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

1. So, A. & Thorens, B. Uric acid transport and disease. J. Clin. Invest. 120, 1791–1799 (2010).

   Article  CAS  Google Scholar 

2. Zhu, Y., Pandya, B.J. & Choi, H.K. Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007–2008. Arthritis Rheum. 63, 3136–3141 (2011).

   Article  Google Scholar 

3. Arromdee, E., Michet, C.J., Crowson, C.S., O′Fallon, W.M. & Gabriel, S.E. Epidemiology of gout: is the incidence rising? J. Rheumatol. 29, 2403–2406 (2002).

   PubMed  Google Scholar 

4. Wallace, K.L., Riedel, A.A., Joseph-Ridge, N. & Wortmann, R. Increasing prevalence of gout and hyperuricemia over 10 years among older adults in a managed care population. J. Rheumatol. 31, 1582–1587 (2004).

   PubMed  Google Scholar 

5. Yoo, H.G. et al. Prevalence of insulin resistance and metabolic syndrome in patients with gouty arthritis. Rheumatol. Int. 31, 485–491 (2011).

   Article  CAS  Google Scholar 

6. Singh, J.A. Quality of life and quality of care for patients with gout. Curr. Rheumatol. Rep. 11, 154–160 (2009).

   Article  Google Scholar 

7. Becker, M.A. et al. Quality of life and disability in patients with treatment-failure gout. J. Rheumatol. 36, 1041–1048 (2009).

   Article  Google Scholar 

8. Brook, R.A. et al. The economic burden of gout on an employed population. Curr. Med. Res. Opin. 22, 1381–1389 (2006).

   Article  Google Scholar 

9. Hediger, M.A., Johnson, R.J., Miyazaki, H. & Endou, H. Molecular physiology of urate transport. Physiology (Bethesda) 20, 125–133 (2005).

   CAS  Google Scholar 

10. Whitfield, J.B. & Martin, N.G. Inheritance and alcohol as factors influencing plasma uric acid levels. Acta Genet. Med. Gemellol. (Roma) 32, 117–126 (1983).

    Article  CAS  Google Scholar 

11. Yang, Q. et al. Genome-wide search for genes affecting serum uric acid levels: the Framingham Heart Study. Metabolism 54, 1435–1441 (2005).

    Article  CAS  Google Scholar 

12. Nath, S.D. et al. Genome scan for determinants of serum uric acid variability. J. Am. Soc. Nephrol. 18, 3156–3163 (2007).

    Article  CAS  Google Scholar 

13. Li, S. et al. The GLUT9 gene is associated with serum uric acid levels in Sardinia and Chianti cohorts. PLoS Genet. 3, e194 (2007).

    Article  Google Scholar 

14. Doring, A. et al. SLC2A9 influences uric acid concentrations with pronounced sex-specific effects. Nat. Genet. 40, 430–436 (2008).

    Article  Google Scholar 

15. Vitart, V. et al. SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout. Nat. Genet. 40, 437–442 (2008).

    Article  CAS  Google Scholar 

16. Dehghan, A. et al. Association of three genetic loci with uric acid concentration and risk of gout: a genome-wide association study. Lancet 372, 1953–1961 (2008).

    Article  CAS  Google Scholar 

17. Kolz, M. et al. Meta-analysis of 28,141 individuals identifies common variants within five new loci that influence uric acid concentrations. PLoS Genet. 5, e1000504 (2009).

    Article  Google Scholar 

18. Yang, Q. et al. Multiple genetic loci influence serum urate levels and their relationship with gout and cardiovascular disease risk factors. Circ. Cardiovasc. Genet. 3, 523–530 (2010).

    Article  CAS  Google Scholar 

19. Woodward, O.M. et al. Identification of a urate transporter, ABCG2, with a common functional polymorphism causing gout. Proc. Natl. Acad. Sci. USA 106, 10338–10342 (2009).

    Article  CAS  Google Scholar 

20. Visscher, P.M., Brown, M.A., McCarthy, M.I. & Yang, J. Five years of GWAS discovery. Am. J. Hum. Genet. 90, 7–24 (2012).

