Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis
Open accessAbstract
Variation in body iron is associated with or causes diseases, including anaemia and iron overload. Here, we analyse genetic association data on biochemical markers of iron status from 11 European-population studies, with replication in eight additional cohorts (total up to 48,972 subjects). We find 11 genome-wide-significant (P<5 × 10(-8)) loci, some including known iron-related genes (HFE, SLC40A1, TF, TFR2, TFRC, TMPRSS6) and others novel (ABO, ARNTL, FADS2, NAT2, TEX14). SNPs at ARNTL, TF, and TFR2 affect iron markers in HFE C282Y homozygotes at risk for hemochromatosis. There is substantial overlap between our iron loci and loci affecting erythrocyte and lipid phenotypes. These results will facilitate investigation of the roles of iron in disease.
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The three SNPs collectively explain approximately 3.8% of the variation in serum iron.
“collectively explain approximately 3.8% of the variation in serum iron [2,8].”
From Associations of genetically determined iron status across the phenome: A mendelian randomization study (2019) · cites this paper as [2]
The Results section ('SNP and gene associations'; page not available) reports that lead SNPs at eleven significant loci explained 3.4% of serum-iron variance in the replication cohorts. It supports the general point that SNPs explain some variation in serum iron, but not the attributed figure of approximately 3.8% for three SNPs. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThree genetic variants (rs1800562 and rs1799945 in HFE and rs855791 in TMPRSS6) associate with increased serum iron, ferritin, and transferrin saturation and decreased transferrin levels, serving as instruments for systemic iron status.
“3 genetic variants (rs1800562 and rs1799945 in the hemochromatosis gene [HFE] and rs855791 in the transmembrane protease serine 6 gene [TMPRSS6]) that associate with increased serum iron, ferritin, and transferrin saturation and decreased transferrin levels, thus serving as instruments for systemic iron status.”
From Associations of genetically determined iron status across the phenome: A mendelian randomization study (2019) · cites this paper as [2]
The Results section (page unavailable) identifies rs1800562, rs1799945 and rs855791 as lead SNPs in HFE and TMPRSS6. The Discussion (page unavailable) reports that these loci mainly affect serum iron and transferrin saturation, have smaller effects on ferritin, and also affect transferrin. Our copy does not establish the claimed increase in all three measures and decrease in transferrin for each of the three variants. (LLM, conf=0.82)
Experimental — accuracy not yet measuredThe Genetics of Iron Status Consortium GWAS on 48,972 European subjects identified the 3 SNPs rs1800562, rs1799945, and rs855791.
“A genome-wide association study (GWAS) performed by the Genetics of Iron Status Consortium on 48,972 European subjects (combined Discovery [N = 23,986] and Replication [N = 24,986] cohorts, 55% female) identified 3 such single-nucleotide polymorphisms (SNPs): rs1800562 and rs1799945 in the hemochromatosis (HFE) gene and rs855791 in the transmembrane protease serine 6 (TMPRSS6) gene [2,8,10].”
From Associations of genetically determined iron status across the phenome: A mendelian randomization study (2019) · cites this paper as [2]
The two HFE SNPs are in low linkage disequilibrium (LD r2 < 0.01) in combined European populations.
“The two SNPs in the HFE gene were in low linkage disequilibrium (LD r2 < 0.01) when considering combined European populations with the LDlink resource [2,17].”
From Associations of genetically determined iron status across the phenome: A mendelian randomization study (2019) · cites this paper as [2]
The Methods section on HFE C282Y homozygotes identifies rs1800562, but does not report linkage disequilibrium between two HFE SNPs. Searches for the SNP pair, LDlink, and the claimed r² threshold found no measurement for combined European populations in our copy. (LLM, conf=0.74)
Experimental — accuracy not yet measuredTMPRSS6 genetic variants modulate iron and hematologic traits in several genome-wide association studies, alter hepcidin levels in normal subjects and might confer susceptibility/resistance to iron deficiency, as observed in blood donors.
“TMPRSS6 genetic variants modulate iron and hematologic traits in several genome-wide association studies,58 alter hepcidin levels in normal subjects86 and might confer susceptibility/resistance to iron deficiency, as observed in blood donors.87”
From Iron metabolism and iron disorders revisited in the hepcidin era (2020) · cites this paper as [58]
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“6).”
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“The pathways involved are unknown, but iron homeostasis and lipid metabolism show overlap in the literature 32, 48, 49, 50, 51 as well as in our data.”
