0.001), while MN negatively affected interleukin-1β (IL-1β) (β=-0.049, P = 0.015) and hepatocyte growth factor (HGF) (β=-0.027, P = 0.005). Multivariable MR analysis confirmed that only TM had an independent positive causal effect on PAD (β = 0.225, P < 0.001), and mediation analysis further validated TM as a significant mediator in the MN-to-PAD pathway (Z = 2.823, P = 0.048). Sensitivity analyses detected no significant pleiotropy or heterogeneity, supporting the robustness of our findings. This study highlights crucial ethnic differences in MN-associated PAD risk and underscores the importance of population-specific research. TM may serve as a potential therapeutic target for PAD prevention in MN patients, particularly those of European ancestry, providing novel insights into kidney-vascular disease mechanisms.

Indexed as

Glomerulonephritis, MembranousMendelian Randomization AnalysisPeripheral Arterial DiseaseThrombomodulinEast Asian PeopleGenetic Predisposition to DiseaseHepatocyte Growth FactorHumansPolymorphism, Single NucleotideWhite PeopleHepatocyte Growth FactorTHBD protein, humanThrombomodulinMediationMembranous nephropathyMendelian randomizationPeripheral artery diseaseThrombomodulin

Identifiers

PMID40404751
PMCPMC12098656

What Socratic holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.