Evidence map›Paper›PMID 40369036›Full record

ArticleScientific reports2025

Identification of causal plasma metabolite biomarkers for ischemic stroke using Mendelian randomization and mediation analysis.

Jian Lyu, Fumei Liu, Yan Chai, Xiting Wang, Yi Liu, Yanming Xie

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

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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

6 authors.

Jian LyuNMPA Key Laboratory for Clinical Research and Evaluation of Traditional Chinese Medicine & National Clinical Research Center for Chinese Medicine Cardiology, XiYuan Hospital, China Academy of Chinese Medical Sciences, No.1 Xiyuan playground Road, Haidian District, Beijing, 100091, PR China. dr.jianlyu-tcm@outlook.com.
Fumei LiuInstitute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, No.16 Nanxiaojie, Inner Dongzhimen, Dongcheng District, Beijing, 100700, PR China.
Yan ChaiDepartment of Epidemiology, University of California, 405 Hilgard Avenue, Los Angeles, 90095, CA, USA.
Xiting WangAcademy of Mathematics and Systems Science, Chinese Academy of Sciences, No. 55 Zhongguancun East Road, Beijing, 100190, China. wangxiting@amss.ac.cn.
Yi LiuInstitute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, No.16 Nanxiaojie, Inner Dongzhimen, Dongcheng District, Beijing, 100700, PR China. dr.liuyi93@gmail.com.
Yanming XieInstitute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, No.16 Nanxiaojie, Inner Dongzhimen, Dongcheng District, Beijing, 100700, PR China. ktzu2018@163.com.

Funding

National Key Research and Development Program of China 2018YFC1707400National Natural Science Foundation of China 82205101
6 · The paper itself

Abstract

The Global Burden of Disease Study 2021 reports that stroke remains a leading cause of death, with ischemic stroke (IS) presenting significant challenges in screening, prevention, and treatment. We explored the causal effects of 1,400 plasma metabolites on IS outcomes using a two-sample Mendelian randomization (MR) framework. We assessed causal relationships between IS and 11 common clinical risk factors and further examined these relationships for metabolites. Mediation analysis identified mechanisms for metabolites affecting both IS and its risk factors. Finally, a phenome-wide association study (PheWAS) MR analysis evaluated the side effects and additional indications of IS-associated metabolites across 3,948 phenotypes from the UKBB GWAS. Nineteen metabolites showed a causal relationship with IS. MR analysis confirmed body mass index (BMI), high-density lipoprotein (HDL), systolic blood pressure (SBP), diastolic blood pressure (DBP), and type 2 diabetes (T2D) as risk factors for IS. Among 136 metabolites associated with at least one IS risk factor, 132 were linked to risk factors but not directly to IS. BMI, DBP, and coffee intake mediated the causal relationship between IS and the levels of 1-stearoyl-GPG (18:0), 1-oleoyl-2-linoleoyl-GPE (18:1/18:2), Octadecadienedioate (C18:2-DC), and X-24,951. Phe-MR analysis indicated that these metabolites were protective and affected other indications similarly to IS. Our findings reveal causal pathways and identify four potential biomarkers for IS, providing new insights for its screening, prevention, and treatment.

Indexed as

BiomarkersIschemic StrokeMendelian Randomization AnalysisBlood PressureBody Mass IndexDiabetes Mellitus, Type 2Genome-Wide Association StudyHumansMaleMediation AnalysisPolymorphism, Single NucleotideRisk FactorsBiomarkersBiomarkersHuman plasma metabolomicsIschemic strokeMediating effectsMendelian randomization

Identifiers

PMID40369036
PMCPMC12078489

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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.