Article | Published:

Genome-wide association analyses identify 18 new loci associated with serum urate concentrations

Nature Genetics volume 45, pages 145154 (2013) | Download Citation

Abstract

Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SFMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout.

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Acknowledgements

A detailed list of acknowledgments is provided in the Supplementary Note.

Author information

Author notes

    • Anna Köttgen
    • , Eva Albrecht
    • , Alexander Teumer
    • , Veronique Vitart
    • , Jan Krumsiek
    • , Marina Ciullo
    • , Caroline S Fox
    • , Mark Caulfield
    • , Murielle Bochud
    •  & Christian Gieger

    These authors contributed equally to this work.

    • Marina Ciullo
    • , Caroline S Fox
    • , Mark Caulfield
    • , Murielle Bochud
    •  & Christian Gieger

    These authors jointly directed this work.

Affiliations

  1. Renal Division, Freiburg University Hospital, Freiburg, Germany.

    • Anna Köttgen
    •  & Claudia Hundertmark
  2. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.

    • Anna Köttgen
    • , Adrienne Tin
    • , Josef Coresh
    •  & W H Linda Kao
  3. Institute of Genetic Epidemiology, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany.

    • Eva Albrecht
    • , Konstantin Strauch
    •  & Christian Gieger
  4. Interfaculty Institute for Genetics and Functional Genomics, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany.

    • Alexander Teumer
    • , Claudia Schurmann
    •  & Florian Ernst
  5. Medical Research Council (MRC) Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine (IGMM), University of Edinburgh, Edinburgh, UK.

    • Veronique Vitart
    • , Caroline Hayward
    • , Jennifer Huffman
    • , Albert Tenesa
    • , Susan Campbell
    • , Pau Navarro
    • , Nicholas Hastie
    • , Susan M Farrington
    • , Alan F Wright
    •  & Malcolm G Dunlop
  6. Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany.

    • Jan Krumsiek
    •  & Fabian Theis
  7. Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy.

    • Giorgio Pistis
    • , Cinzia Sala
    •  & Daniela Toniolo
  8. Institute of Genetics and Biophysics A. Buzzati-Traverso, Consiglio Nazionale delle Ricerche (CNR), Naples, Italy.

    • Daniela Ruggiero
    • , Rossella Sorice
    •  & Marina Ciullo
  9. National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA.

    • Conall M O'Seaghdha
    • , Qiong Yang
    • , Andrew D Johnson
    •  & Caroline S Fox
  10. National Heart, Lung, and Blood Institute's Center for Population Studies, Framingham, Massachusetts, USA.

    • Conall M O'Seaghdha
    • , Qiong Yang
    • , Andrew D Johnson
    •  & Caroline S Fox
  11. Renal Division, Massachusetts General Hospital, Boston, Massachusetts, USA.

    • Conall M O'Seaghdha
  12. Estonian Genome Center, University of Tartu, Tartu, Estonia.

    • Toomas Haller
    • , Tõnu Esko
    • , Andres Salumets
    • , Markus Perola
    •  & Andres Metspalu
  13. Department of Biostatistics, Boston University, Boston, Massachusetts, USA.

    • Qiong Yang
    •  & Xuan Liu
  14. Clinical Research Branch, National Institute on Aging, Baltimore, Maryland, USA.

    • Toshiko Tanaka
    • , Jeffrey E Metter
    •  & Luigi Ferrucci
  15. Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland.

    • Zoltán Kutalik
  16. Swiss Institute of Bioinformatics, Lausanne, Switzerland.

    • Zoltán Kutalik
  17. Icelandic Heart Association Research Institute, Kopavogur, Iceland.

    • Albert V Smith
    • , Gauti Kjartan Gislason
    •  & Vilmundur Gudnason
  18. Faculty of Medicine, University of Iceland, Reykjavik, Iceland.

    • Albert V Smith
    •  & Vilmundur Gudnason
  19. University of Maryland School of Medicine, Baltimore, Maryland, USA.

    • Julia Shi
    • , Patrick McArdle
    • , Alan R Shuldiner
    •  & Afshin Parsa
  20. Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.

