Article | Published:

New loci associated with kidney function and chronic kidney disease

Nature Genetics volume 42, pages 376384 (2010) | Download Citation


Chronic kidney disease (CKD) is a significant public health problem, and recent genetic studies have identified common CKD susceptibility variants. The CKDGen consortium performed a meta-analysis of genome-wide association data in 67,093 individuals of European ancestry from 20 predominantly population-based studies in order to identify new susceptibility loci for reduced renal function as estimated by serum creatinine (eGFRcrea), serum cystatin c (eGFRcys) and CKD (eGFRcrea < 60 ml/min/1.73 m2; n = 5,807 individuals with CKD (cases)). Follow-up of the 23 new genome-wide–significant loci (P < 5 × 10−8) in 22,982 replication samples identified 13 new loci affecting renal function and CKD (in or near LASS2, GCKR, ALMS1, TFDP2, DAB2, SLC34A1, VEGFA, PRKAG2, PIP5K1B, ATXN2, DACH1, UBE2Q2 and SLC7A9) and 7 loci suspected to affect creatinine production and secretion (CPS1, SLC22A2, TMEM60, WDR37, SLC6A13, WDR72 and BCAS3). These results further our understanding of the biologic mechanisms of kidney function by identifying loci that potentially influence nephrogenesis, podocyte function, angiogenesis, solute transport and metabolic functions of the kidney.

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We thank all participants and the study staff of the Age, Gene/Environment Susceptibility Reykjavik Study (AGES); the Amish Study; the Atherosclerosis Risk in Communities Study (ARIC); the Austrian Stroke Prevention study (ASPS); the Baltimore Longitudinal Study of Aging (BLSA); the Cardiovascular Health Study (CHS); the Erasmus Rucphen Family (ERF) study; the Family Heart Study (FamHS); the Framingham Heart Study (FHS); the Genetic Epidemiology Network of Atherosclerosis (GENOA); the Gutenberg Heart Study; the Health, Aging and Body Composition (HABC) study; the Health Professionals Follow-Up Study (HPFS); the Kooperative Gesundheitsforschung in der Region Augsburg (KORA); the Korcula Study; the Micros Study; the Nurses' Health Study (NHS); the Northern Swedish Population Health Study (NSPHS); the Orkney Complex Disease Study (Orcades); the PopGen Study; the Rotterdam Study (RS); the Swiss Cohort Study on Air Pollution and Lung Diseases in Adults (SAPALDIA); the Salzburg Atherosclerosis Prevention program in subjects at High Individual Risk (SAPHIR); the Study of Health in Pomerania (SHIP); the Sorbs Study; the Split Study; the Vis Study; and the Women's Genome Health Study (WGHS), as well as the Cohorts for Heart and Aging Research in Genome Epidemiology (CHARGE) Consortium, for their invaluable contributions. A detailed list of acknowledgments and funding sources can be found in the Supplementary Note.

Author information

Author notes

    • Anna Köttgen
    • , Cristian Pattaro
    • , Carsten A Böger
    •  & Christian Fuchsberger

    These authors contributed equally to this work.

    • Daniel I Chasman
    • , W H Kao
    • , Iris M Heid
    •  & Caroline S Fox

    These authors jointly directed this work.


  1. Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland, USA.

    • Anna Köttgen
    • , Man Li
    • , Josef Coresh
    •  & W H Kao
  2. Renal Division, University Hospital of Freiburg, Freiburg, Germany.

    • Anna Köttgen
  3. Institute of Genetic Medicine, European Academy Bozen/Bolzano (EURAC), Bolzano, Italy.

    • Cristian Pattaro
    • , Christian Fuchsberger
    • , Cosetta Minelli
    •  & Peter P Pramstaller
  4. Affiliated Institute of the University of Lübeck, Germany, Viale Druso, Bolzano, Italy.