Scotet, V. (2003) · American Journal of Epidemiology · doi:10.1093/aje/kwg123 · Cited by 89 · cited 1× · see citing works
“Apart from age, sex and probably alcohol intake 63 , the focus has been on genetic modifiers but no candidate has been convincingly identified 64 .”
Pooled analysis of iron-related genes in Parkinson's disease: Association with transferrin
Rhodes, S. L., Buchanan, D. D., Ahmed, I., Taylor, K. D., Loriot, M., Sinsheimer, J. S., Bronstein, J. M., Elbaz, A., Mellick, G. D., Rotter, J. I., et al. (2013) · Neurobiology of Disease · doi:10.1016/j.nbd.2013.09.019 · Cited by 87 · cited 1× · see citing works
“…research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms information on genetic causes of variation can be used in Mendelian randomisation studies to test whether variation in iron status is a cause or consequence of disease 14, 15 .”
Genetic mechanisms and modifying factors in hereditary hemochromatosis
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“Apart from age, sex and probably alcohol intake 63 , the focus has been on genetic modifiers but no candidate has been convincingly identified 64 .”
Diurnal Rhythm rather than Dietary Iron Mediates Daily Hepcidin Variations
Schaap, C., Hendriks, J. C., Kortman, G. A. M., Klaver, S. M., Kroot, J. J., Laarakkers, C. M., Wiegerinck, E. T. G., Tjalsma, H., Janssen, M. C. H., & Swinkels, D. W. (2012) · Clinical Chemistry · doi:10.1373/clinchem.2012.194977 · Cited by 81 · see citing works
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“…significantly affect iron status, and compilation of genomic scores, will allow Mendelian randomisation studies on the multiple conditions associated with variation in iron load and help to clarify a potential causal role of iron in such conditions (e.g. Parkinson’s 14 or Alzheimer’s 66 diseases).”
Pichler, I., Minelli, C., Sanna, S., Tanaka, T., Schwienbacher, C., Naitza, S., Porcu, E., Pattaro, C., Busonero, F., Zanon, A., et al. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq552 · Cited by 76 · cited 2× · see citing works
“Four of these ( HFE , TF , TFR2 , TMPRSS6 ) were previously known to affect iron biomarker variation in the general population 18, 19 .”
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“Iron overload damages the liver and other organs in hereditary hemochromatosis 4, and in thalassemia patients with both transfusion and non-transfusion-related iron accumulation 5 .”
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“Notably, serum iron 16, 36 , liver iron 37 , hepcidin 38 , and TfR1 gene expression 39 all show circadian variation.”
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“Results are summarized in Supplementary Table 8.”
Traglia, M., Sala, C. F., Masciullo, C., Cverhova, V., Lori, F., Pistis, G., Bione, S., Gasparini, P., Ulivi, S., Ciullo, M., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007554 · Cited by 46 · cited 1× · see citing works
“These phenotypes show significant heritability in normal adults 16, 17 , and previous population-based studies have identified relevant SNPs and gene loci ( HFE , TF , TFR2 and TMPRSS6 18, 19 ) for iron status biomarkers.”
Self-citationTotal Mortality by Transferrin Saturation Levels: Two General Population Studies and a Metaanalysis
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“Variation in transferrin saturation, a biomarker of iron status, has been associated with mortality in patients with diabetes 12 and in the general population 13 .”
Diurnal cycle influences peripheral and brain iron levels in mice
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“Notably, serum iron 16, 36 , liver iron 37 , hepcidin 38 , and TfR1 gene expression 39 all show circadian variation.”
Influences of sleep and the circadian rhythm on iron-status indices
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“Notably, serum iron 16, 36 , liver iron 37 , hepcidin 38 , and TfR1 gene expression 39 all show circadian variation.”
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Mass Spectrometry Analysis of Hepcidin Peptides in Experimental Mouse Models
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“In mice, homozygosity for deletion of both Hfe and TfR2 greatly decreases hepcidin levels 59 and causes massive iron overload 60 .”
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“Since iron homeostasis involves a complex regulating network 23, 65 , it seems probable that any genetic effects on penetrance are either highly polygenic (in which case large genome-wide studies on HFE C282Y homozygotes will be needed) or result from rare variants which have not yet been examined…”
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“Another gene within the LD block, MTMR4 , deserves consideration because it changes SMAD phosphorylation, with possible effects on the BMP-SMAD pathway affecting control of hepcidin 34 .”