    • Maksim Struchalin
    • , Abbas Dehghan
    • , Albert Hofman
    • , Fernando Rivadeneira
    • , Andre G Uitterlinden
    •  & Jacqueline C M Witteman
  21. Department of Medicine, Prince Charles Hospital, Chermside, Queensland, Australia.

    • Rita P S Middelberg
  22. Genetic Epidemiology, Queensland Institute of Medical Research, Brisbane, Queensland, Australia.

    • Rita P S Middelberg
    • , Nicholas G Martin
    • , Grant W Montgomery
    •  & John B Whitfield
  23. Clinical Pharmacology Unit, University of Cambridge, Cambridge, UK.

    • Morris J Brown
  24. Division of Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama, USA.

    • Angelo L Gaffo
  25. Birmingham Veterans Affairs Medical Center, University of Alabama at Birmingham, Birmingham, Alabama, USA.

    • Angelo L Gaffo
  26. Institute for Maternal and Child Health, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Burlo Garofolo–Trieste, University of Trieste, Trieste, Italy.

    • Nicola Pirastu
    • , Pio D'Adamo
    •  & Paolo Gasparini
  27. Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, USA.

    • Guo Li
    • , Bruce M Psaty
    •  & David S Siscovick
  28. Faculty of Medicine, University of Split, Split, Croatia.

    • Tatijana Zemunik
    • , Ivana Kolcic
    • , Ozren Polašek
    •  & Igor Rudan
  29. Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR) 8199, Genomics and Molecular Physiology of Metabolic Diseases, Institut Pasteur de Lille, Lille, France.

    • Loic Yengo
    • , Philippe Froguel
    •  & Nabila Bouatia-Naji
  30. CNRS UMR 8524, Laboratory of Mathematics, University Lille 1, Model for Data Analysis and Learning (MODAL) Team, Institut National de Recherche en Informatique et en Automatique (INRIA) Lille Nord–Europe, Lille, France.

    • Loic Yengo
  31. MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.

    • Jing Hua Zhao
    • , Claudia Langenberg
    • , Nicholas J Wareham
    •  & Ruth J F Loos
  32. Subdivision of Genetic Epidemiology, Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.

    • Ayse Demirkan
    • , Aaron Isaacs
    •  & Cornelia M van Duijn
  33. Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, USA.

    • Mary F Feitosa
    • , Aldi Kraja
    • , Qunyuan Zhang
    •  & Ingrid B Borecki
  34. Biology and Genetics Section, Department of Life and Reproduction Sciences, University of Verona, Verona, Italy.

    • Giovanni Malerba
    •  & Elisabetta Trabetti
  35. Department of Psychology, The University of Edinburgh, Edinburgh, UK.

    • Lorna M Lopez
    • , Gail Davies
    • , Alan J Gow
    •  & Ian J Deary
  36. Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK.

    • Lorna M Lopez
    • , Alan J Gow
    •  & Ian J Deary
  37. Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

    • Pim van der Harst
    •  & Hans L Hillege
  38. Institute of Clinical Science, Faculty of Medicine, Imperial College London, London, UK.

    • Xinzhong Li
  39. Ludwigshafen Risk and Cardiovascular Health (LURIC) Study, Freiburg, Germany.

    • Marcus E Kleber
  40. Mannheim Institute of Public Health, Social and Preventive Medicine, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.

    • Marcus E Kleber
    •  & Winfried März
  41. Center for Biomedicine, European Academy Bozen/Bolzano (EURAC), Bolzano, Italy (affiliated institute of the University of Lübeck).

    • Andrew A Hicks
    •  & Peter P Pramstaller
  42. Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

    • Ilja M Nolte
    • , Ronald P Stolk
    •  & Harold Snieder
  43. Uppsala Clinical Research Center, Uppsala University Hospital, Uppsala, Sweden.

    • Asa Johansson
  44. Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.

    • Asa Johansson
    •  & Ulf Gyllensten
  45. Institute of Population Genetics, CNR, Sassari, Italy.

    • Federico Murgia
    • , Laura Frogheri
    • , Laura Portas
    • , Ivana Persico
    • , Mario Pirastu
    •  & Silvia Tore
  46. Centre for Population Health Sciences, The University of Edinburgh Medical School, Edinburgh, UK.

