ArticleNature communications2021
Epigenome-wide association study of serum urate reveals insights into urate co-regulation and the SLC2A9 locus.
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In one paragraph
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
2.6field-weighted citation impact, top 9% of its field
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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.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Epigenome-wide meta-analysis identifies DNA methylation biomarkers associated with diabetic kidney disease.Nature communications · 2022Pooled it
- A potential association of SLC2A9 variant rs7442295 with uric acid at baseline and in interaction with iloperidone.The pharmacogenomics journal · 2026Trial
- Multi-omics insights into uric acid metabolism in cardiometabolic disease: from genetics to metabolomics.Biomedical journal · 2026Review
- [Association of metabolic syndrome and its components with gout: an analysis based on a large-scale health survey database].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2026Article
- Perceptions About Asymptomatic Hyperuricemia and Views About Urate-Lowering Therapy in People With Asymptomatic Hyperuricemia.Arthritis care & research · 2026Article
- Advances in post-translational and epigenetic modification of hyperuricemia-to-gout progression: mechanisms and therapeutic targets.Frontiers in cell and developmental biology · 2026Review
- A review of the evidence for a protective role of uric acid in Parkinson's disease.NPJ Parkinson's disease · 2025Review
- Sex-specific DNA methylation associations with circulating urate levels and BCG-induced urate changes.Communications medicine · 2025Article
- Epigenetic isoforms (DNMT3A/3B and HDAC3/7) potential predictors of endothelial dysfunction and subclinical atherosclerosis.Molecular biology reports · 2025Review
- Alteration in epigenetic profile in subclinical atherosclerosis and in high uric acid.Scientific reports · 2025Article
- The causal relationship between emotions and osteoarthritis: A bidirectional Mendelian randomization study.Medicine · 2025Article
- Epigenetic programming reshapes innate immune memory: decoding the molecular imprint of gouty inflammation.Frontiers in pharmacology · 2025Review
- Downregulation of type I interferon signalling pathway by urate in primary human PBMCs.Immunology · 2025Article
- Comprehensive Treatment of Gout with Traditional Chinese Medicine: A Modern Pathophysiological Perspective.International journal of general medicine · 2025Review
- The pathogenesis of gout: molecular insights from genetic, epigenomic and transcriptomic studies.Nature reviews. Rheumatology · 2024Review
- metaGWASmanager: a toolbox for an automated workflow from phenotypes to meta-analysis in GWAS consortia.Bioinformatics (Oxford, England) · 2024Article
- Epigenetic and Metabolic Regulation of Macrophages during Gout.Gout, urate, and crystal deposition disease · 2023Article
- A comparison of the genes and genesets identified by GWAS and EWAS of fifteen complex traits.Nature communications · 2022Article
- Epigenomic and Other Evidence for Cannabis-Induced Aging Contextualized in a Synthetic Epidemiologic Overview of Cannabinoid-Related Teratogenesis and Cannabinoid-Related Carcinogenesis.International journal of environmental research and public health · 2022Review
Corrections and comments
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Authors and funding
105 authors at 20 institutions in 13 countries.
Adrienne Tin *Department of Medicine, University of Mississippi Medical Center, Jackson, 39216, MS, USA. atin@umc.edu.ORCID http://orcid.org/0000-0002-4207-5866
Pascal Schlosser *Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-8460-0462
Pamela R Matias-GarciaResearch Unit Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, D-85764, Bavaria, Germany.
Chris H L ThioDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.ORCID http://orcid.org/0000-0003-2623-7172
Roby JoehanesFramingham Heart Study, Framingham, MA, USA.
Hongbo LiuDepartment of Medicine and Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, 19104, PA, USA.ORCID http://orcid.org/0000-0002-0733-8616
Zhi YuProgram in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-4810-3474
Antoine WeihsDepartment of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.ORCID http://orcid.org/0000-0002-7113-0027
Anselm HoppmannInstitute of Genetic Epidemiology, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany.
Franziska Grundner-CulemannInstitute of Genetic Epidemiology, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0000-0001-9649-281X
Josine L MinMRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.ORCID http://orcid.org/0000-0003-4456-9824
Victoria L Halperin KuhnsDepartment of Physiology, University of Maryland School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-6348-7931
Adebowale A AdeyemoCenter for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-3105-3231
Charles AgyemangDepartment of Public and Occupational Health, Amsterdam Public Health Research Institute, Amsterdam University Medical Centers, University of Amsterdam, 1105 AZ, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0002-3882-7295
Johan ÄrnlövDepartment of Neurobiology, Care Sciences and Society (NVS), Family Medicine and Primary Care Unit, Karolinska Institutet, Huddinge, Sweden.
