TY - JOUR
KW - Humans
KW - Gene Expression Regulation
KW - Genetic Predisposition to Disease
KW - Genome-Wide Association Study
KW - Genotype
KW - Renal Insufficiency, Chronic/ genetics
AU - Yang Q.
AU - Hu F.
AU - Wang J.
AU - Chasman D.
AU - Koenig W.
AU - Kleber M.
AU - Hofman A.
AU - Wilson J.
AU - Gudnason V.
AU - Harris T.
AU - Ridker P.
AU - Muntner P.
AU - Rochtchina E.
AU - Salvi E.
AU - Bochud M.
AU - Munroe P.
AU - Cusi D.
AU - Kao W.
AU - Isaacs A.
AU - van Duijn C.
AU - Uitterlinden A.
AU - Kronenberg F.
AU - Stengel B.
AU - Woodward Mark
AU - Fox C.
AU - Katz R.
AU - Li M.
AU - Smith J.
AU - Jacobs G.
AU - Chen M.
AU - Ford I.
AU - Kahonen M.
AU - Lehtimaki T.
AU - Viikari J.
AU - Eiriksdottir G.
AU - Hamet P.
AU - Li Y.
AU - Coresh J.
AU - Gorski M.
AU - Tin A.
AU - Garnaas M.
AU - Chu A.
AU - Pattaro C.
AU - Teumer A.
AU - Tremblay J.
AU - Aspelund T.
AU - Launer L.
AU - Smith A.
AU - Mitchell B.
AU - O'Connell J.
AU - Shuldiner A.
AU - Schmidt H.
AU - Schmidt R.
AU - Holliday E.
AU - Mitchell P.
AU - de Boer I.
AU - Li G.
AU - Siscovick D.
AU - Hwang S.
AU - Olden M.
AU - de Andrade M.
AU - Atkinson E.
AU - Kardia S.
AU - Turner S.
AU - Stafford J.
AU - Ding J.
AU - Liu Y.
AU - Grallert H.
AU - Meisinger C.
AU - Kramer B.
AU - Kramer H.
AU - Rosas S.
AU - Nolte I.
AU - Penninx B.
AU - Snieder H.
AU - Franke A.
AU - Lieb W.
AU - Dehghan A.
AU - Franco O.
AU - Rivadeneira F.
AU - Sedaghat S.
AU - Coassin S.
AU - Haun M.
AU - Kollerits B.
AU - Paulweber B.
AU - Endlich K.
AU - Volker U.
AU - Rettig R.
AU - Chouraki V.
AU - Helmer C.
AU - Lambert J.
AU - Metzger M.
AU - Lyytikainen L.
AU - Raitakari O.
AU - Parsa A.
AU - Heid I.
AU - Goessling W.
AU - Kottgen A.
AU - Boger C.
AU - Lu Y.
AU - Tanaka T.
AU - Brenner H.
AU - Rao M.
AU - Sorice R.
AU - Mijatovic V.
AU - Ko Y.
AU - Taliun D.
AU - Fuchsberger C.
AU - Dieffenbach A.
AU - Lupo A.
AU - Ponte B.
AU - Hayward C.
AU - Gieger C.
AU - Shaffer C.
AU - Muller C.
AU - Ackermann D.
AU - Boerwinkle E.
AU - Ehret G.
AU - Homuth G.
AU - Gambaro G.
AU - Malerba G.
AU - Wichmann H.
AU - Wallaschofski H.
AU - Volzke H.
AU - Leach I.
AU - Rudan I.
AU - Denny J.
AU - Butterbach K.
AU - Ferrucci L.
AU - Kedenko L.
AU - Nauck M.
AU - Waldenberger M.
AU - Pruijm M.
AU - Rheinberger M.
AU - Verweij N.
AU - Soranzo N.
AU - Polasek O.
AU - Pramstaller P.
AU - Wild P.
AU - Biffar R.
AU - Carroll R.
AU - Loos R.
AU - Stracke S.
AU - Zeller T.
AU - Illig T.
AU - Devuyst O.
AU - Susztak K.
AU - Peralta C.
AU - Foster M.
AU - Pers T.
AU - Johnson A.
AU - Tayo B.
AU - Nalls M.
AU - Feitosa M.
AU - d'Adamo P.
AU - Adeyemo A.
AU - Zonderman A.
AU - van der Most P.
AU - Wright A.
AU - Morrison A.
AU - Dreisbach A.
AU - Metspalu A.
AU - Tonjes A.
AU - Robino A.
AU - Johansson A.
AU - Demirkan A.
AU - Freedman B.
AU - Oostra B.
AU - Buckley B.
AU - Rotimi C.
AU - Sala C.
AU - Saint-Pierre A.
AU - Shriner D.
AU - Ruggiero D.
AU - Toniolo D.