    • Sarah H Wild
    • , Mirna Kirin
    • , James F Wilson
    • , Evropi Theodoratou
    • , Harry Campbell
    •  & Igor Rudan
  47. Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

    • Stephan J L Bakker
  48. Department of Cardiovascular Medicine, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.

    • John F Peden
    • , Anuj Goel
    • , Halit Ongen
    •  & Hugh Watkins
  49. Member of Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands.

    • Abbas Dehghan
    • , Albert Hofman
    • , Fernando Rivadeneira
    • , Andre G Uitterlinden
    •  & Jacqueline C M Witteman
  50. Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Monserrato, Italy.

    • Maristella Steri
    • , Francesco Cucca
    • , Maria Grazia Piras
    •  & Serena Sanna
  51. Roslin Institute, The University of Edinburgh, Edinburgh, UK.

    • Albert Tenesa
  52. Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.

    • Vasiliki Lagou
    •  & Inga Prokopenko
  53. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.

    • Vasiliki Lagou
    •  & Inga Prokopenko
  54. Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.

    • Perttu Salo
    • , Markus Perola
    •  & Veikko Salomaa
  55. King's College London, St Thomas' Hospital Campus, London, UK.

    • Massimo Mangino
    •  & Tim D Spector
  56. Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.

    • Lynda M Rose
    • , Paul M Ridker
    •  & Daniel I Chasman
  57. Fimlab Laboratories, University of Tampere and Tampere University Hospital, Tampere, Finland.

    • Terho Lehtimäki
  58. Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

    • Owen M Woodward
  59. Laboratory for Statistical Analysis, Center for Genomic Medicine, RIKEN, Tokyo, Japan.

    • Yukinori Okada
  60. Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

    • Yukinori Okada
  61. University Heart Center Hamburg, Clinic for General and Interventional Cardiology, Hamburg, Germany.

    • Christian Müller
    •  & Tanja Zeller
  62. School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia.

    • Christopher Oldmeadow
    • , Elizabeth G Holliday
    •  & John Attia
  63. Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.

    • Margus Putku
    • , Tõnu Esko
    • , Elin Org
    • , Maris Laan
    •  & Andres Metspalu
  64. Max Planck Institute of Psychiatry, Munich, Germany.

    • Darina Czamara
    • , Susanne Lucae
    •  & Stefan Kloiber
  65. Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.

    • Peter Kraft
    •  & Poorva Mudgal
  66. Swiss Tropical and Public Health Institute, Basel, Switzerland.

    • Gian Andri Thun
    • , Medea Imboden
    •  & Nicole M Probst-Hensch
  67. University of Basel, Basel, Switzerland.

    • Gian Andri Thun
    • , Medea Imboden
    •  & Nicole M Probst-Hensch
  68. Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany.

    • Anne Grotevendt
    • , Matthias Nauck
    •  & Kathrin Budde
  69. Laboratory of Epidemiology, Demography and Biometry, National Institute on Aging, Bethesda, Maryland, USA.

    • Tamara B Harris
    •  & Lenore J Launer
  70. University of Texas Health Science Center at Houston, Houston, Texas, USA.

    • Eric Boerwinkle
  71. Welch Center for Prevention, Epidemiology and Clinical Research, John Hopkins University, Baltimore, Maryland, USA.

    • Josef Coresh
    •  & W H Linda Kao
  72. Institute of Molecular Biology and Biochemistry, Medical University Graz, Graz, Austria.

    • Helena Schmidt
  73. Department of Neurology, Section of Special Neurology, Medical University Graz, Graz, Austria.

    • Michael Schallert
    •  & Reinhold Schmidt
  74. Laboratory for Genotyping Development, Center for Genomic Medicine, RIKEN, Yokohama, Japan.

    • Michiaki Kubo
  75. Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.

    • Yusuke Nakamura
  76. Laboratory for Cardiovascular Diseases, Center for Genomic Medicine, RIKEN, Yokohama, Japan.

    • Toshihiro Tanaka
  77. William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.

