Evidence map›Paper›PMID 31578528›Full record

ArticleNature genetics2019

Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels.

Adrienne Tin, Jonathan Marten, Victoria L Halperin Kuhns, Yong Li, Matthias Wuttke, Holger Kirsten, Karsten B Sieber, Chengxiang Qiu, Mathias Gorski, Zhi Yu and 218 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 247 papers, 13 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
247citing papers in PubMed, 13 pooled it
33.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

247 citing papers in PubMed, 13 syntheses or guidelines pooled it, 418 citations in OpenAlex.

  1. Pooled it
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  13. Pooled it
  14. Trial
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  17. Review
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187 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

228 authors at 20 institutions in 20 countries.

Adrienne Tin *Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. atin1@jhu.edu.ORCID http://orcid.org/0000-0002-4207-5866
Jonathan Marten *Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0001-6916-2014
Victoria L Halperin Kuhns *Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, USA.
Yong Li *Institute of Genetic Epidemiology, Department of Biometry, Epidemiology and Medical Bioinformatics, Faculty of Medicine and Medical Center-University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0000-0003-2651-8791
Matthias Wuttke *Institute of Genetic Epidemiology, Department of Biometry, Epidemiology and Medical Bioinformatics, Faculty of Medicine and Medical Center-University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0000-0003-3420-5082
Holger Kirsten *Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.ORCID http://orcid.org/0000-0002-3126-7950
Karsten B SieberTarget Sciences-Genetics, GlaxoSmithKline, Collegeville, PA, USA.
Chengxiang QiuDepartment of Medicine and Genetics, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-6346-8669
Mathias GorskiDepartment of Nephrology, University Hospital Regensburg, Regensburg, Germany.
Zhi YuDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Ayush GiriDivision of Quantitative Sciences, Department of Obstetrics & Gynecology, Vanderbilt Genetics Institute, Vanderbilt Epidemiology Center, Institute for Medicine and Public Health, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID http://orcid.org/0000-0002-7786-4670
Gardar SveinbjornssondeCODE Genetics, Amgen Inc., Reykjavik, Iceland.
Man LiDepartment of Medicine, Division of Nephrology and Hypertension, University of Utah, Salt Lake City, UT, USA.ORCID http://orcid.org/0000-0002-3839-0281
Audrey Y ChuGenetics, Merck & Co., Inc, Kenilworth, NJ, USA.
Anselm HoppmannInstitute of Genetic Epidemiology, Department of Biometry, Epidemiology and Medical Bioinformatics, Faculty of Medicine and Medical Center-University of Freiburg, Freiburg, Germany.
Luke J O'ConnorEpidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.ORCID http://orcid.org/0000-0003-2730-9668
Bram PrinsStrangeways Research Laboratory, University of Cambridge, Cambridge, UK.
Teresa NutileInstitute of Genetics and Biophysics Adriano Buzzati-Traverso-CNR, Naples, Italy.
Damia NoceEurac Research, Institute for Biomedicine, Bolzano, Italy.
Masato AkiyamaLaboratory for Statistical Analysis, RIKEN Centre for Integrative Medical Sciences, Yokohama (Kanagawa), Japan.
Massimiliano CoccaInstitute for Maternal and Child Health-IRCCS Burlo Garofolo, Trieste, Italy.
Sahar GhasemiInstitute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
Peter J van der MostDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.ORCID http://orcid.org/0000-0001-8450-3518
Katrin HornInstitute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.ORCID http://orcid.org/0000-0002-5307-6936
Yizhe XuDepartment of Medicine, Division of Nephrology and Hypertension, University of Utah, Salt Lake City, UT, USA.
Christian FuchsbergerEurac Research, Institute for Biomedicine, Bolzano, Italy.
Sanaz SedaghatDepartment of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Saima AfaqDepartment of Epidemiology and Biostatistics, Faculty of Medicine, School of Public Health, Imperial College London, London, UK.
Najaf AminDepartment of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Johan ÄrnlövDepartment of Neurobiology, Care Sciences and Society, Division of Family Medicine and Primary Care, Karolinska Institutet, Stockholm, Sweden.