AU - Czamara D.
AU - Ellinghaus D.
AU - Ruderfer D.
AU - Bottinger E.
AU - Murgia F.
AU - Ernst F.
AU - Navis G.
AU - Curhan G.
AU - Thun G.
AU - Pistis G.
AU - Montgomery G.
AU - Campbell H.
AU - Kroemer H.
AU - Lin H.
AU - Guessous I.
AU - Prokopenko I.
AU - Borecki I.
AU - Kolcic I.
AU - Persico I.
AU - Jukema J.
AU - Felix J.
AU - Divers J.
AU - Gaspoz J.
AU - Faul J.
AU - Hirschhorn J.
AU - Attia J.
AU - Whitfield J.
AU - Karjalainen J.
AU - Fernandes J.
AU - Keene K.
AU - Lohman K.
AU - Portas L.
AU - Yengo L.
AU - Franke L.
AU - Rose L.
AU - Struchalin M.
AU - Cavalieri M.
AU - Cornelis M.
AU - Ciullo M.
AU - Pirastu M.
AU - McEvoy M.
AU - Adam M.
AU - Cocca M.
AU - Imboden M.
AU - Stumvoll M.
AU - Evans M.
AU - Sale M.
AU - Boban M.
AU - Bouatia-Naji N.
AU - Martin N.
AU - Hastie N.
AU - Probst-Hensch N.
AU - Gottesman O.
AU - Gasparini P.
AU - Smit J.
AU - Kovacs P.
AU - Froguel P.
AU - Magi R.
AU - Middelberg R.
AU - Scott R.
AU - Wild S.
AU - Ulivi S.
AU - Enroth S.
AU - Kloiber S.
AU - Trompet S.
AU - Hancock S.
AU - Zemunik T.
AU - Nikopensius T.
AU - Esko T.
AU - Gyllensten U.
AU - Emilsson V.
AU - Vitart V.
AU - Aalto V.
AU - Chen W.
AU - Igl W.
AU - Marz W.
AU - Chalmers J.
AB - Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
AD - Center for Biomedicine, European Academy of Bozen/Bolzano (EURAC), affiliated to the University of Lubeck, Via Galvani 31, Bolzano 39100, Italy.<br/>Interfaculty Institute for Genetics and Functional Genomics, Ernst-Moritz-Arndt-University Greifswald, Friedrich-Loeffler-Strasse 15a, Greifswald 17487, Germany.<br/>Institute for Community Medicine, University of Greifswald, Walther-Rathenau-Strasse 48, Greifswald 17487, Germany.<br/>Department of Genetic Epidemiology, Institute of Epidemiology and Preventive Medicine, University of Regensburg, Franz-Josef-Strauss-Allee 11, Regensburg 93053, Germany.<br/>Department of Nephrology, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, Regensburg 93053, Germany.<br/>Preventive Medicine, Brigham and Women's Hospital, 900 Commonwealth Avenue East, Boston, Massachusetts 02215, USA.<br/>Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, Maryland 21205, USA.<br/>Department of Life and Reproduction Sciences, University of Verona, Strada Le Grazie 8, Verona 37134, Italy.<br/>Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, New Research Building77 Avenue Louis Pasteur, Room 458, Boston, Massachusetts 02115, USA.<br/>Institute of Genetics and Biophysics "Adriano Buzzati-Traverso"-CNR, Via P. Castellino 111, Napoli 80131, Italy.<br/>Department of Internal Medicine IV, University Hospital Freiburg, Berliner Allee 29, Freiburg 79110, Germany.<br/>Division of Nephrology/Tufts Evidence Practice Center, Tufts University School of Medicine, Tufts Medical Center, Boston, Massachusetts 02111, USA.<br/>Department of Biostatistics, Boston University School of Public Health, 715 Albany Street, Boston, Massachusetts 02118, USA.<br/>Department of Neurology, Boston University School of Medicine, 72 East Concord ST B603, Boston, Massachusetts 02118, USA.<br/>Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children's Hospital, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.<br/>Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 2142, USA.<br/>NHLBI's Framingham Heart Study and the Center for Population Studies, 73 Mt Wayte Avenue, Suite 2, Framingham, Massachusetts 01702, USA.<br/>Renal Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, 415 Curie Boulevard, 405B Clinical Research Building, Philadelphia, Pennsylvania 19104-4539, USA.<br/>Department of Public Health Sciences, Loyola Medical Center, 2160 S First Avenue, Maywood, Illinois 60153, USA.<br/>Laboratory of Neurogenetics, Building 35-Porter Building, 1A1015, National Institute on Aging/NIH, Bethesda, Maryland 20892, USA.<br/>Division of Statistical Genomics, Washington University School of Medicine, 4444 Forest Park Boulevard, Box 8506, St Louis, Missouri 63108, USA.<br/>Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Dr Molewaterplein 50, PO Box 2040, Rotterdam 3000 CA, The Netherlands.<br/>Centre for Medical Systems Biology Leiden, Dr Molewaterplein 50, PO Box 2040, Rotterdam 3000 CA, The Netherlands.<br/>Department of Epidemiology, Erasmus University Medical Center, PO Box 2040, Rotterdam 3000 CA, The Netherlands.