    • Cristian Pattaro
    • , Christian Fuchsberger
    • , Cosetta Minelli
    •  & Peter P Pramstaller
  5. Department of Internal Medicine II, University Medical Center Regensburg, Regensburg, Germany.

    • Carsten A Böger
    •  & Matthias Olden
  6. Department of Epidemiology and Preventive Medicine, University Medical Center Regensburg, Regensburg, Germany.

    • Matthias Olden
    •  & Iris M Heid
  7. Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, USA.

    • Nicole L Glazer
  8. Department of Medicine, University of Washington, Seattle, Washington, USA.

    • Nicole L Glazer
    •  & David Siscovick
  9. University of Maryland Medical School, Baltimore, Maryland, USA.

    • Afshin Parsa
    • , Jeffrey R O'Connell
    • , Braxton D Mitchell
    •  & Alan R Shuldiner
  10. Division of Statistical Genomics, Washington University School of Medicine, St. Louis, Missouri, USA.

    • Xiaoyi Gao
    • , Shamika Ketkar
    • , Mary Feitosa
    • , Michael Province
    •  & Ingrid Borecki
  11. Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.

    • Qiong Yang
  12. Icelandic Heart Association, Kopavogur, Iceland.

    • Albert V Smith
    • , Thor Aspelund
    • , Gudny Eiriksdottir
    •  & Vilmundur Gudnason
  13. University of Iceland, Reykjavik, Iceland.

    • Albert V Smith
    • , Thor Aspelund
    •  & Vilmundur Gudnason
  14. Department of Neurogeriatrics, Austrian Stroke Prevention Study, Institute of Molecular Biology and Biochemistry and University Clinic of Neurology, Medical University Graz, Graz, Austria.

    • Helena Schmidt
  15. Clinical Research Branch, National Institute on Aging, Baltimore, Maryland, USA.

    • Toshiko Tanaka
  16. Medstar Research Institute, Baltimore, Maryland, USA.

    • Toshiko Tanaka
  17. Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.

    • Aaron Isaacs
    • , Abbas Dehghan
    • , Ben A Oostra
    • , Yurii S Aulchenko
    • , Janine F Felix
    • , Fernando Rivadeneira
    • , Andre G Uitterlinden
    • , Albert Hofman
    • , Cornelia M van Duijn
    •  & Jacqueline C Witteman
  18. The National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA.

    • Shih-Jen Hwang
    • , Andrew D Johnson
    •  & Caroline S Fox
  19. Center for Population Studies, Framingham, Massachusetts, USA.

    • Shih-Jen Hwang
    • , Andrew D Johnson
    •  & Caroline S Fox
  20. Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands.

    • Abbas Dehghan
    • , M Carola Zillikens
    • , Yurii S Aulchenko
    • , Janine F Felix
    • , Fernando Rivadeneira
    • , Andre G Uitterlinden
    • , Albert Hofman
    • , Cornelia M van Duijn
    •  & Jacqueline C Witteman
  21. Interfaculty Institute for Genetics and Functional Genomics, Ernst-Moritz-Arndt University Greifswald, Greifswald, Germany.

    • Alexander Teumer
    •  & Uwe Völker
  22. Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.

    • Guillaume Paré
  23. Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, USA.

    • Elizabeth J Atkinson
    •  & Mariza de Andrade
  24. Department of Medicine II, University Medical Center Mainz, Mainz, Germany.

    • Tanja Zeller
    • , Philipp S Wild
    • , Renate B Schnabel
    • , Sandra Wilde
    • , Thomas F Munzel
    •  & Stefan Blankenberg
  25. Department of Biostatistical Sciences, Wake Forest University, Division of Public Health Sciences, Winston-Salem, North Carolina, USA.

    • Kurt Lohman
  26. Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA.

    • Marilyn C Cornelis
    •  & Frank B Hu
  27. Swiss Tropical and Public Health Institute, Basel, Switzerland.

    • Nicole M Probst-Hensch
    •  & Medea Imboden
  28. University of Basel, Basel, Switzerland.