    • Patricia B Munroe
    •  & Mark Caulfield
  78. Leicester National Institute for Health Research (NIHR) Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester, UK.

    • Nilesh J Samani
    •  & Christopher P Nelson
  79. Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.

    • Nilesh J Samani
    •  & Christopher P Nelson
  80. Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, Minnesota, USA.

    • David R Jacobs Jr
  81. Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.

    • Kiang Liu
  82. Intitute for Maternal and Child Health, IRCCS Burlo Garofolo–Trieste, Trieste, Italy.

    • Sheila Ulivi
  83. Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.

    • Jerome I Rotter
  84. Department of Epidemiology, University of Washington, Seattle, Washington, USA.

    • Bruce M Psaty
    •  & David S Siscovick
  85. Department of Medicine, University of Washington, Seattle, Washington, USA.

    • Bruce M Psaty
    •  & David S Siscovick
  86. Group Health Research Institute, Group Health Cooperative, Seattle, Washington, USA.

    • Bruce M Psaty
  87. Department of Health Services, University of Washington, Seattle, Washington, USA.

    • Bruce M Psaty
  88. Department of Medicine, Internal Medicine, Lausanne University Hospital, Lausanne, Switzerland.

    • Peter Vollenweider
    •  & Gerard Waeber
  89. Institute of Physiology, Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland.

    • Olivier Devuyst
  90. Unité Mixte de Recherche en Santé (UMRS) 1018, University Paris Sud 11, Villejuif, France.

    • Beverley Balkau
  91. Department of Genomics of Common Disease, School of Public Health, Imperial College London, Hammersmith Hospital, London, UK.

    • Philippe Froguel
  92. Competence Centre on Reproductive Medicine and Biology, Tartu, Estonia.

    • Andres Salumets
  93. Department of Obstetrics and Gynecology, University of Tartu, Tartu, Estonia.

    • Andres Salumets
  94. Clinical Gerontology Unit, Addenbrooke's Hospital, Cambridge, UK.

    • Kay Tee Khaw
  95. Center for Thrombosis and Hemostasis, University Medical Center Mainz, Johannes Gutenberg University Mainz, Mainz, Germany.

    • Philipp S Wild
  96. Department of Medicine II, University Medical Center Mainz, Johannes Gutenberg University Mainz, Mainz, Germany.

    • Philipp S Wild
  97. School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales, Australia.

    • Rodney J Scott
  98. Chair of Medical Physics, Department of Biomedical Engineering, Tallinn University of Technology, Tallinn, Estonia.

    • Margus Viigimaa
  99. Centre of Cardiology, North Estonia Medical Centre, Tallinn, Estonia.

    • Margus Viigimaa
  100. Geniatric Unit, Azienda Sanitaria Firenze (ASF), Florence, Italy.

    • Stefania Bandinelli
  101. Division of Nephrology, Department of Medicine, University of Verona, Verona, Italy.

    • Antonio Lupo
  102. Institute of Epidemiology II, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany.

    • Angela Döring
  103. Institute of Epidemiology I, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany.

    • Angela Döring
    •  & H-Erich Wichmann
  104. Research Unit of Molecular Epidemiology, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany.

    • Eva Lattka
    • , Melanie Waldenberger
    •  & Norman Klopp
  105. Chair of Genetic Epidemiology, Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-University, Munich, Germany.

    • Konstantin Strauch
  106. Chair of Epidemiology, Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-University, Munich, Germany.

    • H-Erich Wichmann
  107. Klinikum Grosshadern, Munich, Germany.

    • H-Erich Wichmann
  108. University Medical Center Groningen, LifeLines Department, University of Groningen, Groningen, The Netherlands.

    • Marcel Bruinenberg
  109. Faculty of Medicine, National Heart & Lung Institute, Cardiovascular Science, Hammersmith Hospital, Hammersmith Campus, Imperial College London, London, UK.

    • Jaspal S Kooner
  110. Cath Laboratory, Cardiology, Ealing Hospital, Southall, UK.

    • Jaspal S Kooner
    • , Weihua Zhang
    •  & John C Chambers
  111. Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.