<br/>Institute for Maternal and Child Health-IRCCS "Burlo Garofolo" and University of Trieste, via dell'Istria 65/1, Trieste 34137, Italy.<br/>Center for Research on Genomics and Global Health, National Human Genome Research Institute, Building 12A, Room 4047, 12 South Dr, MSC 5635, Bethesda, Maryland 20892-5635, USA.<br/>Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, Heidelberg 69120, Germany.<br/>German Cancer Consortium (DKTK), Im Neuenheimer Feld 581, Heidelberg 69120, Germany.<br/>Laboratory of Personality and Cognition, National Institute on Aging, National Institutes of Health, NIH Biomedical Center, 251 Bayview Boulevard, Suite 100, Baltimore, Maryland 21224, USA.<br/>Unit of Genetic Epidemiology and Bioinformatics, Department of Epidemiology, University Medical Center Groningen, PO Box 30001, Groningen 9700 RB, The Netherlands.<br/>MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road, Edinburgh EH4 2XU, UK.<br/>Department of Medicine, University of Maryland School of Medicine, 685 West Baltimore Street, Baltimore, Maryland 21201, USA.<br/>Geriatric Research and Education Clinical Center, Veterans Administration Medical Center, 10 North Greene Street, Baltimore, Maryland 21201, USA.<br/>Human Genetics Center, University of Texas Health Science Center at Houston, 1200 Pressler St Suite 453E, Houston, Texas 77030, USA.<br/>Icelandic Heart Association, Research Institute, Holtasmari 1, Kopavogur 201, Iceland.<br/>University of Iceland, Saemundargotu 2, Reykjavik 101, Iceland.<br/>Division of Nephrology, University of Mississippi, 2500 North State Street, Jackson, Mississippi 39216, USA.<br/>Institute of Clinical Molecular Biology, Christian-Albrechts University of Kiel, Schittenhelmstrasse 12, Kiel 24105, Germany.<br/>Department of Internal Medicine, Erasmus University Medical Center, PO Box 1738, Rotterdam 3000 DR, The Netherlands.<br/>Estonian Genome Center of University of Tartu (EGCUT), Riia 23B, Tartu 51010, Estonia.<br/>Institute of Molecular and Cell Biology, University of Tartu and Estonian Biocenter, Riia 23, Tartu 51010, Estonia.<br/>Department of Medicine, University of Leipzig, Liebigstrasse 18, Leipzig 04103, Germany.<br/>Division of Nephrology, Department of Medicine, University of Verona, Piazzale Aristide Stefani 1, Verona 37126, Italy.<br/>Uppsala University, Department of Immunology, Genetics and Pathology, Biomedical Center, SciLifeLab, Uppsala University, Uppsala SE- 75108, Sweden.<br/>Innsbruck Medical University, Division of Genetic Epidemiology, Schoepfstrasse 41, Innsbruck 6020, Austria.<br/>Internal Medicine Department, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157-1053, USA.<br/>Nephrology Division, Department of Specialties of Internal Medicine, Geneva University Hospital, 4 rue Gabrielle-Perret-Gentil, Geneve 1211, Switzerland.<br/>Department of Clinical Genetics, Erasmus University Medical Center, Dr Molewaterplein 50, PO Box 2040, Rotterdam 3000 CA, The Netherlands.<br/>First Department of Internal Medicine, Paracelsus Medical University/Salzburger Landeskliniken, Mullner Hauptstrasse 48, Salzburg 5020, Austria.<br/>University Medical Centre Mannheim, 5th Department of Medicine, University of Heidelberg, Theodor Kutzer Ufer 1-3, Mannheim 68167, Germany.<br/>Department of Pharmacology and Therapeutics, University College Cork, Clinical Investigations Building, Western Rd, Cork, Ireland.<br/>Division of Nephrology, University of California, San Francisco Medical School and San Francisco VA Medical Center, 4150 Clement Street, San Francisco, California 94121, USA.<br/>INSERM, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux F-33000, France.<br/>Universite Bordeaux, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux F-33000, France.<br/>Vanderbilt University School of Medicine, 2215-B Garland Avenue 1224-MRB4 (Light Hall)Nashville, Tennessee 37232, USA.<br/>University Heart Center Hamburg, Clinic for general and interventional cardiology, Martinistrasse 52, Hamburg 20246, Germany.<br/>German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Lubeck/Kiel, Martinistrasse 52, Hamburg 20246, Germany.<br/>Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Via Olgettina 58, Milano 20132, Italy.<br/>INSERM U1078, Etablissement Francais du Sang, 46 rue Felix Le Dantec, CS 51819, Brest Cedex 2 29218, France.<br/>Institute of Molecular Genetics-CNR, Via Abbiategrasso 207, Pavia 27100, Italy.<br/>The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.