AUTHOR=Yang Mingrui , Tang Cheng , Peng Fei , Luo Chaotian , Chen Guowei , Kong Rong , Peng Peng 

TITLE=Abdominal multi-organ iron content and the risk of Parkinson’s disease: a Mendelian randomization study

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=16

YEAR=2024

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2024.1416014

DOI=10.3389/fnagi.2024.1416014

ISSN=1663-4365

ABSTRACT=<sec id="sec1"><title>Background</title><p>To evaluate the causal relationship between abdominal multi-organ iron content and PD risk using publicly available genome-wide association study (GWAS) data.</p></sec><sec id="sec2"><title>Methods</title><p>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 (<italic>n</italic> = 32,858), spleen iron content (<italic>n</italic> = 35,324), and pancreas iron content (<italic>n</italic> = 25,617), as well as summary-level data for Parkinson’s disease from the FinnGen (<italic>n</italic> = 218,473) and two other large GWAS datasets of European populations (First dataset <italic>n</italic> = 480,018; Second dataset <italic>n</italic> = 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.</p></sec><sec id="sec3"><title>Results</title><p>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; <italic>p</italic> = 0.015). No significant causal relationship was observed between spleen (OR = 1.00; 95% CI: 0.76–1.32; <italic>p</italic> = 0.983) and pancreatic (OR = 0.93; 95% CI: 0.72–1.20; <italic>p</italic> = 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; <italic>p</italic> = 0.012).</p></sec><sec id="sec4"><title>Conclusion</title><p>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.</p></sec>