    • Weihua Zhang
    •  & John C Chambers
  112. ClinPhenomics Study Center, Frankfurt, Germany.

    • Bernhard R Winkelmann
  113. Division of Endocrinology and Diabetes, Department of Medicine, University Hospital, Ulm, Germany.

    • Bernhard O Boehm
  114. Department of Psychiatry, EMGO Institute for Health and Care Research, VU University Medical Centre, Amsterdam, The Netherlands.

    • Brenda W Penninx
    •  & Johannes H Smit
  115. Department of Psychiatry, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.

    • Brenda W Penninx
  116. Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands.

    • Brenda W Penninx
  117. Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

    • Gary Curhan
    •  & Hyon Choi
  118. Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, Massachusetts, USA.

    • Robert M Plenge
  119. Division of Genetics, Brigham and Women's Hospital, Boston, Massachusetts, USA.

    • Robert M Plenge
  120. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.

    • Robert M Plenge
  121. Division of Experimental Cardiology, Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

    • Irene Mateo Leach
    •  & Wiek H van Gilst
  122. Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.

    • Fernando Rivadeneira
    •  & Andre G Uitterlinden
  123. Institute of Clinical Chemistry, University Hospital of Zurich, Zurich, Switzerland.

    • Arnold von Eckardstein
  124. Laboratory of Genetics, National Institute on Aging, Baltimore, Maryland, USA.

    • Ramaiah Nagaraja
  125. Medical Department, University of Leipzig, Leipzig, Germany.

    • Michael Stumvoll
    •  & Anke Tönjes
  126. Integrated Research and Treatment Center (IFB) Adiposity Diseases, University of Leipzig, Leipzig, Germany.

    • Michael Stumvoll
    •  & Anke Tönjes
  127. Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku, Finland.

    • Antti Jula
    •  & Samuli Ripatti
  128. Institute of Molecular Medicine, University of Helsinki, Helsinki, Finland.

    • Markus Perola
    •  & Samuli Ripatti
  129. Human Genetics, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.

    • So-Youn Shin
    • , Samuli Ripatti
    •  & Nicole Soranzo
  130. Harvard Medical School, Boston, Massachusetts, USA.

    • Paul M Ridker
    •  & Daniel I Chasman
  131. Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland.

    • Mika Kähönen
  132. Department of Medicine, University of Turku and Turku University Hospital, Turku, Finland.

    • Jorma Viikari
  133. Department of Internal Medicine II, University Hospital Regensburg, Regensburg, Germany.

    • Christian Hengstenberg
  134. Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA.

    • James F Meschia
  135. Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, US National Institutes of Health, Bethesda, Maryland, USA.

    • Michael A Nalls
    •  & Andrew B Singleton
  136. Imperial College Cerebrovascular Research Unit, Imperial College London, London, UK.

    • Pankaj Sharma
  137. Laboratory for International Alliance, Center for Genomic Medicine, RIKEN, Yokohama, Japan.

    • Naoyuki Kamatani
  138. Nephrology Division, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland.

    • Michel Burnier
  139. Section of Rheumatology, Boston University School of Medicine, Boston, Massachusetts, USA.

    • Hyon Choi
  140. Clinical Epidemiology Research and Training Unit, Boston University School of Medicine, Boston, Massachusetts, USA.

    • Hyon Choi
  141. Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.

    • Henry Völzke
    •  & Sabine Schipf
  142. University of Texas–Houston Institute of Molecular Medicine, Houston, Texas, USA.

    • Myriam Fornage
  143. University of Texas–Houston School of Public Health, Houston, Texas, USA.

    • Myriam Fornage
  144. Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri, USA.

    • Ingrid B Borecki
  145. Renal Program, Institute of Internal Medicine, Columbus-Gemelli University Hospital, Catholic University, Rome, Italy.

    • Giovanni Gambaro
  146. Department of Endocrinology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

    • Bruce H R Wolffenbuttel
  147. Synlab Centre of Laboratory Diagnostics, Heidelberg, Germany.

    • Winfried März
  148. Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

    • Gerjan Navis
  149. On behalf of PROCARDIS.

    • Hugh Watkins
  150. Institute of Molecular Genetics, CNR, Pavia, Italy.