Stephan J L BakkerDepartment of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Nisha BansalDivision of Nephrology, University of Washington, Seattle, WA, USA.
Daniela BaptistaCardiology, Geneva University Hospitals, Geneva, Switzerland.
Sven BergmannDepartment of Computational Biology, University of Lausanne, Lausanne, Switzerland.ORCID http://orcid.org/0000-0002-6785-9034
Mary L BiggsCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
Ginevra BiinoInstitute of Molecular Genetics, National Research Council of Italy, Pavia, Italy.ORCID http://orcid.org/0000-0002-9936-946X
Eric BoerwinkleHuman Genetics Centre, University of Texas Health Science Centre, Houston, TX, USA.
Erwin P BottingerHasso Plattner Institute for Digital Health at Mount Sinai, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Thibaud S BoutinMedical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Marco BrumatUniversity of Trieste, Department of Medicine, Surgery and Health Sciences, Trieste, Italy.ORCID http://orcid.org/0000-0003-3268-039X
Ralph BurkhardtLIFE Research Centre for Civilization Diseases, University of Leipzig, Leipzig, Germany.
Eric CampanaUniversity of Trieste, Department of Medicine, Surgery and Health Sciences, Trieste, Italy.
Archie CampbellCentre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0003-0198-5078
Harry CampbellCentre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
Robert J CarrollDepartment of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA.
Eulalia CatamoInstitute for Maternal and Child Health-IRCCS Burlo Garofolo, Trieste, Italy.
John C ChambersDepartment of Epidemiology and Biostatistics, Faculty of Medicine, School of Public Health, Imperial College London, London, UK.
Marina CiulloInstitute of Genetics and Biophysics Adriano Buzzati-Traverso-CNR, Naples, Italy.
Maria Pina ConcasInstitute for Maternal and Child Health-IRCCS Burlo Garofolo, Trieste, Italy.ORCID http://orcid.org/0000-0003-3598-2537
Josef CoreshDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-4598-0669
Tanguy CorreDepartment of Computational Biology, University of Lausanne, Lausanne, Switzerland.
Daniele CusiInstitute of Biomedical Technologies, Italy National Research Council, Milano, Italy.
Sala Cinzia FelicitaSan Raffaele Research Institute, Milano, Italy.ORCID http://orcid.org/0000-0003-2514-2075
Martin H de BorstDepartment of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.ORCID http://orcid.org/0000-0002-4127-8733
Alessandro De GrandiEurac Research, Institute for Biomedicine, Bolzano, Italy.
Renée de MutsertDepartment of Clinical Epidemiology, Leiden University Medical Centre, Leiden, the Netherlands.
Aiko P J de VriesSection of Nephrology, Department of Internal Medicine, Leiden University Medical Centre, Leiden, the Netherlands.
Graciela DelgadoFifth Department of Medicine (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Ayşe DemirkanDepartment of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Olivier DevuystInstitute of Physiology, University of Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0003-3744-4767
Katalin DittrichDepartment of Women and Child Health, Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany.
Kai-Uwe EckardtDepartment of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Georg EhretCardiology, Geneva University Hospitals, Geneva, Switzerland.ORCID http://orcid.org/0000-0002-5730-0675
Karlhans EndlichDZHK (German Center for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany.ORCID http://orcid.org/0000-0001-6052-6061
Michele K EvansLaboratory of Epidemiology and Population Sciences, National Institute on Aging, Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.
Ron T GansevoortDepartment of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Paolo GaspariniInstitute for Maternal and Child Health-IRCCS Burlo Garofolo, Trieste, Italy.
Vilmantas GiedraitisDepartment of Public Health and Caring Sciences, Molecular Geriatrics, Uppsala University, Uppsala, Sweden.ORCID http://orcid.org/0000-0003-3423-2021
Christian GiegerResearch Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Centre for Environmental Health, Neuherberg, Germany.
Giorgia GirottoInstitute for Maternal and Child Health-IRCCS Burlo Garofolo, Trieste, Italy.ORCID http://orcid.org/0000-0003-4507-6589