Nasir A AzizPopulation Health Sciences, German Centre for Neurodegenerative Diseases (DZNE), Bonn, Germany.ORCID http://orcid.org/0000-0001-6184-458X
Andrea BaccarelliLaboratory of Environmental Precision Health, Mailman School of Public Health, Columbia University, New York, NY, USA.ORCID http://orcid.org/0000-0002-3436-0640
Murielle BochudCenter for Primary Care and Public Health (Unisanté), University of Lausanne, Lausanne, Switzerland.ORCID http://orcid.org/0000-0002-5727-0218
Hermann BrennerGerman Cancer Research Center (DKFZ), Division of Clinical Epidemiology and Aging Research, Heidelberg, Germany.
Jan BresslerHuman Genetics Center, Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, 77030, TX, USA.ORCID http://orcid.org/0000-0001-6578-4772
Monique M B BretelerPopulation Health Sciences, German Centre for Neurodegenerative Diseases (DZNE), Bonn, Germany.ORCID http://orcid.org/0000-0002-0626-9305
Cristian CarmeliCenter for Primary Care and Public Health (Unisanté), University of Lausanne, Lausanne, Switzerland.ORCID http://orcid.org/0000-0002-1463-4587
Layal ChakerDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Josef CoreshDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-4598-0669
Tanguy CorreCenter for Primary Care and Public Health (Unisanté), University of Lausanne, Lausanne, Switzerland.
Adolfo CorreaDepartment of Medicine, University of Mississippi Medical Center, Jackson, 39216, MS, USA.ORCID http://orcid.org/0000-0002-9501-600X
Simon R CoxLothian Birth Cohorts Group, Department of Psychology, The University of Edinburgh, 7 George Square, Edinburgh, EH8 9JZ, UK.ORCID http://orcid.org/0000-0003-4036-3642
Graciela E DelgadoVth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Kai-Uwe EckardtDepartment of Nephrology and Hypertension, University of Erlangen-Nürnberg, Erlangen, Germany.ORCID http://orcid.org/0000-0003-3823-0920
Arif B EkiciInstitute of Human Genetics, Friedrich-Alexander-UniversitätErlangen-Nürnberg, 91054, Erlangen, Germany.ORCID http://orcid.org/0000-0001-6099-7066
Karlhans EndlichDepartment of Anatomy and Cell Biology, University Medicine Greifswald, Greifswald, Germany.ORCID http://orcid.org/0000-0001-6052-6061
James S FloydDepartment of Medicine, University of Washington, Seattle, 98101, WA, USA.
Eliza FraszczykDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Xu GaoLaboratory of Environmental Precision Health, Mailman School of Public Health, Columbia University, New York, NY, USA.ORCID http://orcid.org/0000-0001-6506-6084
Xīn GàoGerman Cancer Research Center (DKFZ), Division of Clinical Epidemiology and Aging Research, Heidelberg, Germany.ORCID http://orcid.org/0000-0003-0108-6961
Allan C GelberDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.ORCID http://orcid.org/0000-0001-8463-311X
Mohsen GhanbariDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.ORCID http://orcid.org/0000-0002-9476-7143
Sahar GhasemiDepartment of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
Christian GiegerResearch Unit Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, D-85764, Bavaria, Germany.ORCID http://orcid.org/0000-0001-6986-9554
Philip GreenlandDepartment of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Megan L GroveHuman Genetics Center, Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, 77030, TX, USA.
Sarah E HarrisLothian Birth Cohorts Group, Department of Psychology, The University of Edinburgh, 7 George Square, Edinburgh, EH8 9JZ, UK.ORCID http://orcid.org/0000-0002-4941-5106
Gibran HemaniMRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.ORCID http://orcid.org/0000-0003-0920-1055
Peter HennemanDepartment of Clinical Genetics, Amsterdam Reproduction & Development Research Institute, Amsterdam University Medical Centres, University of Amsterdam, Amsterdam, the Netherlands.
Christian HerderInstitute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.ORCID http://orcid.org/0000-0002-2050-093X
Steve HorvathDepartment of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, 90095, CA, USA.ORCID http://orcid.org/0000-0002-4110-3589
Lifang HouDepartment of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Mikko A HurmeDepartment of Microbiology and Immunology, Faculty of Medicine and Health Technology, Tampere University, Tampere, 33014, Finland.
