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ORIGINAL RESEARCH article

Front. Neurol.
Sec. Stroke
Volume 15 - 2024 | doi: 10.3389/fneur.2024.1437153
This article is part of the Research Topic Blood-Based Cellular and Molecular Biomarkers in Acute Ischemic Stroke and Hemorrhagic Stroke - Volume II View all 4 articles

Genetic causality of lipidomic and immune cell profiles in ischemic stroke

Provisionally accepted
Haohao CHEN Haohao CHEN 1,2Zequn Zheng Zequn Zheng 3,4*Xiaorui Cai Xiaorui Cai 5Shunxian Li Shunxian Li 6Manli Chen Manli Chen 6Jiaming Wu Jiaming Wu 6Wenzhen He Wenzhen He 6*Fenfei Gao Fenfei Gao 1*
  • 1 Department of Pharmacy, Shantou University Medical College,, Shantou, China
  • 2 Department of Pharmacy, First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong Province, China
  • 3 Department of Cardiology, First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong Province, China
  • 4 Clinical Research Center, First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong Province, China
  • 5 The Affiliated Cancer Hospital of Shantou University Medical College, Shantou, China
  • 6 Department of Neurology, First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong Province, China

The final, formatted version of the article will be published soon.

    Background: Ischemic stroke (IS) is a global health issue linked to lipid metabolism and immune cell responses. This study uses Mendelian randomization (MR) to identify genetic risk factors for IS subtypes using comprehensive genetic data from lipidomic and immune cell profiles. Methods: We assessed genetic susceptibility to IS across 179 lipids and 731 immune cell phenotypes using instrumental variables (IVs) from recent genome-wide association studies. A two-sample MR approach evaluated correlations, and a two-step MR mediation analysis explored the role of immune cell phenotypes in the lipid-IS pathway. Sensitivity analyses, including MR-Egger and Cochran Q tests, ensured robust results. Results: Genetic IVs for 162 lipids and 614 immune cell phenotypes were identified. Significant genetic causality was found between 35 lipids and large artery stroke (LAS), with 12 as risk factors (sterol esters, phosphatidylcholines, phosphatidylethanolamines) and 23 as protective factors (phosphatidylcholines, phosphatidylethanolamines, phosphatidylinositols). For small vessel stroke (SVS), 8 as risk factors (sterol esters, phosphatidylcholines), and 2 as protective factors (phosphatidylinositol, sphingomyelin). For cardioembolic stroke (CS), 2 as risk factors, and 4 as protective factors. Mediation analysis revealed that CCR2 on granulocytes, CD11c on CD62L+ myeloid dendritic cells, and FSC-A on granulocytes mediated the lipid-immune cell-LAS pathway, while CD4 on activated CD4 regulatory T cells and CD4 on activated & secreting CD4 regulatory T cells mediated the lipid-immune cell-SVS pathway.Conclusions: This study identifies genetic links between specific lipids and IS subtypes, highlights immune cells' role in IS risk and mediation, suggests new therapeutic targets, and uncovers IS genetic drivers.

    Keywords: ischemic stroke, Large artery stroke, small vessel stroke, Cardioembolic stroke, lipidomic, Immune cell phenotypes, Mendelian randomization, genetic causality

    Received: 05 Jun 2024; Accepted: 09 Sep 2024.

    Copyright: © 2024 CHEN, Zheng, Cai, Li, Chen, Wu, He and Gao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Zequn Zheng, Department of Cardiology, First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong Province, China
    Wenzhen He, Department of Neurology, First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, Guangdong Province, China
    Fenfei Gao, Department of Pharmacy, Shantou University Medical College,, Shantou, China

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