Total Mortality by Elevated Transferrin Saturation in Patients With Diabetes
Ellervik, C., Andersen, H. U., Tybjærg‐Hansen, A., Frandsen, M., Birgens, H., Nordestgaard, B. G., & Mandrup-Poulsen, T. R. (2013) · Diabetes Care · doi:10.2337/dc12-2032 · Cited by 17 · cited 1× · see citing works
“Variation in transferrin saturation, a biomarker of iron status, has been associated with mortality in patients with diabetes 12 and in the general population 13 .”
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Mendelian Randomization as an Approach to Assess Causality Using Observational Data
Sekula, P., Del Greco M, F., Pattaro, C., & Köttgen, A. (2016) · Journal of the American Society of Nephrology · doi:10.1681/asn.2016010098 · Cited by 2,351 · see citing works
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“Genome-wide association studies found overlapping associations for iron and lipid traits.(58) Adipocytes produce hepcidin in severe obesity(59) and hepcidin and gluconeogenesis are concomitantly upregulated in conditions of insulin-resistance.”
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New insights into iron deficiency and iron deficiency anemia
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Self-citationThe multifaceted role of iron in renal health and disease
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A role of PIEZO1 in iron metabolism in mice and humans
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“Genome-wide association studies (GWAS) have recently identified genes in addition to HFE that may be involved in iron overload (Benyamin et al., 2014).”
Keaton, J. M., Kamali, Z., Xie, T., Vaez, A., Williams, A., Goleva, S. B., Ani, A., Εvangelou, Ε., Hellwege, J. N., Yengo, L., et al. (2024) · Nature Genetics · doi:10.1038/s41588-024-01714-w · Cited by 232 · see citing works
“Genetic variation at TMPRSS6 is also associated with biomarkers of iron overload 27 .”
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“have recently been reported, some including known iron-related genes and other novel genes (11, 12).”
BackgroundInherited iron overload disorders
Piperno, A., Pelucchi, S., & Mariani, R. (2020) · Translational Gastroenterology and Hepatology · doi:10.21037/tgh.2019.11.15 · Cited by 151 · see citing works
“Cys282Tyr homozygotes have given uncertain results (105-110).”
Iron and restless legs syndrome: treatment, genetics and pathophysiology
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“There was a report in which individuals with RLS demonstrate allelic similarities on chromosome 12q (where the nNOS gene is located) [42], but these data have not been reproduced in specific studies [43] or GWAS analyses.”
BackgroundInfluentialSelf-citationGenetics, genetic testing, and management of hemochromatosis: 15 years since hepcidin
Pietrangelo, A. (2015) · Gastroenterology · doi:10.1053/j.gastro.2015.06.045 · Cited by 136 · see citing works
Iron Status and Risk of Stroke: A Mendelian Randomization Study
Gill, D., Monori, G., Tzoulaki, I., & Dehghan, A. (2018) · Stroke · doi:10.1161/strokeaha.118.022701 · Cited by 110 · see citing works
A decade in psychiatric GWAS research
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“All genetic associations were based on GWAS of European ancestry samples.”
BackgroundInfluentialPathophysiological consequences and benefits of HFE mutations: 20 years of research
Hollerer, I., Bachmann, A., & Muckenthaler, M. U. (2017) · Haematologica · doi:10.3324/haematol.2016.160432 · Cited by 80 · see citing works
“in transmembrane protease, serine 6 (TMPRSS6)(87) and in the vicinity of the genes FADS2, NAT2, ABO and TEX14.(86) SNPs in transferrin (TF),(86,88) transferrin receptor 2 (TFR2),(86) bone morphogenetic protein 2 (BMP2),(89) aryl hydrocarbon receptor nuclear translocator-like protein 1 (ARNTL),(20) glyceronephosphate O…”
BackgroundGill, D., Benyamin, B., Moore, L. S. P., Monori, G., Zhou, A., Koskeridis, F., Evangelou, E., Laffan, M., Walker, A. P., Tsilidis, K. K., et al. (2019) · PLOS Medicine · doi:10.1371/journal.pmed.1002833 · Cited by 63 · see citing works
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Genetic regulation of post-translational modification of two distinct proteins
Landini, A., Trbojević‐Akmačić, I., Navarro, P., Tsepilov, Y. A., Sharapov, S., Vučković, F., Polašek, O., Hayward, C., Pribić, T., Vilaj, M. Ć., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-29189-5 · Cited by 39 · see citing works
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“Like-wise, the index variant in the DUOX2 (cadmium) locus known from GWASs of iron status biomarkers 60,83,96 , was associated with iron de fi ciency anemia.”