Martin GögeleEurac Research, Institute for Biomedicine, Bolzano, Italy.
Scott D GordonQIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.ORCID http://orcid.org/0000-0001-7623-328X
Daniel F GudbjartssondeCODE Genetics, Amgen Inc., Reykjavik, Iceland.ORCID http://orcid.org/0000-0002-5222-9857
Vilmundur GudnasonIcelandic Heart Association, Kópavogur, Iceland.ORCID http://orcid.org/0000-0001-5696-0084
German Chronic Kidney Disease Study
Toomas HallerEstonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
Pavel HametMontreal University Hospital Research Centre, Centre Hospitalier de lUniversité de Montréal, Montreal, Quebec, Canada.
Tamara B HarrisLaboratory of Epidemiology and Population Sciences, National Institute on Aging, Intramural Research Program, National Institutes of Health, Bethesda, MD, USA.
Caroline HaywardMedical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0002-9405-9550
Andrew A HicksEurac Research, Institute for Biomedicine, Bolzano, Italy.ORCID http://orcid.org/0000-0001-6320-0411
Edith HoferClinical Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Graz, Austria.
Hilma HolmdeCODE Genetics, Amgen Inc., Reykjavik, Iceland.
Wei HuangDepartment of Genetics, Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Centre, Shanghai, China.
Nina Hutri-KähönenDepartment of Clinical Chemistry, Fimlab Laboratories, and Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Shih-Jen HwangNational Heart, Lung, and Blood Institute Framingham Heart Study, Framingham, MA, USA.
M Arfan IkramDepartment of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.ORCID http://orcid.org/0000-0003-0372-8585
Raychel M LewisDepartment of Physiology, University of Maryland School of Medicine, Baltimore, MD, USA.
Erik IngelssonDepartment of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-2256-6972
Johanna JakobsdottirIcelandic Heart Association, Kópavogur, Iceland.
Ingileif JonsdottirdeCODE Genetics, Amgen Inc., Reykjavik, Iceland.ORCID http://orcid.org/0000-0001-8339-150X
Helgi JonssonLandspitalinn University Hospital, Reykjavík, Iceland.
Peter K JoshiCentre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0002-6361-5059
Navya Shilpa JosyulaGeisinger Research, Biomedical and Translational Informatics Institute, Rockville, MD, USA.ORCID http://orcid.org/0000-0003-2782-8812
Bettina JungDepartment of Nephrology, University Hospital Regensburg, Regensburg, Germany.
Mika KähönenDepartment of Clinical Physiology, Tampere University Hospital, and Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Yoichiro KamataniLaboratory for Statistical Analysis, RIKEN Centre for Integrative Medical Sciences, Yokohama (Kanagawa), Japan.ORCID http://orcid.org/0000-0001-8748-5597
Masahiro KanaiLaboratory for Statistical Analysis, RIKEN Centre for Integrative Medical Sciences, Yokohama (Kanagawa), Japan.ORCID http://orcid.org/0000-0001-5165-4408
Shona M KerrMedical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Wieland KiessLIFE Research Centre for Civilization Diseases, University of Leipzig, Leipzig, Germany.
Marcus E KleberFifth Department of Medicine (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Medical Faculty Mannheim, University of Heidelberg, 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 KoonerDepartment of Cardiology, Ealing Hospital, London, UK.
Antje KörnerLIFE Research Centre for Civilization Diseases, University of Leipzig, Leipzig, Germany.
Peter KovacsIntegrated Research and Treatment Centre Adiposity Diseases, University of Leipzig, Leipzig, Germany.ORCID http://orcid.org/0000-0002-0290-5423
Bernhard K KrämerFifth Department of Medicine (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Florian KronenbergDivision of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.ORCID http://orcid.org/0000-0003-2229-1120
Michiaki KuboRIKEN Centre for Integrative Medical Sciences, Yokohama (Kanagawa), Japan.
Brigitte KühnelResearch Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Centre for Environmental Health, Neuherberg, Germany.
Martina La BiancaInstitute for Maternal and Child Health-IRCCS Burlo Garofolo, Trieste, Italy.
Leslie A LangeDivision of Biomedical Informatics and Personalized Medicine, School of Medicine, University of Colorado Denver-Anschutz Medical Campus, Aurora, CO, USA.
Benjamin LehneDepartment of Epidemiology and Biostatistics, Faculty of Medicine, School of Public Health, Imperial College London, London, UK.