    • Daniela Toniolo
  151. Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.

    • Olli Raitakari
  152. Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.

    • Olli Raitakari
  153. Division of Endocrinology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.

    • Caroline S Fox
  154. University Institute of Social and Preventive Medicine, Lausanne, Switzerland.

    • Murielle Bochud

Consortia

  1. LifeLines Cohort Study

    A list of contributing members appears in the Supplementary Note.

  2. CARDIoGRAM Consortium

    A list of contributing members appears in the Supplementary Note.

  3. DIAGRAM Consortium

    A list of contributing members appears in the Supplementary Note.

  4. ICBP Consortium

    A list of contributing members appears in the Supplementary Note.

  5. MAGIC Consortium

    A list of contributing members appears in the Supplementary Note.

Authors

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Contributions

Study design: A. Köttgen, C.G., E.A. and M. Caulfield.

Design and/or management of the individual studies: A.A.H., A. Tenesa, A.F.W., A.L., B.M.P., C.G., D.I.C., D.R., E.G.H., E.O., E. Trabetti, G.C., G.P., H. Campbell, H.-E.W., H. Snieder, I.J.D., J.A., J.C., J.F.W., J.V., L.M.R., M. Ciullo, M. Caulfield, M.F., M. Kubo, M.L., M.V., N.H., N.J.S., N. Kamatani, O.M.W., O.P., O.R., P.B.M., P.D., P.G., P.K., P. Mudgal, P.M.R., P.P.P., P.V., R.M.P., R. Sorice, S.H.W., S.M.F., S.U., T.E., T.L., Toshihiro Tanaka, V.S., W.H.L.K., Y.N., Y.O. and Z.K.

Phenotype collection: A.A.H., A.J.G., A.v.E., B.M.P., E.O., G.C., G.G., G.K.G., G.W., H. Snieder, I.J.D., I.K., I. Persico, J.C., J.F.W., J.V., L. Frogheri, M. Ciullo, M. Caulfield, M.G.D., M.G.P., M.J.B., M. Kähönen, M. Kubo, M.L., M. Pirastu, M.V., N.J.S., O.D., O.M.W., O.P., P. Sharma, P.B.M., P.K., P. Mudgal, P.P.P., P.V., S. Schipf, S.H.W., S.M.F., S.T., S.U., T. Zemunik and V.S.

Genotyping: A.A.H., A. Tenesa, A. Teumer, C. Hayward, D.I.C., E.L., F.E., G.C., G.D., G.W.M., I. Persico, J.F.W., M. Ciullo, M. Caulfield, M.E.K., M.G.D., M.G.P., M. Kubo, M.L., M. Putku, M.W., N.J.S., N. Klopp, O.R., P.B.M., P.D., P.M.R., P.P.P., P.v.d.H., R.J.S., S.M.F., T.E., T.L., T. Zeller and T. Zemunik.

Statistical methods and analysis: A. Tenesa, A. Tin, A. Köttgen, A. Teumer, A. Demirkan, C. Hayward, C. Hundertmark, C.G., C. Schurmann, D.C., D.I.C., D.R., E.A., E.G.H., F.M., F.T., G.A.T., G.K.G., G.L., G.M., G.P., I.M.L., I. Prokopenko, J.H., J.K., L.M.L., L.M.R., L.P., M.A.N., M. Steri, M. Bochud, M.E.K., M.F., M. Kähönen, M. Stumvoll, M. Putku, N.P., O.D., P. Mudgal, P.N., P.v.d.H., R.M.P., R.P.S.M., S.C., S.H.W., S. Sanna, T.E., T.H., T.L., V.V., W.H.L.K., X. Li, Y.O. and Z.K.

Interpretation of results: A. Tenesa, A. Tin, A. Köttgen, A.L.G., A. Teumer, B.M.P., C.G., D.R., E.A., G.W.M., H. Campbell, H. Snieder, J.K., M. Ciullo, M.A.N., M. Bochud, M. Caulfield, O.M.W., P.v.d.H., R.M.P., S.H.W., T.H., T.L., Toshihiro Tanaka, V.V., W.H.L.K., Y.O. and Z.K.

