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Genetic loci influencing kidney function and chronic kidney disease

Nature Genetics volume 42, pages 373375 (2010) | Download Citation

Abstract

Using genome-wide association, we identify common variants at 2p12–p13, 6q26, 17q23 and 19q13 associated with serum creatinine, a marker of kidney function (P = 10−10 to 10−15). Of these, rs10206899 (near NAT8, 2p12–p13) and rs4805834 (near SLC7A9, 19q13) were also associated with chronic kidney disease (P = 5.0 × 10−5 and P = 3.6 × 10−4, respectively). Our findings provide insight into metabolic, solute and drug-transport pathways underlying susceptibility to chronic kidney disease.

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Acknowledgements

Study-specific acknowledgments are provided in the Supplementary Note. We thank S. Asquith and J. Collier at K-bioscience for their help with the replication genotyping.

Author information

Author notes

    • John C Chambers
    • , Weihua Zhang
    • , Liz Lightstone
    • , James Scott
    • , Gerjan Navis
    • , Paul Elliott
    •  & Jaspal S Kooner

    These authors contributed equally to the work.

Affiliations

  1. Department of Epidemiology and Biostatistics, School of Public Health, Imperial College of London, London, UK.

    • John C Chambers
    • , Weihua Zhang
    • , Marjo-Riitta Jarvelin
    •  & Paul Elliott
  2. Ealing Hospital National Health Service (NHS) Trust, Middlesex, UK.

    • John C Chambers
    • , Weihua Zhang
    • , Joban S Sehmi
    • , Ranil de Silva
    •  & Jaspal S Kooner
  3. Department of Nephrology and Transplantation, King's College London, UK.

    • Graham M Lord
    • , Maria Hernandez-Fuentes
    •  & Esperanza Perucha
  4. Medical Research Council (MRC) Centre for Transplantation, King's College London, UK.

    • Graham M Lord
    • , Maria Hernandez-Fuentes
    •  & Esperanza Perucha
  5. National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre, Guy's and St. Thomas' NHS Foundation Trust and King's College London, London, UK.

    • Graham M Lord
    • , Maria Hernandez-Fuentes
    •  & Esperanza Perucha
  6. University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

    • Pim van der Harst
    • , Stephan J L Bakker
    • , Henk J G Bilo
    •  & Gerjan Navis
  7. MRC Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, UK.

    • Debbie A Lawlor
    •  & George Davey Smith
  8. National Heart and Lung Institute, Hammersmith Hospital Campus, Imperial College London, London, UK.

    • Joban S Sehmi
    • , Ranil de Silva
    • , James Scott
    •  & Jaspal S Kooner
  9. Division of Medicine, University College London, London, UK.

    • Daniel P Gale
    •  & Patrick H Maxwell
  10. Structural Bioinformatics Group, Imperial College London, London, UK.

    • Mark N Wass
    •  & Michael J E Sternberg
  11. Twin Research and Genetic Epidemiology Department, King's College London, St. Thomas' Hospital Campus, London, UK.

    • Kourosh R Ahmadi
    • , Ioana Cotlarciuc
    • , Nicole Soranzo
    •  & Timothy D Spector
  12. Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland.

    • Jacqui Beckmann
  13. University Institute of Social and Preventive Medicine, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.

    • Murielle Bochud
  14. Clinical Pharmacology Unit, University of Cambridge, Addenbrookes Hospital, Cambridge, UK.

    • Morris J Brown
  15. Clinical Pharmacology and The Genome Centre, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, London, UK.

    • Mark J Caulfield
    •  & Patricia B Munroe
  16. Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.

    • John M C Connell
    •  & Anna Dominiczak
  17. Department of Histopathology, Imperial College, Hammersmith Hospital, London, UK.

    • H Terence Cook
  18. Department of Gastroenterology and Hepatology, Imperial College London, London, UK.

    • Guohong Deng
  19. Division of Nephrology, Université Catholique de Louvain Medical School, Brussels, Belgium.

    • Olivier Devuyst
    •  & Céline Maréchal
  20. Isala Clinics, Zwolle, The Netherlands.

    • Lambert D Dikkeschei
  21. Center for Renal Diseases, Zvezdara University Medical Center, Belgrade, Serbia.

    • Nada Dimkovic
  22. South West Thames Institute for Renal Research, Epsom and St. Helier University Hospitals NHS Trust, Carshalton, UK.

    • Mark Dockrell
    •  & Marta Lapsley
  23. London School of Hygiene and Tropical Medicine, London, UK.

    • Shah Ebrahim
  24. Department of Human Genetics, Rheinisch-Westfaelische Technische Hochschule University Hospital Aachen, Aachen, Germany.

    • Thomas Eggermann
    •  & Klaus Zerres
  25. Cardiovascular Medicine, University of Oxford, Wellcome Trust Centre for Human Genetics, Oxford, UK.

    • Martin Farrall
  26. National Institute of Aging, Clinical Research Branch–Longitudinal Studies Section, Baltimore, Maryland, USA.

    • Luigi Ferrucci
    •  & Toshiko Tanaka
  27. Department of Nephrology and Clinical Immunology, RWTH University Hospital Aachen, Aachen, Germany.

    • Jurgen Floege
    •  & Georg Schlieper
  28. MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.