Terho LehtimäkiDepartment of Clinical Chemistry, Fimlab Laboratories, and Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Lifelines Cohort Study
Jun LiuDepartment of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.ORCID http://orcid.org/0000-0001-5288-3042
Markus LoefflerInstitute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
Ruth J F LoosThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0002-8532-5087
Leo-Pekka LyytikäinenDepartment of Clinical Chemistry, Fimlab Laboratories, and Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.ORCID http://orcid.org/0000-0002-7200-5455
Reedik MagiEstonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
Anubha MahajanWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0001-5585-3420
Nicholas G MartinQIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.ORCID http://orcid.org/0000-0003-4069-8020
Winfried MärzFifth Department of Medicine (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Deborah MascalzoniEurac Research, Institute for Biomedicine, Bolzano, Italy.
Koichi MatsudaLaboratory of Clinical Genome Sequencing, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.
Christa MeisingerIndependent Research Group Clinical Epidemiology, Helmholtz Zentrum München, German Research Centre for Environmental Health, Neuherberg, Germany.
Thomas MeitingerGerman Centre for Cardiovascular Research, Partner Site Munich Heart Alliance, Munich, Germany.
Andres MetspaluEstonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.ORCID http://orcid.org/0000-0002-3718-796X
Yuri MilaneschiDepartment of Psychiatry, Amsterdam Neuroscience and Amsterdam Public Health Research Institute, Amsterdam University Medical Centers, Amsterdam, the Netherlands.
V. A. Million Veteran Program
Christopher J O'DonnellVA Boston Healthcare System, Boston, MA, USA.
Otis D WilsonVanderbilt University Medical Centre, Division of Nephrology & Hypertension, Nashville, TN, USA.
J Michael GazianoDepartment of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Pashupati P MishraDepartment of Clinical Chemistry, Fimlab Laboratories, and Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Karen L MohlkeDepartment of Genetics, University of North Carolina, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0001-6721-153X
Nina MononenDepartment of Clinical Chemistry, Fimlab Laboratories, and Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Grant W MontgomeryUniversity of Queensland, St Lucia, Queensland, Australia.ORCID http://orcid.org/0000-0002-4140-8139
Dennis O Mook-KanamoriDepartment of Clinical Epidemiology, Leiden University Medical Centre, Leiden, the Netherlands.
Martina Müller-NurasyidGerman Centre for Cardiovascular Research, Partner Site Munich Heart Alliance, Munich, Germany.ORCID http://orcid.org/0000-0003-3793-5910
Girish N NadkarniThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Mike A NallsLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Matthias NauckDZHK (German Center for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany.
Kjell NikusDepartment of Cardiology, Heart Center, Tampere University Hospital, Tampere, Finland.
Boting NingDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Ilja M NolteDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.ORCID http://orcid.org/0000-0001-5047-4077
Raymond NoordamSection of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Centre, Leiden, the Netherlands.
Jeffrey R O'ConnellUniversity of Maryland School of Medicine, Baltimore, MD, USA.
Isleifur OlafssonDepartment of Clinical Biochemistry, Landspitali University Hospital, Reykjavik, Iceland.
Sandosh PadmanabhanInstitute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
Brenda W J H PenninxDepartment of Psychiatry, Amsterdam Neuroscience and Amsterdam Public Health Research Institute, Amsterdam University Medical Centers, Amsterdam, the Netherlands.
Thomas PerlsDepartment of Medicine, Geriatrics Section, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA.
Annette PetersInstitute of Epidemiology, Helmholtz Zentrum München-German Research Centre for Environmental Health, Neuherberg, Germany.
Mario PirastuInstitute of Genetic and Biomedical Research, National Research Council of Italy, UOS of Sassari, Sassari, Italy.
Nicola PirastuCentre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0002-5363-3886
Giorgio PistisDepartment of Psychiatry, University Hospital of Lausanne, Lausanne, Switzerland.