<br/>Department of Health Sciences, University of Milano, Via Antonio di Rudini 8, Milano 20142, Italy.<br/>Max Planck Institute of Psychiatry, Kraepelinstrasse 2-10, Munich 80804, Germany.<br/>Cardiovascular Health Research Unit, Departments of Epidemiology and Medicine, University of Washington, 1730 Minor Ave, Suite 1360, Seattle, Washington 98101, USA.<br/>Division of Psychiatric Genomics, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.<br/>Institute of Genetic Epidemiology, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany.<br/>Research Unit of Molecular Epidemiology, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany.<br/>Institute of Epidemiology II, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, 85764 Neuherberg, Germany.<br/>German Center for Diabetes Research (DZD), Ingolstaedter Landstrasse 1, Neuherberg 85764, Germany.<br/>Westmead Millennium Institute, Centre for Vision Research, University of Sydney, C24 Westmead Hospital, New South Wales 2145, Australia.<br/>Division of Biomedical Statistics and Informatics, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA.<br/>Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, HMRI Building1, Kookaburra Circuit, New Lambton New South Wales 2305, Australia.<br/>Clinical Research Design, Information Technology and Statistical Support, Hunter Medical Research Institute, Newcastle, 1 Kookaburra Circuit, New Lambton Heights, New South Wales 2305, Australia.<br/>Institute of Population Genetics-CNR, Traversa La Crucca 3, 07040 Reg. Baldinca, Li Punti, Sassari, Italy.<br/>Department of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, Building 2, Boston, Massachusetts 02115, USA.<br/>Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Hanzeplein 1, Groningen 9713 GZ, The Netherlands.<br/>Brigham and Women's Hospital and Channing Laboratory, Harvard Medical School, 181 Longwood Avenue, Boston, Massachusetts 02115, USA.<br/>Cardiology, Department of Specialties of Internal Medicine, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, Geneva 1205, Switzerland.<br/>Swiss Tropical and Public Health Institute, PO Box 4002, Basel, Switzerland.<br/>University of Basel, Petersplatz 1, Basel 4003, Switzerland.<br/>Division of Nephrology, Department of Internal Medicine and Medical Specialties, Columbus-Gemelli University Hospital, Catholic University, Via Moscati 31, Rome 00168, Italy.<br/>Genetic Epidemiology, Queensland Institute of Medical Research, QIMR, PO Royal Brisbane Hospital, Queensland 4029, Australia.<br/>Institute of Epidemiology and Biobank popgen, Christian-Albrechts University, Niemannsweg 11, Kiel 24105, Germany.<br/>Institute of Epidemiology I, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Ingolstadter Landstrasse 1, Neuherberg 85764, Germany.<br/>Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universitat, Ingolstadter Landstrasse 1, 85764 Neuherberg, Germany.<br/>Klinikum Grosshadern, Ingolstadter Landstrasse 1, Neuherberg 85764, Germany.<br/>Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG Scotland, UK.<br/>Austrian Stroke Prevention Study, Institute of Molecular Biology and Biochemistry, Department of Neurology, Medical University Graz, Harrachgasse 21, Graz 8010, Austria.<br/>Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Ferdinand-Sauerbruch-Strasse, Greifswald 17475, Germany.<br/>German Center for Cardiovascular Research (DZHK), Partner site Greifswald, Ferdinand-Sauerbruch-Strasse, Greifswald 17475, Germany.<br/>Institute of Pharmacology, University of Greifswald, Friedrich-Loeffler-Strasse 23d, Greifswald 17487, Germany.<br/>Boston University School of Medicine, 72 East Concord Street, B-616, Boston, Massachusetts 02118, USA.<br/>Department of Cardiology, University Medical Center Groningen, University of Groningen, PO Box 30.001, Groningen 9700 RB, The Netherlands.<br/>Robertson Centre for Biostatistics, University of Glasgow, R1122B Level 11, Robertson Centre, Boyd Orr Building, Glasgow G12 8QQ, UK.<br/>Division of Primary Care Medicine, Department of Community Medicine, Primary Care and Emergency Medicine, Geneva University Hospitals, Faculty of Medicine, University of Geneva, Geneva 1211, Switzerland.<br/>Community Prevention Unit, University Institute of Social and Preventive Medicine, Lausanne University Hospital, Route de la Corniche 10, Lausanne 1010, Switzerland.