ArticlePLoS medicine2013
Serum iron levels and the risk of Parkinson disease: a Mendelian randomization study.
Article in PLoS medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT01351467 (Ongoing, Web-Based Genome-Wide Association Studies for Targeted Disease Initiatives), which is not on this map. Cited by 84 papers, 7 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Ongoing, Web-Based Genome-Wide Association Studies for Targeted Disease Initiatives
Who cites it
84 citing papers in PubMed, 7 syntheses or guidelines pooled it, 187 citations in OpenAlex.
- Genome-wide meta-analysis of iron status biomarkers and the effect of iron on all-cause mortality in HUNT.Communications biology · 2022Pooled it
- Association between Anemia and Risk of Parkinson Disease.Behavioural neurology · 2021Pooled it
- Adult height, coronary heart disease and stroke: a multi-locus Mendelian randomization meta-analysis.International journal of epidemiology · 2016Pooled it
- A significant causal association between C-reactive protein levels and schizophrenia.Scientific reports · 2016Pooled it
- Evaluation of an association between plasma total homocysteine and schizophrenia by a Mendelian randomization analysis.BMC medical genetics · 2015Pooled it
- Meta-analyses of blood homocysteine levels for gender and genetic association studies of the MTHFR C677T polymorphism in schizophrenia.Schizophrenia bulletin · 2014Pooled it
- Genetic comorbidities in Parkinson's disease.Human molecular genetics · 2014Pooled it
- Trial
- Simulating vagus nerve stimulation through Basti therapy: A novel approach to anti-inflammatory treatment in Parkinson's disease model.Journal of Ayurveda and integrative medicine · 2026Review
- Trace Elements Dyshomeostasis and Toxic Metals Neurotoxicity in Neurodegenerative Diseases.Biological trace element research · 2026Review
- Reimagining the contribution of iron in Parkinson's disease.Neurobiology of disease · 2026Review
- Associations of genetic variants with gene expression factors reveal biological pathways underlying complex traits.American journal of human genetics · 2026Article
- Blood and cerebrospinal fluid metallomics uncover mercury, chromium, and iron alterations inJournal of Parkinson's disease · 2025Article
- Dietary Factors Affect Brain Iron Accumulation and Parkinson's Disease Risk.medRxiv : the preprint server for health sciences · 2025Article
- Nigrostriatal iron accumulation in the progression of Parkinson's disease.NPJ Parkinson's disease · 2025Article
- High correlation of quantitative susceptibility mapping and echo intensity measurements of nigral iron overload in Parkinson's disease.Journal of neural transmission (Vienna, Austria : 1996) · 2025Article
- In defence of ferroptosis.Signal transduction and targeted therapy · 2025Review
- Two sample Mendelian Randomisation using an outcome from a multilevel model of disease progression.European journal of epidemiology · 2024Article
- Iron homeostasis in older adults: balancing nutritional requirements and health risks.The journal of nutrition, health & aging · 2024Review
- Screening of key immuneZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2024Article
24 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
21 authors at 12 institutions in 5 countries.
Funding
Abstract
backgroundAlthough levels of iron are known to be increased in the brains of patients with Parkinson disease (PD), epidemiological evidence on a possible effect of iron blood levels on PD risk is inconclusive, with effects reported in opposite directions. Epidemiological studies suffer from problems of confounding and reverse causation, and mendelian randomization (MR) represents an alternative approach to provide unconfounded estimates of the effects of biomarkers on disease. We performed a MR study where genes known to modify iron levels were used as instruments to estimate the effect of iron on PD risk, based on estimates of the genetic effects on both iron and PD obtained from the largest sample meta-analyzed to date. METHODS AND
findingsWe used as instrumental variables three genetic variants influencing iron levels, HFE rs1800562, HFE rs1799945, and TMPRSS6 rs855791. Estimates of their effect on serum iron were based on a recent genome-wide meta-analysis of 21,567 individuals, while estimates of their effect on PD risk were obtained through meta-analysis of genome-wide and candidate gene studies with 20,809 PD cases and 88,892 controls. Separate MR estimates of the effect of iron on PD were obtained for each variant and pooled by meta-analysis. We investigated heterogeneity across the three estimates as an indication of possible pleiotropy and found no evidence of it. The combined MR estimate showed a statistically significant protective effect of iron, with a relative risk reduction for PD of 3% (95% CI 1%-6%; p = 0.001) per 10 µg/dl increase in serum iron.
conclusionsOur study suggests that increased iron levels are causally associated with a decreased risk of developing PD. Further studies are needed to understand the pathophysiological mechanism of action of serum iron on PD risk before recommendations can be made.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.