Shih-Jen HwangFramingham Heart Study, Framingham, MA, USA.
Sharon L R KardiaDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, 48109, MI, USA.
Silva KaselaEstonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
Marcus E KleberVth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.ORCID http://orcid.org/0000-0003-0663-7275
Wolfgang KoenigDeutsches Herzzentrum München, Technische Universität München, Munich, Germany.ORCID http://orcid.org/0000-0002-2064-9603
Jaspal S KoonerNational Heart and Lung Institute, Imperial College London, London, UK.
Florian KronenbergInstitute of Genetic Epidemiology, Medical University of Innsbruck, Innsbruck, Austria.ORCID http://orcid.org/0000-0003-2229-1120
Brigitte KühnelResearch Unit Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, D-85764, Bavaria, Germany.
Christine Ladd-AcostaDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Terho LehtimäkiDepartment of Clinical Chemistry, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.ORCID http://orcid.org/0000-0002-2555-4427
Lars LindDepartment of Medical Sciences, Uppsala University, Uppsala, Sweden.
Dan LiuPopulation Health Sciences, German Centre for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Donald M Lloyd-JonesDepartment of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Stefan LorkowskiInstitute of Nutritional Sciences, Friedrich Schiller University Jena, Jena, Germany.ORCID http://orcid.org/0000-0002-9649-840X
Ake T LuDepartment of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, 90095, CA, USA.ORCID http://orcid.org/0000-0002-2866-7961
Riccardo E MarioniCentre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XU, UK.
Winfried MärzVth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Daniel L McCartneyCentre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XU, UK.ORCID http://orcid.org/0000-0003-3242-0360
Karlijn A C MeeksCenter for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-3032-405X
Lili MilaniEstonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.ORCID http://orcid.org/0000-0002-5323-3102
Pashupati P MishraDepartment of Clinical Chemistry, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Matthias NauckDZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany.ORCID http://orcid.org/0000-0002-6678-7964
Christoph NowakDepartment of Neurobiology, Care Sciences and Society (NVS), Family Medicine and Primary Care Unit, Karolinska Institutet, Huddinge, Sweden.ORCID http://orcid.org/0000-0001-8435-3978
Annette PetersInstitute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, D-85764, Bavaria, Germany.ORCID http://orcid.org/0000-0001-6645-0985
Holger ProkischInstitute of Human Genetics, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.ORCID http://orcid.org/0000-0003-2379-6286
Bruce M PsatyDepartment of Medicine, University of Washington, Seattle, 98101, WA, USA.ORCID http://orcid.org/0000-0002-7278-2190
Olli T RaitakariResearch Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
Scott M RatliffDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, 48109, MI, USA.
Alex P ReinerDepartment of Epidemiology, University of Washington, Seattle, 98101, WA, USA.ORCID http://orcid.org/0000-0002-1427-4470
Ben SchöttkerGerman Cancer Research Center (DKFZ), Division of Clinical Epidemiology and Aging Research, Heidelberg, Germany.ORCID http://orcid.org/0000-0002-1217-4521
Joel SchwartzDepartment of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Sanaz SedaghatDivision of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
Jennifer A SmithDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, 48109, MI, USA.ORCID http://orcid.org/0000-0002-3575-5468
Nona SotoodehniaCardiovascular Health Research Unit, University of Washington, Seattle, 98101, WA, USA.
Hannah R StockerGerman Cancer Research Center (DKFZ), Division of Clinical Epidemiology and Aging Research, Heidelberg, Germany.ORCID http://orcid.org/0000-0001-5281-2455
Silvia StringhiniCenter for Primary Care and Public Health (Unisanté), University of Lausanne, Lausanne, Switzerland.ORCID http://orcid.org/0000-0002-4387-8943
Johan SundströmDepartment of Medical Sciences, Uppsala University, Uppsala, Sweden.ORCID http://orcid.org/0000-0003-2247-8454
Brenton R SwensonCardiovascular Health Research Unit, University of Washington, Seattle, 98101, WA, USA.
Joyce B J van MeursDepartment of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.
Jana V van Vliet-OstaptchoukDepartment of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.ORCID http://orcid.org/0000-0002-7943-3153
Andrea VenemaDepartment of Clinical Genetics, Amsterdam Reproduction & Development Research Institute, Amsterdam University Medical Centres, University of Amsterdam, Amsterdam, the Netherlands.