Iron status and the risk of sepsis and severe COVID-19: a two-sample Mendelian randomization study
Mohus, R. M., Flatby, H., Liyanarachi, K. V., DeWan, A. T., Solligård, E., Damås, J. K., Åsvold, B. O., Gustad, L. T., & Rogne, T. (2022) · Scientific Reports · doi:10.1038/s41598-022-20679-6 · Cited by 28 · see citing works
“An MR-study using iron related SNPs identified in the Genetics of Iron Status-consortia (38) found evidence that higher serum-iron, TSAT and ferritin were related to increased risk of sepsis (21).”
MethodSi, S., Li, J., Tewara, M. A., Li, H., Liu, X., Li, Y., Chen, X., Liu, C., Yuan, T., Li, W., et al. (2021) · British Journal of Cancer · doi:10.1038/s41416-021-01576-7 · Cited by 19 · see citing works
Strong, M. D., Hart, M. D., Tang, T. Z., Ojo, B. A., Wu, L., Nacke, M. R., Agidew, W. T., Hwang, H. J., Hoyt, P. R., Bettaieb, A., et al. (2020) · The FASEB Journal · doi:10.1096/fj.202000772r · Cited by 14 · see citing works
Tian, T., Xiao, F., Li, H., Ding, D., Wei, D., Hou, G., Zhao, L., Yang, Y., Yang, Y., & Zhou, W. (2021) · Annals of Translational Medicine · doi:10.21037/atm-21-4608 · Cited by 11 · see citing works
“The genetic data of serum iron status were derived from a GWAS consisting of 48,972 European individuals (13).”
MethodInfluentialToivonen, J., Allara, E., FinnGen, Castrén, J., Angelantonio, E. D., & Arvas, M. (2023) · Vox Sanguinis · doi:10.1111/vox.13564 · Cited by 7 · see citing works
“…SNP has not been previously reported to be associated with IDA, in the 1-Mb area around RNF43, ferritin associations have been reported in genes MRPS23 [27] in Dutch blood donor population, MTMR4 in the UK, Danish and Icelandic population [17] and TEX14 in European populations [28].”
BackgroundTimmer, T. C., Tanck, M. W. T., Penkett, C. J., Stirrups, K. E., Gleadall, N., de Kort, W. L. A. M., van der Schoot, C. E., & van den Hurk, K. (2021) · Vox Sanguinis · doi:10.1111/vox.13066 · Cited by 7 · see citing works
Serum iron status and the risk of lung cancer: a two-sample Mendelian-randomization study
Feng, X., Zhao, T., Liu, X., Liu, Y., & Gao, Y. (2023) · Journal of Thoracic Disease · doi:10.21037/jtd-23-1645 · Cited by 7 · see citing works
“Before the genome-wide analyses were performed, adjustments for population characteristics were made to ensure the consistency of the analysis (14).”
Qin, H., Zeng, W., & Lou, Y.-F. (2022) · Medicine · doi:10.1097/md.0000000000029879 · Cited by 6 · see citing works
“Single-nucleotide polymorphisms (SNPs) for iron status were obtained from the GWAS summary performed by the GIS consortium,[9] which combined data from 11 discovery and 8 replication cohorts encompassing 48,972 individuals of European ancestry.”