Ozren PolasekFaculty of Medicine, University of Split, Split, Croatia.
Belen PonteNephrology Service, Department of Specialties in Internal Medicine, University Hospitals of Geneva, Geneva, Switzerland.
David J PorteousCentre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Tanja PoulainLIFE Research Centre for Civilization Diseases, University of Leipzig, Leipzig, Germany.
Michael H PreussThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0001-5266-8465
Ton J RabelinkSection of Nephrology, Department of Internal Medicine, Leiden University Medical Centre, Leiden, the Netherlands.
Laura M RaffieldDepartment of Genetics, University of North Carolina, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0002-7892-193X
Olli T RaitakariDepartment of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
Rainer RettigInstitute of Physiology, University Medicine Greifswald, Karlsburg, Germany.
Myriam RheinbergerDepartment of Nephrology, University Hospital Regensburg, Regensburg, Germany.
Kenneth M RiceDepartment of Biostatistics, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-3071-7278
Federica RizziDepartment of Health Sciences, University of Milan, Milano, Italy.ORCID http://orcid.org/0000-0002-4606-6553
Antonietta RobinoInstitute for Maternal and Child Health-IRCCS Burlo Garofolo, Trieste, Italy.
Igor RudanCentre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0001-6993-6884
Alena KrajcoviechovaCenter for Cardiovascular Prevention, First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic.
Renata CifkovaCenter for Cardiovascular Prevention, First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic.
Rico RueediDepartment of Computational Biology, University of Lausanne, Lausanne, Switzerland.
Daniela RuggieroInstitute of Genetics and Biophysics Adriano Buzzati-Traverso-CNR, Naples, Italy.
Kathleen A RyanDivision of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, MD, USA.
Yasaman SabaMolecular Biology and Biochemistry, Gottfried Schatz Research Centre for Cell Signaling, Metabolism and Aging, Medical University of Graz, Graz, Austria.
Erika SalviDepartment of Health Sciences, University of Milan, Milano, Italy.
Helena SchmidtInstitute of Molecular Biology and Biochemistry, Centre for Molecular Medicine, Medical University of Graz, Graz, Austria.
Reinhold SchmidtClinical Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Graz, Austria.
Christian M ShafferDepartment of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA.
Albert V SmithFaculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland.ORCID http://orcid.org/0000-0003-1942-5845
Blair H SmithDivision of Population Health and Genomics, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.
Cassandra N SpracklenDepartment of Genetics, University of North Carolina, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0003-3590-7182
Konstantin StrauchInstitute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Centre for Environmental Health, Neuherberg, Germany.
Michael StumvollDivision of Endocrinology, Nephrology and Rheumatology, University of Leipzig, Leipzig, Germany.
Patrick SulemdeCODE Genetics, Amgen Inc., Reykjavik, Iceland.ORCID http://orcid.org/0000-0001-7123-6123
Salman M TajuddinLaboratory of Epidemiology and Population Sciences, National Institute on Aging, Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-7919-8528
Andrej TerenLIFE Research Centre for Civilization Diseases, University of Leipzig, Leipzig, Germany.
Joachim ThieryLIFE Research Centre for Civilization Diseases, University of Leipzig, Leipzig, 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
Unnur ThorsteinsdottirdeCODE Genetics, Amgen Inc., Reykjavik, Iceland.
Daniela TonioloSan Raffaele Research Institute, Milano, Italy.
Anke TönjesDepartment of Endocrinology and Nephrology, University of Leipzig, Leipzig, Germany.
Johanne TremblayMontreal University Hospital Research Centre, Centre Hospitalier de lUniversité de Montréal, Montreal, Quebec, Canada.
André G UitterlindenDepartment of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.ORCID http://orcid.org/0000-0002-7276-3387
Simona VaccargiuInstitute of Genetic and Biomedical Research, National Research Council of Italy, UOS of Sassari, Sassari, Italy.
Pim van der HarstDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.ORCID http://orcid.org/0000-0002-2713-686X