    • Nicole M Probst-Hensch
    •  & Medea Imboden
  29. Division of Genetic Epidemiology, Innsbruck Medical University, Innsbruck, Austria.

    • Florian Kronenberg
    • , Anita Brandstätter
    •  & Barbara Kollerits
  30. Department of Medicine, University of Leipzig, Leipzig, Germany.

    • Anke Tönjes
    • , Michael Stumvoll
    •  & Peter Kovacs
  31. Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, Scotland, UK.

    • Caroline Hayward
    • , Alan F Wright
    • , Susan Campbell
    • , Veronique Vitart
    •  & Nick Hastie
  32. Laboratory of Epidemiology, Demography and Biometry, National Institute on Aging, Bethesda, Maryland, USA.

    • Lenore J Launer
    •  & Tamara B Harris
  33. Miami Institute for Human Genomics, Miami, Florida, USA.

    • Evadnie Rampersaud
  34. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

    • Dan E Arking
  35. Human Genetics Center, University of Texas Health Science Center, Houston, Texas, USA.

    • Eric Boerwinkle
  36. Department of Epidemiology and Biostatistics, Department of Forensic Molecular Biology, Rotterdam, The Netherlands.

    • Maksim Struchalin
  37. Department of Neurogeriatrics, Austrian Stroke Prevention Study, University Clinic of Neurology, Medical University Graz, Graz, Austria.

    • Margherita Cavalieri
    •  & Reinhold Schmidt
  38. Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA.

    • Andrew Singleton
  39. Clinical Research Branch, National Institute on Aging, Baltimore, Maryland, USA.

    • Francesco Giallauria
    • , Jeffrey Metter
    •  & Luigi Ferrucci
  40. Kidney Research Institute and Division of Nephrology, University of Washington, Seattle, Washington, USA.

    • Ian H de Boer
  41. Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.

    • Talin Haritunians
  42. Department of Biostatistics, University of Washington, Seattle, Washington, USA.

    • Thomas Lumley
  43. Department of Epidemiology, University of Washington, Seattle, Washington, USA.

    • David Siscovick
  44. Department of Medicine, Cardiovascular Health Research Unit, University of Washington and Group Health Research Institute, Seattle, Washington, USA.

    • Bruce M Psaty
  45. Department of Epidemiology, University of Washington and Group Health Research Institute, Seattle, Washington, USA.

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

    • Bruce M Psaty
  47. Department of Internal Medicine, Erasmus University, Rotterdam, The Netherlands.

    • M Carola Zillikens
    • , Fernando Rivadeneira
    •  & Andre G Uitterlinden
  48. Department of Internal Medicine,Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA.

    • Stephen T Turner
  49. Institute for Medical Biometry and Statistics, University at Lübeck, Lübeck University Hospital Schleswig-Holstein, Campus Lübeck, Germany.

    • Arne Schillert
    •  & Andreas Ziegler
  50. Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

    • Tennille S Leak
  51. Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.

    • Thomas Illig
    • , Norman Klopp
    • , Christa Meisinger
    • , H-Erich Wichmann
    •  & Iris M Heid
  52. Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany.

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

    • H-Erich Wichmann
  54. Zentrum für Innere Medizin, Klinik für Innere Medizin II–Kardiologie, Universitätsklinikum Ulm, Ulm, Germany.

    • Wolfgang Koenig
  55. Centre for Population Health Sciences, University of Edinburgh Medical School, Edinburgh, Scotland, UK.

    • Lina Zgaga
    • , Sarah H Wild
    • , Harry Campbell
    • , Igor Rudan
    •  & James F Wilson
  56. Croatian Centre for Global Health, University of Split Medical School, Split, Croatia.

    • Tatijana Zemunik
    • , Mladen Boban
    •  & Wei Wang
  57. Andrija Stampar School of Public Health, Medical School, University of Zagreb, Zagreb, Croatia.

