Evidence map›Paper›PMID 40596960›Full record

ArticleBMC neurology2025

Proteome-wide Mendelian randomization and colocalization analysis identify therapeutic targets for stroke.

Xueling Zhao, Menghao He, Desheng Zhou, Zhong Li, Lijuan Liu, Renyi Yang, Xinhua Zhu, Cuilan Gong, Siyang Yan

Abstract read
In one paragraph

Article in BMC neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Xueling ZhaoThe First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, 410007, People's Republic of China.
Menghao HeThe First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, 410007, People's Republic of China.
Desheng ZhouThe First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, 410007, People's Republic of China.
Zhong LiThe First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, 410007, People's Republic of China.
Lijuan LiuThe First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, 410007, People's Republic of China.
Renyi YangHunan University of Chinese Medicine, Changsha, Hunan, 410208, People's Republic of China.
Xinhua ZhuThe First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, 410007, People's Republic of China. 381199814@qq.com.
Cuilan GongThe First Hospital of Traditional Chinese Medicine in Changde, The Changde Affiliated Hospital of Hunan University of Chinese Medicine, Changde, Hunan, 415000, People's Republic of China. cuilan719267108@qq.com.
Siyang YanThe First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, 410007, People's Republic of China. siyangyan@hnucm.edu.cn.

Funding

Healthy China - Buchang Zhiyuan Heart and Brain Health public welfare project HIGHER2023041Hunan Provincial Health Commission Health Research Fund 20232242Hunan Provincial Health Commission Health Research Fund W20243182National Natural Science Foundation of China 82104766Natural Science Foundation of Hunan Province 2022JJ30088Natural Science Foundation of Hunan Province 2023JJ40512Natural Science Foundation of Hunan Province 2024JJ5313Natural Science Foundation of Hunan Province 2024JJ6358Scientific research project of Hunan Provincial Administration of Traditional Chinese Medicine D2024031University-level Fund Project of Hunan University of Chinese Medicine 2022XYLH016University-level Innovative Research Project at Hunan University of Traditional Chinese Medicine 2023CX32
6 · The paper itself

Abstract

backgroundStroke is a leading cause of death and disability worldwide, yet its treatment still faces significant challenges. Mendelian randomization (MR) has been widely used to discover new biomarkers and therapeutic targets. This study aimed to identify therapeutic targets for stroke within the plasma proteome range using MR.

methodsWe conducted a two-sample MR study, evaluating the causal relationships between 2,940 plasma proteins from the UK Biobank-Proteome-wide Association Study (UKB-PPP) and stroke, with further validation in 4,907 plasma proteins from Iceland. Subsequently, drug target proteins were determined using Bayesian colocalization, Summary data-based Mendelian randomization (SMR), and protein-protein interaction (PPI) network construction to validate the role of selected disease-associated proteins.

resultsPreliminary MR analysis identified 11 proteins (LPA, FURIN, MST1, FKBPL, SH2B3, MMP12, F11, ITGAV, DDHD2, VSIR and GAS6) significantly associated with stroke or stroke subtypes. Through SMR and colocalization analysis, 4 potential drug target proteins were identified: FURIN as a potential drug target for stroke and any ischemic stroke, F11 as a potential drug target for cardioembolic stroke, DDHD2 and VSIR as potential drug targets for small vessel stroke. It is worth noting that F11 is currently being used in the development of multiple drugs, FURIN is not only associated with stroke but also appears to have abnormal expression in several cardiovascular diseases. Although research on DDHD2 and VSIR in the context of stroke is relatively limited, current findings indicate that DDHD2 is related to synaptic plasticity, while VSIR is associated with microglia and immune responses.

conclusionThis study found that the plasma proteins FURIN, F11, DDHD2, and VSIR show promise as potential therapeutic targets for stroke and its subtypes, providing genetic evidence to support precision drug development and insights into the underlying pathological mechanisms of stroke. CLINICAL TRIAL NUMBER: Not applicable.

Indexed as

Blood ProteinsMendelian Randomization AnalysisProteomeStrokeBiomarkersFurinGenome-Wide Association StudyHumansProtein Interaction MapsBiomarkersBlood ProteinsFurinProteomeDrug targetsIschemic strokeMendelian randomizationPlasma proteinsStroke

Identifiers

PMID40596960
PMCPMC12211327

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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 OpenQuestion graph.