    Article  CAS  Google Scholar 

21. Hindorff, L.A. et al. Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc. Natl. Acad. Sci. USA 106, 9362–9367 (2009).

    Article  CAS  Google Scholar 

22. Suhre, K. et al. Human metabolic individuality in biomedical and pharmaceutical research. Nature 477, 54–60 (2011).

    Article  CAS  Google Scholar 

23. Sato, M. et al. Renal secretion of uric acid by organic anion transporter 2 (OAT2/SLC22A7) in human. Biol. Pharm. Bull. 33, 498–503 (2010).

    Article  CAS  Google Scholar 

24. Wallace, S.L. et al. Preliminary criteria for the classification of the acute arthritis of primary gout. Arthritis Rheum. 20, 895–900 (1977).

    Article  CAS  Google Scholar 

25. Choi, H.K., Atkinson, K., Karlson, E.W., Willett, W. & Curhan, G. Purine-rich foods, dairy and protein intake, and the risk of gout in men. N. Engl. J. Med. 350, 1093–1103 (2004).

    Article  CAS  Google Scholar 

26. Ehret, G.B. et al. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature 478, 103–109 (2011).

    Article  CAS  Google Scholar 

27. Raychaudhuri, S. et al. Identifying relationships among genomic disease regions: predicting genes at pathogenic SNP associations and rare deletions. PLoS Genet. 5, e1000534 (2009).

    Article  Google Scholar 

28. Ishizuka, T. et al. The human phosphoribosylpyrophosphate synthetase–associated protein 39 gene (PRPSAP1) is located in the chromosome region 17q24-q25. Genomics 33, 332–334 (1996).

    Article  CAS  Google Scholar 

29. Luo, Z., Saha, A.K., Xiang, X. & Ruderman, N.B. AMPK, the metabolic syndrome and cancer. Trends Pharmacol. Sci. 26, 69–76 (2005).

    Article  CAS  Google Scholar 

30. Tong, X., Zhao, F., Mancuso, A., Gruber, J.J. & Thompson, C.B. The glucose-responsive transcription factor ChREBP contributes to glucose-dependent anabolic synthesis and cell proliferation. Proc. Natl. Acad. Sci. USA 106, 21660–21665 (2009).

    Article  CAS  Google Scholar 

31. Levine, A.J. & Puzio-Kuter, A.M. The control of the metabolic switch in cancers by oncogenes and tumor suppressor genes. Science 330, 1340–1344 (2010).

    Article  CAS  Google Scholar 

32. Iynedjian, P.B. Molecular physiology of mammalian glucokinase. Cell. Mol. Life Sci. 66, 27–42 (2009).

    Article  CAS  Google Scholar 

33. Quinones Galvan, A. et al. Effect of insulin on uric acid excretion in humans. Am. J. Physiol. 268, E1–E5 (1995).

    CAS  PubMed  Google Scholar 

34. Ter Maaten, J.C. et al. Renal handling of urate and sodium during acute physiological hyperinsulinaemia in healthy subjects. Clin. Sci. (Lond.) 92, 51–58 (1997).

    Article  CAS  Google Scholar 

35. Becker, M.A. et al. Febuxostat compared with allopurinol in patients with hyperuricemia and gout. N. Engl. J. Med. 353, 2450–2461 (2005).

    Article  CAS  Google Scholar 

36. Iwatani, M. et al. Troglitazone decreases serum uric acid concentrations in type II diabetic patients and non-diabetics. Diabetologia 43, 814–815 (2000).

    Article  CAS  Google Scholar 

37. Gokcel, A. et al. Evaluation of the safety and efficacy of sibutramine, orlistat and metformin in the treatment of obesity. Diabetes Obes. Metab. 4, 49–55 (2002).

    Article  CAS  Google Scholar 

38. Seber, S., Ucak, S., Basat, O. & Altuntas, Y. The effect of dual PPARα/γ stimulation with combination of rosiglitazone and fenofibrate on metabolic parameters in type 2 diabetic patients. Diabetes Res. Clin. Pract. 71, 52–58 (2006).