    • Ivana Kolcic
    •  & Ozren Polasek
  58. Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.

    • Åsa Johansson
    • , Wilmar Igl
    • , Ghazal Zaboli
    •  & Ulf Gyllensten
  59. Institute of Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany.

    • David Ellinghaus
    • , Stefan Schreiber
    •  & Andre Franke
  60. Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK.

    • Dorothea Nitsch
  61. First Department of Internal Medicine, Paracelsus Medical University, Salzburg, Austria.

    • Lyudmyla Kedenko
    •  & Bernhard Paulweber
  62. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.

    • Reedik Mägi
    •  & Inga Prokopenko
  63. Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.

    • Reedik Mägi
    •  & Inga Prokopenko
  64. Institute of Anatomy and Cell Biology, Ernst-Moritz-Arndt University Greifswald, Greifswald, Germany.

    • Karlhans Endlich
  65. Institute for Community Medicine, Ernst-Moritz-Arndt University Greifswald, Greifswald, Germany.

    • Henry Völzke
  66. Institute of Pharmacology, Ernst-Moritz-Arndt University Greifswald, Greifswald, Germany.

    • Heyo K Kroemer
  67. Institute of Clinical Chemistry and Laboratory Medicine, Ernst-Moritz-Arndt University Greifswald, Greifswald, Germany.

    • Matthias Nauck
  68. Amgen, Cambridge, Massachusetts, USA.

    • Sunita Badola
    •  & Alexander N Parker
  69. Brigham and Women's Hospital, Boston, Massachusetts, USA.

    • Paul M Ridker
    •  & Daniel I Chasman
  70. Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, Michigan, USA.

    • Sharon L R Kardia
  71. Department of Epidemiology and Prevention, Wake Forest University, Division of Public Health Sciences, Winston-Salem, North Carolina, USA.

    • Yongmei Liu
  72. Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

    • Gary C Curhan
  73. University Hospitals of Geneva, Geneva, Switzerland.

    • Thierry Rochat
  74. School of Public Health and Family Medicine, Capital Medical University, Beijing, China.

    • Wei Wang
  75. Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, Maryland, USA.

    • Josef Coresh
    •  & W H Kao
  76. General Internal Medicine, University of California, San Francisco, San Francisco, California, USA.

    • Michael G Shlipak
  77. Department of Medicine V, Mannheim University Hospital, University of Heidelberg, Mannheim, Germany.

    • Bernhard K Krämer
  78. Institute of Physiology, Ernst-Moritz-Arndt University Greifswald, Greifswald, Germany.

    • Rainer Rettig
  79. Brigham and Women's Hospital Department of Endocrinology and Harvard Medical School, Boston, Massachusetts, USA.

    • Caroline S Fox


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Writing group: A.K., C.P., C.A.B., C.F., N.L.G., A.P., X.G., W.H.K., I.M.H., C.S.F.

Study design: L.J.L., T.B.H., V.G., A.P., E.B., J.C., A.K., L.F., J.M., N.L.G., T.L., D.S., B.M.P., M.G.S., B.A.O., C.M.v.D., I.B., M.P., C.S.F., Q.Y., S.K., M.d.A., E.J.A., Y.L., C.A.B., I.M.H., T.I., H.-E.W., N.K., C.M., I.R., P.P.P., F.B.H., G.C.C., U.G., J.F.W., S.H.W., A.F.W., H.C., A.H., N.M.P.-H., M.I., D.N., T.R., B.P., R.R., K.E., H.V., P.K., A.T., M.B., W.W., O.P., N.H., C.H., V.V., D.I.C., G.P., A.N.P., P.M.R., S.B., T.F.M.

