ArticleJournal of hepatology2019
Genetic studies of abdominal MRI data identify genes regulating hepcidin as major determinants of liver iron concentration.
Article in Journal of hepatology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 31 citations in OpenAlex.
- Unravelling genetic susceptibility and causal factors in liver health using MRI quantification of inflammation, fat and iron in the liver.Human genomics · 2026Article
- Serum metabolites characterize hepatic phenotypes and reveal shared pathways: results from population-based imaging.Molecular medicine (Cambridge, Mass.) · 2025Article
- An optimized instrument variable selection approach to improve causality estimation in association studies.Scientific reports · 2024Article
- Multi-organ imaging-derived polygenic indexes for brain and body health.medRxiv : the preprint server for health sciences · 2024Article
- Using Mendelian Randomization to Study the Role of Iron in Health and Disease.International journal of molecular sciences · 2023Review
- Inherited basis of visceral, abdominal subcutaneous and gluteofemoral fat depots.Nature communications · 2022Article
- A rare genetic variant in the manganese transporter SLC30A10 and elevated liver enzymes in the general population.Hepatology international · 2022Article
- LncXIST Facilitates Iron Overload and Iron Overload-Induced Islet Beta Cell Injury in Type 2 Diabetes through miR-130a-3p/ALK2 Axis.Computational intelligence and neuroscience · 2022Article
- Distribution and Associated Factors of Hepatic Iron-A Population-Based Imaging Study.Metabolites · 2021Article
- MRI-Based Iron Phenotyping and Patient Selection for Next-Generation Sequencing of Non-Homeostatic Iron Regulator Hemochromatosis Genes.Hepatology (Baltimore, Md.) · 2021Article
- Genetic Support of A Causal Relationship Between Iron Status and Type 2 Diabetes: A Mendelian Randomization Study.The Journal of clinical endocrinology and metabolism · 2021Article
- Ethnic Differences in Iron Status.Advances in nutrition (Bethesda, Md.) · 2021Review
- Article
- Whole Genome Interpretation for a Family of Five.Frontiers in genetics · 2021Article
- Multiparametric MR mapping in clinical decision-making for diffuse liver disease.Abdominal radiology (New York) · 2020Review
- Genome-wide and Mendelian randomisation studies of liver MRI yield insights into the pathogenesis of steatohepatitis.Journal of hepatology · 2020Article
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Authors and funding
15 authors at 8 institutions in 3 countries.
Funding
Abstract
BACKGROUND &
aimsExcess liver iron content is common and is linked to the risk of hepatic and extrahepatic diseases. We aimed to identify genetic variants influencing liver iron content and use genetics to understand its link to other traits and diseases.
methodsFirst, we performed a genome-wide association study (GWAS) in 8,289 individuals from UK Biobank, whose liver iron level had been quantified by magnetic resonance imaging, before validating our findings in an independent cohort (n = 1,513 from IMI DIRECT). Second, we used Mendelian randomisation to test the causal effects of 25 predominantly metabolic traits on liver iron content. Third, we tested phenome-wide associations between liver iron variants and 770 traits and disease outcomes.
resultsWe identified 3 independent genetic variants (rs1800562 [C282Y] and rs1799945 [H63D] in HFE and rs855791 [V736A] in TMPRSS6) associated with liver iron content that reached the GWAS significance threshold (p <5 × 10
conclusionOur study provides genetic evidence that mechanisms underlying higher liver iron content are likely systemic rather than organ specific, that higher central obesity is causally associated with higher liver iron, and that liver iron shares common aetiology with multiple metabolic and non-metabolic diseases. LAY SUMMARY: Excess liver iron content is common and is associated with liver diseases and metabolic diseases including diabetes, high blood pressure, and heart disease. We identified 3 genetic variants that are linked to an increased risk of developing higher liver iron content. We show that the same genetic variants are linked to higher risk of many diseases, but they may also be associated with some health advantages. Finally, we use genetic variants associated with waist-to-hip ratio as a tool to show that central obesity is causally associated with increased liver iron content.
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