Manuscript review: A.A.H., A.B.S., A. Tenesa, A. Dehghan, A.D.J., A. Tin, A. Grotevendt, A. Goel, A.G.U., A.H., A.I., A. Jula, A. Köttgen, A.L., A.L.G., A. Kraja, A.M., A. Döring, A. Tönjes, A.P., A.R.S., A.S., A. Johansson, A. Teumer, A.V.S., B.B., B.H.R.W., B.M.P., B.O.B., B.R.W., B.W.P., C. Hundertmark, C. Hengstenberg, C. Sala, C.L., C.M., C.M.v.D., C.O., C.M.O., C.P.N., C. Schurmann, C.S.F., D.I.C., D.R., D.R.J., D.S.S., D.T., E.B., E.G.H., E. Theodoratou, F.C., F.E., F.R., F.T., G.A.T., G.C., G.G., G.N., G.W.M., H. Campbell, H. Choi, H. Schmidt, H.L.H., H.O., H. Snieder, H.V., H.W., I.B.B., I.K., I.M.L., I.M.N., I. Prokopenko, I.R., J.A., J.B.W., J.C., J.C.C., J.C.M.W., J.E.M., J.F.M., J.F.P., J.F.W., J.H.S., J.H.Z., J.I.R., J.K., J.S., J.S.K., J.V., K.B., K.L., K.S., K.T.K., L.J.L., L. Ferrucci, L.Y., M. Bruinenberg, M.A.N., M. Bochud, M. Caulfield, M. Ciullo, M.F., M.F.F., M.G.D., M.I., M. Burnier, M. Stumvoll, M. Kähönen, M. Kirin, M.M., M.N., M. Perola, M. Struchalin, M. Schallert, M.W., N.B.-N., N.G.M., N.J.W., N. Kamatani, N.M.P.-H., N.S., O.D., O.P., O.R., P. Sharma, P.F., P.K., P. McArdle, P.P.P., P. Salo, P.S.W., P.V., P.v.d.H., Q.Y., Q.Z., R. Schmidt, R.J.F.L., R.J.S., R.N., R.P.S., R. Sorice, S.B., S.H.W., S.J.L.B., S.K., S.L., S.R., S. Sanna, S.-Y.S., T.B.H., T.D.S., T.H., T.L., Toshiko Tanaka, T. Zemunik, U.G., V.G., V.L., V.V., W.H.L.K., W.H.v.G., W.M., W.Z., X. Liu, Y.N., Y.O. and Z.K.

Analysis group: A. Köttgen, A. Teumer, C.G., C. Hundertmark, C.S.F., D.R., E.A., G.P., J.K., Q.Y., T.H., Toshiko Tanaka, V.V. and W.H.L.K.

Writing group: A. Köttgen, A. Teumer, C.G., C.M.O., C.S.F., E.A., J.K., M. Bochud, M. Caulfield, M. Ciullo and V.V.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Anna Köttgen or Veronique Vitart or Murielle Bochud or Christian Gieger.

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Figures 1–9, Supplementary Tables 1–3, 5, 7–9, 11, 14, 16 and 18 and Supplementary Note

Excel files

  1. 1.

    Supplementary Table 4

    All SNPs Associated with Serum Urate at p<5*10-8

  2. 2.

    Supplementary Table 6

    Separate Results from Discovery, Replication and Combined Analyses for SNP-Urate Associations

  3. 3.

    Supplementary Table 10

    All SNPs Associated with Gout at p<1*10-6

  4. 4.

    Supplementary Table 12

    Overall and Sex-Specific Association between SNPs and Fractional Excretion of Uric Acid (FEUA)

  5. 5.

    Supplementary Table 13

    Associations of Urate-Associated SNPs in African Americans and Individuals of Indian and Japanese Ancestry

  6. 6.

    Supplementary Table 15

    Association of Replicated Urate-Associated SNPs with Related Phenotypes

  7. 7.

    Supplementary Table 17

    Functional Network Associations Underlying Supplementary Figure 8 and Supplementary Figure 9

About this article

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DOI

https://doi.org/10.1038/ng.2500