Study management: G.E., L.J.L., T.B.H., V.G., A.P., B.D.M., A.R.S., E.B., J.C., W.H.K., J.M., D.S., B.M.P., M.G.S., A.I., M.C.Z., B.A.O., C.M.v.D., I.B., M.P., C.S.F., S.K., M.d.A., C.A.B., I.M.H., M.O., B.K., W.K., T.I., H.-E.W., C.M., I.R., L.Z., T.Z., C.P., C.F., P.P.P., M.C.C., F.B.H., G.C.C., A.J., G.Z., U.G., J.F.W., S.H.W., A.G.U., F.R., N.M.P.-H., M.I., T.R., B.K.K., L.K., B.P., F.K., R.R., K.E., H.V., M.S., A.T., M.B., O.P., N.H., C.H., V.V., D.I.C., G.P., S.B., A.N.P., P.M.R.

Subject recruitment: G.E., T.B.H., V.G., B.D.M., A.R.S., J.C., L.F., B.M.P., B.A.O., C.M.v.D., C.S.F., S.T.T., T.I., H.-E.W., I.R., L.Z., T.Z., I.K., P.P.P., A.J., J.F.W., S.H.W., S.S., A.D., J.C.W., N.M.P.-H., M.I., D.N., T.R., B.P., R.R., H.V., A.T., M.B., O.P., C.H., S.B., T.Z., R.S.

Interpretation of results: T.B.H., A.P., E.B., J.C., W.H.K., A.K., L.F., T.T., F.G., N.L.G., T.L., T.H., B.M.P., A.I., M.C.Z., B.A.O., C.M.v.D., I.B., M.P., X.G., C.S.F., Q.Y., S.-J.H., S.K., S.T.T., M.d.A., E.J.A., Y.L., T.S.L., C.A.B., I.M.H., M.O., B.K., W.K., I.R., T.Z., I.K., C.P., C.F., C.M., P.P.P., G.C.C., A.D.J., W.I., G.Z., U.G., J.F.W., S.H.W., A.D., Y.S.A., M.I., B.K., L.K., B.P., F.K., R.R., K.E., A.T., H.V., H.K.K., M.N., U.V., M.B., O.P., N.H., C.H., V.V., D.I.C., G.P., P.M.R.

Critical review of manuscript: All authors.

Statistical methods and analysis: A.V.S., T.A., V.G., J.R.O., E.R., A.K., M.L., R.S., H.S., T.T., N.L.G., T.L., B.M.P., A.I., X.G., M.F., C.S.F., Q.Y., S.J.H., S.K., M.d.A., E.J.A., K.L., Y.L., C.A.B., I.M.H., M.O., N.K., C.P., C.F., C.M., M.C.C., A.J., W.I., D.E., A.F., A.D., F.R., Y.S.A., N.M.P.-H., B.K., F.K., A.T., U.V., R.M., I.P., C.H., V.V., D.I.C., G.P., A.Z., A.B., S.W., J.F.F., D.E.A.

Genotyping: E.B., R.S., H.S., L.F., T.H., A.I., B.A.O., C.M.v.D., M.d.A., Y.L., T.I., H.-E.W., C.M., J.F.W., H.C., A.F., A.G.U., F.R., M.I., F.K., H.K.K., M.N., U.V., M.S., S.C., C.H., S.B., A.N.P., A.B., N.K.

Bioinformatics: A.V.S., T.A., J.R.O., M.S., M.C., T.T., A.I., B.A.O., C.M.v.D., Q.Y., A.D.J., E.J.A., Y.L., C.A.B., I.M.H., M.O., C.P., C.F., M.C.C., A.J., W.I., D.E., A.D., F.R., Y.S.A., F.K., A.T., H.K.K., U.V., D.I.C., G.P., D.E.A.

Competing interests

C.A.B. has received lecture fees from Novartis Deutschland GmbH, Fresenius Medical Care Deutschland GmbH and Sandoz Pharmaceuticals GmbH. S.B. and A.N.P. are employees of Amgen.

Corresponding authors

Correspondence to Daniel I Chasman or W H Kao or Iris M Heid or Caroline S Fox.

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    Supplementary Note, Supplementary Tables 1–7 and Supplementary Figures 1 and 2

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