MethodInfluentialTang, Z., Shen, M., Chen, X., & Liu, Y. (2021) · Pediatric Allergy and Immunology · doi:10.1111/pai.13565 · Cited by 3 · see citing works
Moksnes, M. R., Hansen, A. F., Graham, S. E., Taliun, S. A. G., Wu, K.-H., Zhou, W., Thorstensen, K., Fritsche, L. G., Gill, D., Mason, A. M., et al. (2021) · medRxiv · doi:10.1101/2021.09.20.21262960 · Cited by 3 · see citing works
Effects of genetically determined mineral status on life expectancy: a Mendelian randomization study
Fang, H., Chen, W., Jin, A., Wang, M., Yan, H., Xiang, X., & Pan, Y. (2023) · Chinese Medical Journal · doi:10.1097/cm9.0000000000002436 · Cited by 1 · see citing works
“[2 The magnesium-related genetic variation data were derived from the European ancestry GWAS ( n = 15,366) from the International Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, and these single-nucleotide polymorphisms (SNPs) were fi [3] blood copper, , and…”
Association of dietary nutrient intake with type 2 diabetes: A Mendelian randomization study
Kang, R., Guo, D., Wang, J., & Xie, Z. (2024) · Medicine · doi:10.1097/md.0000000000038090 · Cited by 1 · see citing works
“…acid (DHA), docosapentaenoic acid (DPA), dihomo-gamma-linolenic acid (DGLA), eicosapentaenoic acid (EPA), gamma-linolenic acid (GLA), and linoleic acid (LA) [32,33] Metal elements identified include calcium (Ca), copper (Cu), [34] iron (Fe), [35] magnesium (Mg), selenium (Se), [34] zinc (Zn).”
BackgroundExploring genetic association of systemic iron status and risk with incidence of diabetic neuropathy
Yu, X., Jin, T., Zhu, L., Guo, S., Deng, B., & Cheng, Y. (2024) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-024-01418-5 · Cited by 1 · see citing works
“We derived summary information of SNPs associated with iron status biomarkers from a prior meta-analysis of GWAS by the Genetics of Iron Status Consortium, involving 48,972 individuals of European descent from 19 cohorts [19].”
MethodWilman, H., Parisinos, C. A., Kelly, M., Neubauer, S., Thomas, E. L., Bell, J. D., Banerjee, R., & Yaghootkar, H. (2019) · Journal of Hepatology · doi:10.1016/s0618-8278(19)30236-1 · Cited by 1 · see citing works
Hou, C., Hou, Q., Xie, X., Wang, H.-F., Chen, Y., Lu, T., Wu, Q., Liang, Y., Hu, Y., & Mao, Y. (2020) · Research Square · doi:10.21203/rs.3.rs-57485/v1
“Selection of instrumental variables Instrumental variables of the MR analysis which were strongly signi cant on iron status (P < 5 × 10-8) were selected from the GIS consortium (Table 1-4) [14].”
BackgroundMethodShen, J., Xu, L., Wu, X., & Ding, Y. (2024) · Reproductive Sciences · doi:10.1007/s43032-024-01476-0
“This finding was subsequently validated in an additional 8 populations, resulting in a total sample size of 48,972 individuals [20].”
Exploring the Links Between Micronutrients and Cardiac Traits: Roles of Vitamins A1, B9, and D
Liu, L., Cheng, Y., Yan, S., & Zhou, J. (2025) · The Journal of Gene Medicine · doi:10.1002/jgm.70022
- Authors
- Benyamin, B., Esko, T., Ried, J. S., Radhakrishnan, A., Vermeulen, S. H., Traglia, M., Gögele, M., Anderson, D., Broer, L., Podmore, C., Luan, J., Kutalik, Z., Sanna, S., van der Meer, P., Tanaka, T., Wang, F., Westra, H.-J., Franke, L., Mihailov, E., Milani, L., Hälldin, J., Winkelmann, J., Meitinger, T., Thiery, J., Peters, A., Waldenberger, M., Rendon, A., Jolley, J., Sambrook, J., Kiemeney, L. A., Sweep, F. C., Sala, C. F., Schwienbacher, C., Pichler, I., Hui, J., Demirkan, A., Isaacs, A., Amin, N., Steri, M., Waeber, G., Verweij, N., Powell, J. E., Nyholt, D. R., Heath, A. C., Madden, P. A. F., Visscher, P. M., Wright, M. J., Montgomery, G. W., Martin, N. G., Hernandez, D., Bandinelli, S., van der Harst, P., Uda, M., Vollenweider, P., Scott, R. A., Langenberg, C., Wareham, N. J., InterAct Consortium, van Duijn, C., Beilby, J., Pramstaller, P. P., Hicks, A. A., Ouwehand, W. H., Oexle, K., Gieger, C., Metspalu, A., Camaschella, C., Toniolo, D., Swinkels, D. W., & Whitfield, J. B.