    Article  CAS  Google Scholar 

39. Tsouli, S.G., Liberopoulos, E.N., Mikhailidis, D.P., Athyros, V.G. & Elisaf, M.S. Elevated serum uric acid levels in metabolic syndrome: an active component or an innocent bystander? Metabolism 55, 1293–1301 (2006).

    Article  CAS  Google Scholar 

40. Rizos, C.V., Liberopoulos, E.N., Mikhailidis, D.P. & Elisaf, M.S. Pleiotropic effects of thiazolidinediones. Expert Opin. Pharmacother. 9, 1087–1108 (2008).

    Article  CAS  Google Scholar 

41. Sulem, P. et al. Identification of low-frequency variants associated with gout and serum uric acid levels. Nat. Genet. 43, 1127–1130 (2011).

    Article  CAS  Google Scholar 

42. The ARIC Investigators. The Atherosclerosis Risk in Communities (ARIC) Study: design and objectives. Am. J. Epidemiol. 129, 687–702 (1989).

43. Park, J.H. et al. Estimation of effect size distribution from genome-wide association studies and implications for future discoveries. Nat. Genet. 42, 570–575 (2010).

    Article  CAS  Google Scholar 

44. Yang, J., Lee, S.H., Goddard, M.E. & Visscher, P.M. GCTA: a tool for genome-wide complex trait analysis. Am. J. Hum. Genet. 88, 76–82 (2011).

    Article  CAS  Google Scholar 

45. Fuchsberger, C., Taliun, D., Pramstaller, P.P. & Pattaro, C. GWAtoolbox: an R package for fast quality control and handling of genome-wide association studies meta-analysis data. Bioinformatics 28, 444–445 (2012).

    Article  CAS  Google Scholar 

46. Willer, C.J., Li, Y. & Abecasis, G.R. METAL: fast and efficient meta-analysis of genomewide association scans. Bioinformatics 26, 2190–2191 (2010).

    Article  CAS  Google Scholar 

47. Pe'er, I., Yelensky, R., Altshuler, D. & Daly, M.J. Estimation of the multiple testing burden for genomewide association studies of nearly all common variants. Genet. Epidemiol. 32, 381–385 (2008).

    Article  Google Scholar 

48. Purcell, S. et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet. 81, 559–575 (2007).

    Article  CAS  Google Scholar 

49. Storey, J.D. & Tibshirani, R. Statistical significance for genomewide studies. Proc. Natl. Acad. Sci. USA 100, 9440–9445 (2003).

    Article  CAS  Google Scholar 

Download references

Author notes

1. Anna Köttgen, Eva Albrecht, Alexander Teumer, Veronique Vitart, Jan Krumsiek, Marina Ciullo, Caroline S Fox, Mark Caulfield, Murielle Bochud and Christian Gieger: These authors contributed equally to this work.

2. Marina Ciullo, Caroline S Fox, Mark Caulfield, Murielle Bochud and Christian Gieger: These authors jointly directed this work.

Authors and 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. Department of Life and Reproduction Sciences, Biology and Genetics Section, 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. Department of Biomedical Engineering, Chair of Medical Physics, 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. LifeLines Department, University Medical Center Groningen, 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. Department of Medicine, Channing Laboratory, 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

LifeLines Cohort Study

CARDIoGRAM Consortium

DIAGRAM Consortium

ICBP Consortium

MAGIC Consortium

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.

Corresponding authors

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

Competing interests

The authors declare no competing financial interests.

A list of contributing members appears in the Supplementary Note.

A list of contributing members appears in the Supplementary Note.

A list of contributing members appears in the Supplementary Note.

A list of contributing members appears in the Supplementary Note.

A list of contributing members appears in the Supplementary Note.

Cite this article

Köttgen, A., Albrecht, E., Teumer, A. et al. Genome-wide association analyses identify 18 new loci associated with serum urate concentrations. Nat Genet 45, 145–154 (2013). https://doi.org/10.1038/ng.2500

Download citation

• Received: 28 March 2012

• Accepted: 27 November 2012

• Published: 23 December 2012

• Issue Date: February 2013

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