<br/>Department of Epidemiology, Rollins School of Public Health, Emory University, 1518 Clifton Road, NE, Atlanta, Georgia 30322, USA.<br/>Department of Genomics of Common Disease, School of Public Health, Imperial College London, London W12 0NN, UK.<br/>Croatian Centre for Global Health, University of Split Medical School, Soltanska 2, Split 21000, Croatia.<br/>Department of Cardiology, Leiden University Medical Center, PO Box 9600, Leiden 2300 RC, The Netherlands.<br/>Interuniversity Cardiology Institute of the Netherlands (ICIN), Moreelsepark 1, Utrecht 3511 EP, The Netherlands.<br/>Einthoven Laboratory for Experimental Vascular Medicine, Albinusdreef 2, Leiden 2333 ZA, The Netherlands.<br/>Durrer Center for Cardiogenetic Research, Meibergdreef 9, Amsterdam 1105 AZ, The Netherlands.<br/>Division of Public Health Sciences, Department of Biostatistical Sciences, Wake Forest University Health Sciences, 2326 Medical Center Boulevard, Winston-Salem, North Carolina 27157-1063, USA.<br/>INSERM U744, Institut Pasteur de Lille, 1 rue du Pr, Calmette, Lille Cedex 59019, France.<br/>Department of Epidemiology, School of Public Health, University of Michigan, 1415 Washington Heights, Ann Arbor, Michigan 48109-2029, USA.<br/>Survey Research Center, Institute for Social Research, University of Michigan, 426 Thompson Street, #3456, Ann Arbor, Michigan 48104, USA.<br/>Centre for Vision Research, Westmead Millennium Institute, University of Sydney, C24 Westmead Hospital, New South Wales 2145, Australia.<br/>Wake Forest School of Medicine, Department of Internal Medicine/Geriatrics, Medical center Boulevard, Winston-Salem, North Carolina 27157, USA.<br/>Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, NRB 0330, Boston, Massachusetts 02115, USA.<br/>University of Sydney, The George Institute for Global Health, Level 10, King George V Building, 83-117 Missenden Road, Camperdown, New South Wales 2050, Australia.<br/>Department of Medicine, University of Turku, Turku University Hospital, PO Box 52, Turku 20521, Finland.<br/>Welch Center for Prevention, Epidemiology and Clinical Research, 2024 East Monument St, Suite 2-600, Baltimore, Maryland 21287, USA.<br/>Vanderbilt University School of Medicine, 448 Eskind Biomedical Library, 2209 Garland Avenue, Nashville, Tennessee 37212, USA.<br/>Department of Genetics, University of Groningen, University Medical Centre Groningen, PO Box 72, Groningen 9700 AB, The Netherlands.<br/>Division of Endocrinology, Medical University of South Carolina, 171 Ashley Avenue, Charleston, South Carolina 29425, USA.<br/>Institute of Anatomy and Cell Biology, University of Greifswald, Friedrich-Loeffler-Strasse 23c, Greifswald 17487, Germany.<br/>Center for Health Disparities, Department of Biology, East Carolina University, 1001 East 10th Street, N209 Howell Science Complex Mailstop 551, Greenville, North Carolina 27858, USA.<br/>Intramural Research Program, Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Gateway Building, 3C309, 7201 Winsconsin Avenue, Bethesda, Maryland 20892-9205, USA.<br/>Department of Clinical Chemistry, Fimlab Laboratories, University of Tampere, School of Medicine, Tampere 33520, Finland.<br/>CNRS UMR 8199, 1 Rue du Professeur Calmette, Lille 59000, France.<br/>Lille Pasteur Institute, 1 Rue du Professeur Calmette, Lille 59000, France.<br/>Lille II University, 42 Rue paul Duez, Lille 59000, France.<br/>Clinical Research Branch, National Institute on Aging, 251 Bayview Blvd, Baltimore, Maryland 21250, USA.<br/>Department of Epidemiology and Biostatistics, Erasmus University Medical Center, Dr Molewaterplein, Rotterdam 50-603015 GE, The Netherlands.<br/>Department of Forensic Molecular Biology, Erasmus University Medical Center, Dr Molewaterplein, Rotterdam 50-603015 GE, The Netherlands.<br/>Medical Clinic V, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, Mannheim 68167, Germany.<br/>Austrian Stroke Prevention Study, Department of Neurology, Division of Special Neurology, Medical University Graz, Auenbruggerplatz 22, Graz 8036, Austria.<br/>Centre for Clinical Epidemiology and Biostatistics, University of Newcastle, Hunter Medical Research Institute, John Hunter Hospital, Locked Bag 1, HRMC, New South Wales 2310, Australia.<br/>The George Institute for Global Health, Nuffield Department of Population Health, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7LF, UK.