Cornelia M van DuijnDepartment of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Niek VerweijDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.ORCID http://orcid.org/0000-0002-4303-7685
Uwe VölkerDZHK (German Center for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany.ORCID http://orcid.org/0000-0002-5689-3448
Peter VollenweiderInternal Medicine, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland.
Gerard WaeberInternal Medicine, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland.
Melanie WaldenbergerResearch Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Centre for Environmental Health, Neuherberg, Germany.
John B WhitfieldQIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.ORCID http://orcid.org/0000-0002-1103-0876
Sarah H WildCentre for Population Health Sciences, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0001-7824-2569
James F WilsonMedical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0001-5751-9178
Qiong YangDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA.ORCID http://orcid.org/0000-0002-3658-1375
Weihua ZhangDepartment of Epidemiology and Biostatistics, Faculty of Medicine, School of Public Health, Imperial College London, London, UK.
Alan B ZondermanLaboratory of Epidemiology and Population Sciences, National Institute on Aging, Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.
Murielle BochudCenter for Primary Care and Public Health (Unisanté), University of Lausanne, Lausanne, Switzerland.
James G WilsonDepartment of Physiology and Biophysics, University of Mississippi Medical Centre, Jackson, MS, USA.
Sarah A PendergrassGeisinger Research, Biomedical and Translational Informatics Institute, Danville, PA, USA.
Kevin HoKidney Health Research Institute, Geisinger, Danville, PA, USA.
Afshin ParsaDivision of Kidney, Urologic and Hematologic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Peter P PramstallerEurac Research, Institute for Biomedicine, Bolzano, Italy.
Bruce M PsatyCardiovascular Health Research Unit, Department of Medicine, Department of Epidemiology, Department of Health Service, University of Washington, Seattle, WA, USA.
Carsten A BögerDepartment of Nephrology, University Hospital Regensburg, Regensburg, Germany.
Harold SniederDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.ORCID http://orcid.org/0000-0003-1949-2298
Adam S ButterworthDepartment of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Yukinori OkadaLaboratory for Statistical Analysis, RIKEN Centre for Integrative Medical Sciences, Osaka, Japan.ORCID http://orcid.org/0000-0002-0311-8472
Todd L EdwardsDivision of Epidemiology, Department of Medicine, Vanderbilt Genetics Institute, Vanderbilt University Medical Centre, Nashville, TN, USA.ORCID http://orcid.org/0000-0003-4318-6119
Kari StefanssondeCODE Genetics, Amgen Inc., Reykjavik, Iceland.ORCID http://orcid.org/0000-0003-1676-864X
Katalin SusztakDepartment of Medicine and Genetics, University of Pennsylvania, Philadelphia, PA, USA.
Markus ScholzInstitute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.ORCID http://orcid.org/0000-0002-4059-1779
Iris M HeidDepartment of Genetic Epidemiology, University of Regensburg, Regensburg, Germany.
Adriana M HungVanderbilt University Medical Centre, Division of Nephrology & Hypertension, Nashville, TN, USA.ORCID http://orcid.org/0000-0002-3203-1608
Alexander TeumerInstitute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
Cristian PattaroEurac Research, Institute for Biomedicine, Bolzano, Italy.
Owen M WoodwardDepartment of Physiology, University of Maryland School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0001-9514-2180
Veronique VitartMedical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0002-4991-3797
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
Eurac Research · ITUniversity Medical Center Groningen · NLdeCODE Genetics (Iceland) · ISUniversity of Maryland, Baltimore · USLeiden University · NLNational Institutes of Health · USJohns Hopkins University · USTampere University · FIBoston University · USErasmus MC · NLIRCCS Materno Infantile Burlo Garofolo · ITUniversity of North Carolina at Chapel Hill · USUniversity of Trieste · ITHeidelberg University · DEHelmholtz Zentrum München · DEQIMR Berghofer Medical Research Institute · AUSIB Swiss Institute of Bioinformatics · CHUniversity Hospital Regensburg · DEUniversity of Freiburg · DEUniversity of Iceland · IS

