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ORIGINAL RESEARCH article

Front. Neurol.
Sec. Stroke
Volume 15 - 2024 | doi: 10.3389/fneur.2024.1408758
This article is part of the Research Topic Advances and controversies in ischemic stroke management: from prevention to diagnosis and acute treatment View all 82 articles

No genetic association between iron deficiency anemia and ischemic stroke and its subtypes: A bidirectional two-sample Mendelian randomization study

Provisionally accepted
Xingyu Chen Xingyu Chen 1Aiping Li Aiping Li 1Wensheng Zhou Wensheng Zhou 1Liping Yao Liping Yao 2*
  • 1 Department of Neurology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, China
  • 2 Department of Neurology, The Third Hospital of Changsha, Changsha, China

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

    Background: Observational researches have suggested a connection between iron deficiency anemia (IDA) and an increased likelihood of ischemic stroke (IS), yet establishing causality is challenging owing to the inherent limitations of such studies, including their vulnerability to confounding factors and the potential for reverse causation. This study employs a bidirectional two-sample Mendelian randomization (MR) approach to assess the causal linkage between IDA and IS and its subtypes. Methods: Identifiable single nucleotide polymorphisms (SNPs) with significant links to either IDA or IS and its subtypes were employed as instrumental variables (IVs). The relationship between IDA and any IS, small vessel stroke (SVS), cardioembolic stroke (CES), and large artery stroke (LAS), was quantified using the inverse variance weighted (IVW) method. Complementary analyses utilizing MR-Egger and weighted median methods further supplemented the IVW findings. Moreover, the leave-one-out analysis, MR-Egger intercept test, MR-PRESSO global test, and Cochrane’s Q test were conducted for sensitivity analyses. Results: This study revealed no correlation between IDA and any IS (IVW method: OR [95% CI] = 0.977 [0.863-1.106]; p = 0.716), LAS (OR [95% CI] = 1.158 [0.771-1.740]; p = 0.479), CES (OR [95% CI] = 1.065 [0.882-1.285]; p = 0.512), or SVS (OR [95% CI] = 1.138 [0.865-1.498]; p = 0.357). Conducting a reverse MR analysis, it was determined that there is no causal connection between any IS, LAS, CES, SVS and IDA (all p > 0.05). Sensitivity analysis indicated that heterogeneity was not significant and no evidence of horizontal pleiotropy was detected. Conclusion: This MR study suggested no causal effect of IDA on IS, LAS, CES, and SVS. Through reverse MR analyses, it was determined that IS and its subtypes did not exert a causal impact on IDA.

    Keywords: iron deficiency anemia, ischemic stroke, small vessel stroke, Cardioembolic stroke, Large artery stroke, Mendelian randomization

    Received: 28 Mar 2024; Accepted: 08 Aug 2024.

    Copyright: © 2024 Chen, Li, Zhou and Yao. 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: Liping Yao, Department of Neurology, The Third Hospital of Changsha, Changsha, China

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