<br/>Service of Nephrology, Lausanne University Hospital, Rue du Bugnon 17, Lausanne 1005, Switzerland.<br/>Inserm UMRS 1018, CESP Team 10, Universite Paris-Sud, 16 avenue Paul Vaillant Couturier, Villejuif 94807, France.<br/>Health Disparities Research Section, Clinical Research Branch, National Institute on Aging, National Institutes of Health, NIH Biomedical Center, 251 Bayview Boulevard, Suite 100, Baltimore, Maryland 21224, USA.<br/>Center for Public Health Genomics, Department of Medicine (Cardiovascular Medicine), University of Virginia, PO Box 800717, Charlottesville, Virginia 22908, USA.<br/>Department of Clinical Physiology, Tampere University Hospital, University of Tampere, School of Medicine, Tampere 33521, Finland.<br/>University Institute of Social and Preventive Medicine, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Route de la Corniche 2, Epalinges CH-1066, Switzerland.<br/>INSERM UMR970, Paris Cardiovascular Research Center (PARCC), 56 rue Leblanc, Paris F-75015, France.<br/>Paris Descartes University, Faculty of medicine, Paris Cite Sorbonne, 12 Rue de l'ecole de Medecine, Paris F-75006, France.<br/>Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.<br/>Wellcome Trust Sanger Institute, Hinxton CB10 1HH, UK.<br/>University of Zurich, Institute of Physiology, Mechanisms of Inherited Kidney Disorders Group, Winterthurerstrasse 190, Zurich 8057, Switzerland.<br/>Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku University Hospital, Department of Clinical Physiology, PO Box 52, Turku 20521, Finland.<br/>Department Clinical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London EC1M 6BQ, UK.<br/>NIHR Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London EC1M 6BQ, UK.<br/>Harvard Medical School, 900 Commonwealth Avenue East, Boston, Massachusetts 02115, USA.<br/>University of Alabama at Birmingham, Department of Medicine, 1530 3rd Avenue, South Birmingham, Alabama 35294-0022, USA.<br/>University of Alabama at Birmingham, Department of Epidemiology, 1530 3rd Avenue, South Birmingham, Alabama 35294-0022, USA.<br/>Department of Psychiatry and EMGO+ Institute, VU University Medical Center, A.J. Ernststraat 1187, Amsterdam 1081 HL, The Netherlands.<br/>IFB AdiposityDiseases, University of Leipzig, Liebigstrasse 21, Leipzig 04103, Germany.<br/>Medical University Center Mainz, Langenbeckstrasse 1, Mainz 55131, Germany.<br/>Institute of Physiology, University of Greifswald, Greifswald 17487, Germany.<br/>Clinic for Prosthodontic Dentistry, Gerostomatology and Material Science, University of Greifswald, Rotgerberstrasse 8, Greifswald 17475, Germany.<br/>School of Biomedical Sciences and Pharmacy, University of Newcastle, Hunter Medical Research Institute, John Hunter Hospital, Locked Bag 1, HRMC, New South Wales 2310, Australia.<br/>Kidney Research Institute, University of Washington, Box 359606, 325 9th Avenue, Seattle, Washington 98104, USA.<br/>Institute for Maternal and Child Health-IRCCS "Burlo Garofolo", Via dell'Istria 65, Trieste 34137, Italy.<br/>Department of Internal Medicine, Division of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA.<br/>Clinic for Internal Medicine A, University of Greifswald, Friedrich-Loeffler-Strasse 23a, Greifswald 17475, Germany.<br/>Faculty of Pharmaceutical Sciences, University of Iceland, Saemundargata 2, Reykjavik 101, Iceland.<br/>Department of Clinical Physiology, Turku University Hospital, Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, PO Box 52, Turku 20521, Finland.<br/>Synlab Academy, Synlab Services GmbH, Oberer Eselsberg 45, Ulm 89081, Germany.<br/>Department of Internal Medicine II-Cardiology, University of Ulm Medical Centre, Albert-Einstein-Allee 23, Ulm 89081, Germany.<br/>The Mindich Child Health and Development Institute, Ichan School of Medicine at Mount Sinai, New York, New York 10029, USA.<br/>Department of Neurology, General Central Hospital, Via Lorenz Bohler 5, Bolzano 39100, Italy.<br/>Department of Neurology, University of Lubeck, Ratzeburger Allee 160, Lubeck 23538, Germany.<br/>University of Maryland Medical School, Division of Nephrology, 685 W. Baltimore Street, MSTF 314, Baltimore, Maryland 21201, USA.<br/>CRCHUM, University of Montreal, CHUM Research Center, Technopole Angus, 900 Saint-Denis, Montreal, Quebec, Canada H2X 0A9.<br/>Division of Endocrinology, Brigham and Women s Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, Massachusetts 02115, USA.
