ArticleProceedings of the National Academy of Sciences of the United States of America2012
Brain structure in healthy adults is related to serum transferrin and the H63D polymorphism in the HFE gene.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
59 citing papers in PubMed, 2 syntheses or guidelines pooled it, 79 citations in OpenAlex.
- Abnormal Serum Iron-Status Indicator Changes in Amyotrophic Lateral Sclerosis (ALS) Patients: A Meta-Analysis.Frontiers in neurology · 2020Pooled it
- Integrative Review of Genetic Factors Influencing Neurodevelopmental Outcomes in Preterm Infants.Biological research for nursing · 2016Pooled it
- Effects of iron supplementation of low-birth-weight infants on cognition and behavior at 7 years: a randomized controlled trial.Pediatric research · 2018Trial
- A randomized, blinded, placebo-controlled trial of education and iron supplementation for mitigation of iron deficiency in regular blood donors.Transfusion · 2016Trial
- The strategies to reduce iron deficiency in blood donors randomized trial: design, enrolment and early retention.Vox sanguinis · 2015Trial
- Collection Series "Iron Homeostasis".International journal of molecular sciences · 2025Article
- Astronaut omics and the impact of space on the human body at scale.Nature communications · 2024Review
- Common Mutation in theStroke · 2023Article
- Association of Transferrin Gene Polymorphism with Cognitive Deficits and Psychiatric Symptoms in Patients with Chronic Schizophrenia.Journal of clinical medicine · 2022Article
- Polymorphism of Transferrin Gene Impacts the Mediating Effects of Psychotic Symptoms on the Relationship between Oxidative Stress and Cognition in Patients with Chronic Schizophrenia.Antioxidants (Basel, Switzerland) · 2022Article
- Iron-regulatory genes are associated with Neuroimaging measures in HIV infection.Brain imaging and behavior · 2020Article
- Association of blood donation with iron deficiency among adolescent and adult females in the United States: a nationally representative study.Transfusion · 2019Article
- Elevated risk for iron depletion in high-school age blood donors.Transfusion · 2019Article
- Deciphering the Iron Side of Stroke: Neurodegeneration at the Crossroads Between Iron Dyshomeostasis, Excitotoxicity, and Ferroptosis.Frontiers in neuroscience · 2019Review
- Fractional anisotropy of white matter, disability and blood iron parameters in multiple sclerosis.Metabolic brain disease · 2018Article
- Structural Neuroimaging of Anorexia Nervosa: Future Directions in the Quest for Mechanisms Underlying Dynamic Alterations.Biological psychiatry · 2018Review
- Reduced Cerebral White Matter Integrity Assessed by DTI in Cognitively Normal H63D-HFE Polymorphism Carriers.Journal of neuroimaging : official journal of the American Society of Neuroimaging · 2018Article
- Genetic Association of HLA Gene Variants with MRI Brain Structure in Alzheimer's Disease.Molecular neurobiology · 2017Article
- Post translational changes to α-synuclein control iron and dopamine trafficking; a concept for neuron vulnerability in Parkinson's disease.Molecular neurodegeneration · 2017Review
- 2016 proceedings of the National Heart, Lung, and Blood Institute's scientific priorities in pediatric transfusion medicine.Transfusion · 2017Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Control of iron homeostasis is essential for healthy central nervous system function: iron deficiency is associated with cognitive impairment, yet iron overload is thought to promote neurodegenerative diseases. Specific genetic markers have been previously identified that influence levels of transferrin, the protein that transports iron throughout the body, in the blood and brain. Here, we discovered that transferrin levels are related to detectable differences in the macro- and microstructure of the living brain. We collected brain MRI scans from 615 healthy young adult twins and siblings, of whom 574 were also scanned with diffusion tensor imaging at 4 Tesla. Fiber integrity was assessed by using the diffusion tensor imaging-based measure of fractional anisotropy. In bivariate genetic models based on monozygotic and dizygotic twins, we discovered that partially overlapping additive genetic factors influenced transferrin levels and brain microstructure. We also examined common variants in genes associated with transferrin levels, TF and HFE, and found that a commonly carried polymorphism (H63D at rs1799945) in the hemochromatotic HFE gene was associated with white matter fiber integrity. This gene has a well documented association with iron overload. Our statistical maps reveal previously unknown influences of the same gene on brain microstructure and transferrin levels. This discovery may shed light on the neural mechanisms by which iron affects cognition, neurodevelopment, and neurodegeneration.
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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.