- Affiliations
- The University of Queensland (AU)
- Helmholtz Munich (DE)
- University of Cambridge (GB)
- Radboud University Medical Center (NL)
- IRCCS Materno Infantile Burlo Garofolo (IT)
- Eurac Research (IT)
- The Kids Research Institute Australia (AU)
- Erasmus MC (NL)
- Institute of Genetic and Biomedical Research (IT)
- National Institute on Aging (US)
- Zhejiang University (CN)
- University Medical Center Groningen (NL)
- University of Tartu (EE)
- TUM Klinikum (DE)
- University Hospital Leipzig (DE)
- NHS Blood and Transplant (GB)
- IRCCS Ospedale San Raffaele (IT)
- The University of Western Australia (AU)
- Centre Hospitalier Universitaire Vaudois (CH)
- QIMR Berghofer Medical Research Institute (AU)
- Washington University in St. Louis (US)
- National Institutes of Health (US)
- Azienda Sanitaria di Firenze (IT)
- Vita-Salute San Raffaele University (IT)
- Corresponding author
- Benyamin, Beben
- Whitfield, John B.
- ORCID
- Benyamin, Beben
- Radhakrishnan, Aparna
- Vermeulen, Sita H.
- Traglia, Michela
- Gögele, Martin
- Anderson, Denise
- Broer, Linda
- Podmore, Clara
- Luan, Jian’an
- Sanna, Serena
- Tanaka, Toshiko
- Wang, Fudi
- Westra, Harm-Jan
- Franke, Lude
- Milani, Lili
- Winkelmann, Juliane
- Meitinger, Thomas
- Thiery, Joachim
- Peters, Annette
- Rendon, Augusto
- Kiemeney, Lambertus A.
- Sweep, Fred C.
- Sala, Cinzia F.
- Pichler, Irene
- Hui, Jennie
- Isaacs, Aaron
- Amin, Najaf
- Steri, Maristella
- Waeber, Gérard
- Verweij, Niek
- Powell, Joseph E.
- Nyholt, Dale R.
- Heath, Andrew C.
- Madden, Pamela A. F.
- Visscher, Peter M.
- Wright, Margaret J.
- Montgomery, Grant W.
- Martin, Nicholas G.
- Hernandez, Dena
- Bandinelli, Stefania
- Uda, Manuela
- Langenberg, Claudia
- Wareham, Nicholas J.
- Beilby, John
- Pramstaller, Peter P.
- Hicks, Andrew A.
- Ouwehand, Willem H.
- Oexle, Konrad
- Gieger, Christian
- Metspalu, Andres
- Camaschella, Clara
- Toniolo, Daniela
- Swinkels, Dorine W.
- Whitfield, John B.
- Venue
- Nature Communications
- Published
- 2014-10-29
- Volume
- 5
- Issue
- 1
- Pages
- 4926-4926
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC4215164
- OpenAlex
- W1498265623
- Cited by
- 30
- References
- 70
- Citations by year
- 2025: 1 · 2024: 5 · 2023: 3 · 2022: 5 · 2021: 5 · 2020: 4 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 1 · 2015: 1
- FWCI
- 0.95
- Type
- journal article
- Language
- en
- Update notices
- correction (2015-03-30)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Communications (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, cc-by)
- PubMed Central (acceptedVersion)
- QUT ePrints (Queensland University of Technology) (submittedVersion)
- IRIS (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- RePEc: Research Papers in Economics (submittedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Site cant be reached (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion, other-oa)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Faculty of Health; Institute of Health and Biomedical Innovation
- Apollo
- Funders
- Wellcome Trust (097451/Z/11/Z)
- National Institute for Health and Care Research (NF-SI-0510-10214, RP-PG-0310-1002, NF-SI-0513-10151, NF-SI-0512-10135)
- British Heart Foundation (RG/09/012/28096)
- National Institutes of Health
- Medical Research Council (MC_UU_12015/1)
- National Health and Medical Research Council (552498)
- National Institute on Alcohol Abuse and Alcoholism (R01AA014041)
- National Institute of Biomedical Imaging and Bioengineering (U54EB020403)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Keywords
- iron homeostasis, hemochromatosis, C282Y mutation, genetic association, iron status biomarkers, iron deficiency, anemia, iron overload, Bmal1, transferrin, transferrin receptor 2, SLC40A1, FADS2, NAT2, lipid phenotypes, European populations
- MeSH terms
- Adult, Chromosomes, Human, Pair 7, Ferritins, Gene Expression Regulation, Hemochromatosis, Homeostasis, Humans, Iron, Lipids, Phenotype, Risk Factors, Transferrin, Reproducibility of Results, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Genetic Loci, Genetic Association Studies
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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