AN - 26831199
BT - Nat CommunNat CommunNat Commun
C2 - PMC4735748
C6 - Nihms733914
DP - NLM
ET - 2016/02/03
J2 - Nature communications
LA - eng
LB - AUS<br/>UK<br/>PROF<br/>FY16
N1 - Pattaro, Cristian<br/>Teumer, Alexander<br/>Gorski, Mathias<br/>Chu, Audrey Y<br/>Li, Man<br/>Mijatovic, Vladan<br/>Garnaas, Maija<br/>Tin, Adrienne<br/>Sorice, Rossella<br/>Li, Yong<br/>Taliun, Daniel<br/>Olden, Matthias<br/>Foster, Meredith<br/>Yang, Qiong<br/>Chen, Ming-Huei<br/>Pers, Tune H<br/>Johnson, Andrew D<br/>Ko, Yi-An<br/>Fuchsberger, Christian<br/>Tayo, Bamidele<br/>Nalls, Michael<br/>Feitosa, Mary F<br/>Isaacs, Aaron<br/>Dehghan, Abbas<br/>d'Adamo, Pio<br/>Adeyemo, Adebowale<br/>Dieffenbach, Aida Karina<br/>Zonderman, Alan B<br/>Nolte, Ilja M<br/>van der Most, Peter J<br/>Wright, Alan F<br/>Shuldiner, Alan R<br/>Morrison, Alanna C<br/>Hofman, Albert<br/>Smith, Albert V<br/>Dreisbach, Albert W<br/>Franke, Andre<br/>Uitterlinden, Andre G<br/>Metspalu, Andres<br/>Tonjes, Anke<br/>Lupo, Antonio<br/>Robino, Antonietta<br/>Johansson, Asa<br/>Demirkan, Ayse<br/>Kollerits, Barbara<br/>Freedman, Barry I<br/>Ponte, Belen<br/>Oostra, Ben A<br/>Paulweber, Bernhard<br/>Kramer, Bernhard K<br/>Mitchell, Braxton D<br/>Buckley, Brendan M<br/>Peralta, Carmen A<br/>Hayward, Caroline<br/>Helmer, Catherine<br/>Rotimi, Charles N<br/>Shaffer, Christian M<br/>Muller, Christian<br/>Sala, Cinzia<br/>van Duijn, Cornelia M<br/>Saint-Pierre, Aude<br/>Ackermann, Daniel<br/>Shriner, Daniel<br/>Ruggiero, Daniela<br/>Toniolo, Daniela<br/>Lu, Yingchang<br/>Cusi, Daniele<br/>Czamara, Darina<br/>Ellinghaus, David<br/>Siscovick, David S<br/>Ruderfer, Douglas<br/>Gieger, Christian<br/>Grallert, Harald<br/>Rochtchina, Elena<br/>Atkinson, Elizabeth J<br/>Holliday, Elizabeth G<br/>Boerwinkle, Eric<br/>Salvi, Erika<br/>Bottinger, Erwin P<br/>Murgia, Federico<br/>Rivadeneira, Fernando<br/>Ernst, Florian<br/>Kronenberg, Florian<br/>Hu, Frank B<br/>Navis, Gerjan J<br/>Curhan, Gary C<br/>Ehret, George B<br/>Homuth, Georg<br/>Coassin, Stefan<br/>Thun, Gian-Andri<br/>Pistis, Giorgio<br/>Gambaro, Giovanni<br/>Malerba, Giovanni<br/>Montgomery, Grant W<br/>Eiriksdottir, Gudny<br/>Jacobs, Gunnar<br/>Li, Guo<br/>Wichmann, H-Erich<br/>Campbell, Harry<br/>Schmidt, Helena<br/>Wallaschofski, Henri<br/>Volzke, Henry<br/>Brenner, Hermann<br/>Kroemer, Heyo K<br/>Kramer, Holly<br/>Lin, Honghuang<br/>Leach, I Mateo<br/>Ford, Ian<br/>Guessous, Idris<br/>Rudan, Igor<br/>Prokopenko, Inga<br/>Borecki, Ingrid<br/>Heid, Iris M<br/>Kolcic, Ivana<br/>Persico, Ivana<br/>Jukema, J Wouter<br/>Wilson, James F<br/>Felix, Janine F<br/>Divers, Jasmin<br/>Lambert, Jean-Charles<br/>Stafford, Jeanette M<br/>Gaspoz, Jean-Michel<br/>Smith, Jennifer A<br/>Faul, Jessica D<br/>Wang, Jie Jin<br/>Ding, Jingzhong<br/>Hirschhorn, Joel N<br/>Attia, John<br/>Whitfield, John B<br/>Chalmers, John<br/>Viikari, Jorma<br/>Coresh, Josef<br/>Denny, Joshua C<br/>Karjalainen, Juha<br/>Fernandes, Jyotika