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ORIGINAL RESEARCH article

Front. Aging Neurosci.
Sec. Parkinson’s Disease and Aging-related Movement Disorders
Volume 16 - 2024 | doi: 10.3389/fnagi.2024.1416014
This article is part of the Research Topic Common pathophysiology underpinning Parkinson's disease and other neurodegenerative diseases View all 10 articles

Abdominal muti-organ iron content and the risk of Parkinson's disease： A Mendelian randomization study

Provisionally accepted
Mingrui Yang Mingrui Yang 1,2Cheng Tang Cheng Tang 1,2*Fei Peng Fei Peng 1,2Chaotian Luo Chaotian Luo 1,2Guowei Chen Guowei Chen 1,2*Rong Kong Rong Kong 1,2*Peng Peng Peng Peng 1,3*
  • 1 Department of Radiology, First Affiliated Hospital, Guangxi Medical University, Nanning, China
  • 2 Guangxi Medical University, Nanning, Guangxi Zhuang Region, China
  • 3 Guangxi Key Laboratory of Prevention and Treatment of Thalassemia, Nanning, Guangxi Zhuang Region, China

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

    Background: To evaluate the causal relationship between abdominal multi-organ iron content and PD risk using publicly available genome-wide association study (GWAS) data.Methods:We conducted MR analysis to assess the effects of iron content in various abdominal organs on PD risk, followed by reverse analysis. Additionally, MVMR analysis evaluated the independent effects of organ-specific iron content on PD. We utilized genetic variation data from the UK Biobank, including liver iron content (n=32,858), spleen iron content (n=35,324), and pancreas iron content (n=25,617), as well as summary-level data for Parkinson's disease from the FinnGen (n=218,473) and two other large GWAS datasets of European populations (First dataset n=480,018; Second dataset n=2,829). The primary MR analysis used the inverse variance-weighted (IVW) method, confirmed by MR-Egger and weighted median methods. Sensitivity analysis was performed to address potential pleiotropy and heterogeneity. Observational cohort results were validated through replication cohort analysis, followed by meta-analysis.Results: IVW analysis revealed a causal relationship between increased liver iron content and elevated risk of PD (OR=1.27; 95% CI: 1.05-1.53; p =0.015). No significant causal relationship was observed between spleen (OR=1.00; 95% CI: 0.76-1.32; p =0.983) and pancreatic (OR=0.93; 95% CI: 0.72-1.20; p =0.573) iron content and increased risk of PD. Meta-analysis of GWAS data for PD from three different sources using the random-effects IVW method showed a statistically significant causal relationship between liver iron content and the occurrence of PD (OR=1.17, 95% CI: 1.01-1.35；p =0.012).Conclusion: This study presents evidence from Mendelian randomization (MR) analysis indicating a significant causal link between increased liver iron content and a higher risk of Parkinson's disease (PD). These findings suggest that interventions targeting body iron metabolism, particularly liver iron levels, may be effective in preventing PD.

    Keywords: abdominal multi-organ, Iron content, Parkinson's disease, iron metabolism, Mendelian randomization

    Received: 11 Apr 2024; Accepted: 30 Jul 2024.

    Copyright: © 2024 Yang, Tang, Peng, Luo, Chen, Kong and Peng. 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:
    Cheng Tang, Department of Radiology, First Affiliated Hospital, Guangxi Medical University, Nanning, China
    Guowei Chen, Department of Radiology, First Affiliated Hospital, Guangxi Medical University, Nanning, China
    Rong Kong, Department of Radiology, First Affiliated Hospital, Guangxi Medical University, Nanning, China
    Peng Peng, Department of Radiology, First Affiliated Hospital, Guangxi Medical University, Nanning, China

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