Volume 23 Issue 12
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CHEN Shixuan, CHEN Zhenzhen, CHEN Wenci, JI Jing. Causal association between iron homeostasis and functional outcome after ischemic stroke: a two-sample univariate and multivariate Mendelian randomization study[J]. Chinese Journal of General Practice, 2025, 23(12): 2017-2021. doi: 10.16766/j.cnki.issn.1674-4152.004281
Citation: CHEN Shixuan, CHEN Zhenzhen, CHEN Wenci, JI Jing. Causal association between iron homeostasis and functional outcome after ischemic stroke: a two-sample univariate and multivariate Mendelian randomization study[J]. Chinese Journal of General Practice, 2025, 23(12): 2017-2021. doi: 10.16766/j.cnki.issn.1674-4152.004281
shu

Causal association between iron homeostasis and functional outcome after ischemic stroke: a two-sample univariate and multivariate Mendelian randomization study

doi: 10.16766/j.cnki.issn.1674-4152.004281
  • 1.

    Department of Rehabilitation Medicine, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, Zhejiang Chinese Medical University, Wenzhou, Zhejiang 325000, China

Funds:

 2021ZB276

 Y20240897

  • Received Date: 2024-12-25
    Available Online: 2026-03-13
    Abstract
  •   Objective  Observational studies suggest an association between serum iron homeostasis and functional outcome after ischemic stroke, but this association is susceptible to confounders and reverse causality. This study utilizes Mendelian randomization (MR) to minimize confounders and assess whether an imbalance in iron homeostasis is causally associated with poor functional outcome after ischemic stroke.  Methods  GWAS data related to iron homeostasis, including serum iron, ferritin, total iron-binding capacity, transferrin saturation, and liver iron content, were selected as exposure variables. GWAS data on functional outcome at three months after ischemic stroke were used as outcome variables. Firstly, univariable MR (UVMR) analysis was conducted, with the random effects inverse variance weighting (IVW) serving as the primary analysis method, and MR-Egger and weighted median (WME) methods as supplementary analyses. Cochran's Q and Rucker's Q tests were employed to assess heterogeneity, while the MR-Egger intercept was used to test for horizontal pleiotropy. Additionally, multivariable MR (MVMR) analysis was performed to evaluate the causal effect after adjusting for BMI.  Results  A total of 117 single nucleotide polymorphisms (SNPs) were ultimately selected as instrumental variables for iron homeostasis, with all SNPs having an F-value greater than 10. The UVMR-IVW results indicated a causal association between serum iron, transferrin saturation, liver iron content, and poor functional outcome at three months after ischemic stroke (P < 0.05). The MVMR-IVW results, adjusted for BMI, showed that serum iron and transferrin saturation maintained significant causal associations with poor functional outcome at three months after ischemic stroke (P < 0.05). All results from MR-Egger and WME methods were consistent with IVW, and no evidence of heterogeneity or horizontal pleiotropy was found.  Conclusion  There is a significant causal association between serum iron overload and poor functional outcome at three months after ischemic stroke.

     

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