Uwe VölkerDZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany.ORCID http://orcid.org/0000-0002-5689-3448
Juliane WinkelmannInstitute of Human Genetics, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
Bruce H R WolffenbuttelDepartment of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.ORCID http://orcid.org/0000-0001-9262-6921
Wei ZhaoDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, 48109, MI, USA.ORCID http://orcid.org/0000-0001-7388-0692
Yinan ZhengDepartment of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID http://orcid.org/0000-0002-2006-7320
Estonian Biobank Research Team
Genetics of DNA Methylation Consortium
Marie LohLee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.ORCID http://orcid.org/0000-0003-3626-8466
Harold SniederDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.ORCID http://orcid.org/0000-0003-1949-2298
Melanie WaldenbergerResearch Unit Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, D-85764, Bavaria, Germany.ORCID http://orcid.org/0000-0003-0583-5093
Daniel LevyFramingham Heart Study, Framingham, MA, USA.ORCID http://orcid.org/0000-0003-1843-8724
Shreeram AkileshDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0003-3152-7991
Owen M WoodwardDepartment of Physiology, University of Maryland School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0001-9514-2180
Katalin SusztakDepartment of Medicine and Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, 19104, PA, USA.ORCID http://orcid.org/0000-0002-1005-3726
Alexander TeumerDZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany.ORCID http://orcid.org/0000-0002-8309-094X
Anna KöttgenDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. anna.koettgen@uniklinik-freiburg.de.ORCID http://orcid.org/0000-0002-4671-3714
Johns Hopkins University · USUniversity of Washington · USGerman Cancer Research Center · DEHelmholtz Zentrum München · DEUniversitätsmedizin Greifswald · DEUniversity Medical Center Groningen · NLNational Institutes of Health · USNorthwestern University · USUniversity of Michigan · USCentre universitaire de médecine générale et santé publique, Lausanne · CHErasmus MC · NLTampere University · FIEdinburgh Cancer Research · GBFriedrich-Alexander-Universität Erlangen-Nürnberg · DEHeidelberg University · DEThe University of Texas Health Science Center at Houston · USTUM Klinikum · DEUniversity of Amsterdam · NLUniversity of Bonn · DEUniversity of Bristol · GB
Funding
CHARGE Consortium: Omics Discovery for CVD and Aging PhenotypesR01HL105756 · NHLBI · UNIVERSITY OF WASHINGTON · PI Bruce M Psaty, NICHOLAS L SMITH · 2011 to 2026
$9.5MMolecular Mechanisms of Uric Acid HomeostasisR01DK114091 · NIDDK · UNIVERSITY OF MARYLAND BALTIMORE · PI WOODWARD, OWEN M · 2017 to 2020
$1.4MMedical Research Council MC_UU_00011/5NHLBI NIH HHS R01 HL105756NIDDK NIH HHS R01 DK114091Wellcome Trust 212945/Z/18/Z
Abstract
Elevated serum urate levels, a complex trait and major risk factor for incident gout, are correlated with cardiometabolic traits via incompletely understood mechanisms. DNA methylation in whole blood captures genetic and environmental influences and is assessed in transethnic meta-analysis of epigenome-wide association studies (EWAS) of serum urate (discovery, n = 12,474, replication, n = 5522). The 100 replicated, epigenome-wide significant (p < 1.1E-7) CpGs explain 11.6% of the serum urate variance. At SLC2A9, the serum urate locus with the largest effect in genome-wide association studies (GWAS), five CpGs are associated with SLC2A9 gene expression. Four CpGs at SLC2A9 have significant causal effects on serum urate levels and/or gout, and two of these partly mediate the effects of urate-associated GWAS variants. In other genes, including SLC7A11 and PHGDH, 17 urate-associated CpGs are associated with conditions defining metabolic syndrome, suggesting that these CpGs may represent a blood DNA methylation signature of cardiometabolic risk factors. This study demonstrates that EWAS can provide new insights into GWAS loci and the correlation of serum urate with other complex traits.
Indexed as
EpigenomeAmino Acid Transport System y+Cohort StudiesCpG IslandsDNA MethylationFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyGlucose Transport Proteins, FacilitativeGoutHumansMaleUric AcidAmino Acid Transport System y+Glucose Transport Proteins, FacilitativeSLC2A9 protein, humanSLC7A11 protein, humanUric Acid
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