Funding

Stanford Islet Research CoreP30DK116074 · NIDDK · STANFORD UNIVERSITY · PI Seung K Kim · 2017 to 2026
$19.5M
Training Program in Bioinformatics and Integrative GenomicsT32HG002295 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Peter J Park · 2001 to 2026
$15.8M
Research BaseP30DK090868 · NIDDK · UNIVERSITY OF MARYLAND BALTIMORE · PI SELIGER, STEPHEN L. · 2010 to 2019
$11.1M
Building Interdisciplinary Research Careers in Women's HealthK12HD043483 · NICHD · VANDERBILT UNIVERSITY MEDICAL CENTER · PI HARTMANN, KATHERINE E, MAJOR, AMY S · 2002 to 2023
$10.3M
CHARGE Consortium: Omics Discovery for CVD and Aging PhenotypesR01HL105756 · NHLBI · UNIVERSITY OF WASHINGTON · PI Bruce M Psaty, NICHOLAS L SMITH · 2011 to 2026
$9.5M
Rare variants and NHLBI traits in deeply phenotyped cohortsR01HL120393 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M, RICE, KENNETH M. · 2014 to 2016
$8.9M
CHS research resources for the cardiovascular health of older adultsU01HL130114 · NHLBI · UNIVERSITY OF WASHINGTON · PI BURKE, GREGORY L, KRONMAL, RICHARD A · 2016 to 2019
$6.6M
Rare variants and NHLBI traits in deeply phenotyped cohortsU01HL120393 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M, RICE, KENNETH M. · 2017 to 2018
$5.6M
The Genetic Epidemiology of Heart, Lung, and Blood TraitsTraining Grant (GenHLB)T32HL129982 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Christy Leigh Avery, KAREN L. MOHLKE · 2016 to 2026
$3.8M
Identifying Novel Biological Pathways for Gout using DNA Methylation and GeneticsR01AR073178 · NIAMS · UNIVERSITY OF MISSISSIPPI MED CTR · PI TIN, ADRIENNE · 2018 to 2023
$2.5M
Molecular Mechanisms of Uric Acid HomeostasisR01DK114091 · NIDDK · UNIVERSITY OF MARYLAND BALTIMORE · PI WOODWARD, OWEN M · 2017 to 2020
$1.4M
British Heart Foundation RG/13/13/30194British Heart Foundation RG/18/13/33946Medical Research Council MC_PC_17228Medical Research Council MC_QA137853NHGRI NIH HHS T32 HG002295NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL120393NHLBI NIH HHS T32 HL129982NHLBI NIH HHS U01 HL120393NHLBI NIH HHS U01 HL130114NIAMS NIH HHS R01 AR073178NICHD NIH HHS K12 HD043483NIDDK NIH HHS P30 DK116074NIDDK NIH HHS R01 DK114091Wellcome Trust 212945/Z/18/Z
6 · The paper itself

Abstract

Elevated serum urate levels cause gout and correlate with cardiometabolic diseases via poorly understood mechanisms. We performed a trans-ancestry genome-wide association study of serum urate in 457,690 individuals, identifying 183 loci (147 previously unknown) that improve the prediction of gout in an independent cohort of 334,880 individuals. Serum urate showed significant genetic correlations with many cardiometabolic traits, with genetic causality analyses supporting a substantial role for pleiotropy. Enrichment analysis, fine-mapping of urate-associated loci and colocalization with gene expression in 47 tissues implicated the kidney and liver as the main target organs and prioritized potentially causal genes and variants, including the transcriptional master regulators in the liver and kidney, HNF1A and HNF4A. Experimental validation showed that HNF4A transactivated the promoter of ABCG2, encoding a major urate transporter, in kidney cells, and that HNF4A p.Thr139Ile is a functional variant. Transcriptional coregulation within and across organs may be a general mechanism underlying the observed pleiotropy between urate and cardiometabolic traits.

Indexed as

Genetic MarkersPolymorphism, Single NucleotideSignal TransductionATP Binding Cassette Transporter, Subfamily G, Member 2Cardiovascular DiseasesCohort StudiesGenetic LociGenetic Predisposition to DiseaseGenome-Wide Association StudyGoutHepatocyte Nuclear Factor 1-alphaHepatocyte Nuclear Factor 4HumansKidneyLiverMetabolic DiseasesABCG2 protein, humanATP Binding Cassette Transporter, Subfamily G, Member 2Genetic MarkersHepatocyte Nuclear Factor 1-alphaHepatocyte Nuclear Factor 4HNF1A protein, humanHNF4A protein, humanNeoplasm ProteinsUric Acid

Identifiers

PMID31578528
PMCPMC6858555
OpenAlexW2977833465

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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.