    • Nita G Forouhi
    • , Ruth J F Loos
    • , Jian'an Luan
    •  & Nicholas J Wareham
  29. Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

    • Ron T Gansevoort
    •  & Marc A J Seelen
  30. Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA.

    • Xijin Han
    • , Yun Li
    •  & Goncalo R Abecasis
  31. Department of Clinical Sciences, Lund University, Malmö, Sweden.

    • Bo Hedblad
    • , Olle Melander
    •  & Marketa Sjögren
  32. Department of Nephrology, University Medical Center Groningen, Groningen, The Netherlands.

    • Jaap J Homan van der Heide
  33. Department of Transplantation Immunology, University Medical Center Groningen, Groningen, The Netherlands.

    • Bouke G Hepkema
  34. Centre of Epidemiology for Child Health, University College London Institute of Child Health, London, UK.

    • Elina Hypponen
  35. Department of Medical Genetics, University of Lausanne and the Swiss Institute of Bioinformatics, Lausanne, Switzerland.

    • Toby Johnson
  36. Langerhans Medical Research Group, Zwolle, The Netherlands.

    • Paul E de Jong
    •  & Nanne Kleefstra
  37. Unit of Genetic Epidemiology and Bioinformatics, Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

    • Vasiliki Lagou
    •  & Harold Snieder
  38. Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.

    • Karin Luttropp
    •  & Louise Nordfors
  39. Division of Nephrology, University of Maryland School of Medicine, Baltimore, Maryland, USA.

    • Afshin Parsa
  40. Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.

    • Leena Peltonen
  41. Institute for Molecular Medicine Finland (FIMM), Nordic European Molecular Biology Laboratory (EMBL) Partnership for Molecular Medicine, Biomedicum Helsinki 2U and University of Helsinki, Helsinki, Finland.

    • Leena Peltonen
  42. National Institute for Health and Welfare, Helsinki, Finland.

    • Leena Peltonen
    • , Anneli Pouta
    •  & Marjo-Riitta Jarvelin
  43. Department of Psychiatry, Institute for Research in Extramural Medicine (EMGO), Neuroscience Campus, Vrije Universiteit (VU) Medical Center, Amsterdam, The Netherlands.

    • Brenda W Penninx
    •  & Johannes H Smit
  44. Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands.

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

    • Brenda W Penninx
    •  & Johannes H Smit
  46. Institute of Health Sciences, University of Oulu, Oulu, Finland.

    • Anneli Pouta
    •  & Marjo-Riitta Jarvelin
  47. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.

    • Inga Prokopenko
    •  & Mark I McCarthy
  48. Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford, UK.

    • Inga Prokopenko
    •  & Mark I McCarthy
  49. Oxford NIHR Biomedical Research Centre, Oxford, UK.

    • Inga Prokopenko
    •  & Mark I McCarthy
  50. University of Southampton, Southampton, UK.

    • Paul J Roderick
  51. Institute of Clinical Medicine, Department of Clinical Chemistry, University of Oulu, Oulu, Finland.

    • Aimo Ruokonen
  52. Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, UK.

    • Nilesh J Samani
  53. Istituto di Neurogenetica e Neurofarmacologia, Consiglio Nazionale delle Ricerche, Cagliari, Italy.

    • Serena Sanna
    •  & Manuela Uda
  54. Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.

    • Martin Schalling
  55. Laboratory of Genetics, US National Institutes of Health Biomedical Research Center, National Institute on Aging, Baltimore, Maryland, USA.

    • David Schlessinger
  56. Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland, USA.

    • Alan R Shuldiner
  57. Division of Renal Medicine K56, Karolinska University Hospital at Huddinge, Stockholm, Sweden.

    • Peter Stenvinkel
  58. Chemical Pathology, Guy's and St Thomas' Hospitals Trust, London, UK.

    • Ramasamyiyer Swaminathan
  59. General Practice 't Veen, Hattem, The Netherlands.

    • Lielith J Ubink-Veltmaat
  60. Department of Internal Medicine, University Hospital Center, University of Lausanne, Lausanne, Switzerland.

    • Peter Vollenweider
    •  & Gerard Waeber
  61. Cambridge Institute for Medical Research, Addenbrooke's Hospital, Hills Road, Cambridge, UK.

    • Chris Wallace
  62. Medical Genetics, Clinical Pharmacology and Discovery Medicine, GlaxoSmithKline, King of Prussia, Pennsylvania, USA.

    • Dawn Waterworth
    •  & Vincent Mooser
  63. Biocenter Oulu, University of Oulu, Oulu, Finland.

    • Marjo-Riitta Jarvelin
  64. Renal Section, Division of Medicine, Hammersmith Hospital Campus, Imperial College London, London, UK.

    • Liz Lightstone
  65. MRC-HPA Centre for Environment and Health, Department of Epidemiology and Public Health, Imperial College of London, London, UK.

    • Paul Elliott

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Contributions

J.C.C., P.E., L.L., J.S., G.N. and J.S.K. designed the study. J.C.C., W.Z., D.A.L. and P.v.d.H. led the data analysis. J.C.C., P.E., L.L., J.S., G.N. and J.S.K. wrote the manuscript, with contributions from all the authors.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to John C Chambers or Jaspal S Kooner.

Supplementary information

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    Supplementary Text and Figures

    Supplementary Methods, Supplementary Note, Supplementary Tables 1–6 and Supplementary Figures 1–6

About this article

Publication history

Received

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DOI

https://doi.org/10.1038/ng.566

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