K<br/>Endlich, Karlhans<br/>Butterbach, Katja<br/>Keene, Keith L<br/>Lohman, Kurt<br/>Portas, Laura<br/>Launer, Lenore J<br/>Lyytikainen, Leo-Pekka<br/>Yengo, Loic<br/>Franke, Lude<br/>Ferrucci, Luigi<br/>Rose, Lynda M<br/>Kedenko, Lyudmyla<br/>Rao, Madhumathi<br/>Struchalin, Maksim<br/>Kleber, Marcus E<br/>Cavalieri, Margherita<br/>Haun, Margot<br/>Cornelis, Marilyn C<br/>Ciullo, Marina<br/>Pirastu, Mario<br/>de Andrade, Mariza<br/>McEvoy, Mark A<br/>Woodward, Mark<br/>Adam, Martin<br/>Cocca, Massimiliano<br/>Nauck, Matthias<br/>Imboden, Medea<br/>Waldenberger, Melanie<br/>Pruijm, Menno<br/>Metzger, Marie<br/>Stumvoll, Michael<br/>Evans, Michele K<br/>Sale, Michele M<br/>Kahonen, Mika<br/>Boban, Mladen<br/>Bochud, Murielle<br/>Rheinberger, Myriam<br/>Verweij, Niek<br/>Bouatia-Naji, Nabila<br/>Martin, Nicholas G<br/>Hastie, Nick<br/>Probst-Hensch, Nicole<br/>Soranzo, Nicole<br/>Devuyst, Olivier<br/>Raitakari, Olli<br/>Gottesman, Omri<br/>Franco, Oscar H<br/>Polasek, Ozren<br/>Gasparini, Paolo<br/>Munroe, Patricia B<br/>Ridker, Paul M<br/>Mitchell, Paul<br/>Muntner, Paul<br/>Meisinger, Christa<br/>Smit, Johannes H<br/>ICBP Consortium<br/>AGEN Consortium<br/>CARDIOGRAM<br/>CHARGe-Heart Failure Group<br/>ECHOGen Consortium<br/>Kovacs, Peter<br/>Wild, Philipp S<br/>Froguel, Philippe<br/>Rettig, Rainer<br/>Magi, Reedik<br/>Biffar, Reiner<br/>Schmidt, Reinhold<br/>Middelberg, Rita P S<br/>Carroll, Robert J<br/>Penninx, Brenda W<br/>Scott, Rodney J<br/>Katz, Ronit<br/>Sedaghat, Sanaz<br/>Wild, Sarah H<br/>Kardia, Sharon L R<br/>Ulivi, Sheila<br/>Hwang, Shih-Jen<br/>Enroth, Stefan<br/>Kloiber, Stefan<br/>Trompet, Stella<br/>Stengel, Benedicte<br/>Hancock, Stephen J<br/>Turner, Stephen T<br/>Rosas, Sylvia E<br/>Stracke, Sylvia<br/>Harris, Tamara B<br/>Zeller, Tanja<br/>Zemunik, Tatijana<br/>Lehtimaki, Terho<br/>Illig, Thomas<br/>Aspelund, Thor<br/>Nikopensius, Tiit<br/>Esko, Tonu<br/>Tanaka, Toshiko<br/>Gyllensten, Ulf<br/>Volker, Uwe<br/>Emilsson, Valur<br/>Vitart, Veronique<br/>Aalto, Ville<br/>Gudnason, Vilmundur<br/>Chouraki, Vincent<br/>Chen, Wei-Min<br/>Igl, Wilmar<br/>Marz, Winfried<br/>Koenig, Wolfgang<br/>Lieb, Wolfgang<br/>Loos, Ruth J F<br/>Liu, Yongmei<br/>Snieder, Harold<br/>Pramstaller, Peter P<br/>Parsa, Afshin<br/>O'Connell, Jeffrey R<br/>Susztak, Katalin<br/>Hamet, Pavel<br/>Tremblay, Johanne<br/>de Boer, Ian H<br/>Boger, Carsten A<br/>Goessling, Wolfram<br/>Chasman, Daniel I<br/>Kottgen, Anna<br/>Kao, W H Linda<br/>Fox, Caroline S<br/>HHSN268201100009C/HL/NHLBI NIH HHS/United States<br/>K12 RR023250/RR/NCRR NIH HHS/United States<br/>P30 DK072488/DK/NIDDK NIH HHS/United States<br/>R01 AG018728/AG/NIA NIH HHS/United States<br/>R01 AG033193/AG/NIA NIH HHS/United States<br/>R01 DK058845/DK/NIDDK NIH HHS/United States<br/>R01 DK066574/DK/NIDDK NIH HHS/United States<br/>R01 DK075787/DK/NIDDK NIH HHS/United States<br/>R01 DK084350/DK/NIDDK NIH HHS/United States<br/>R01 DK089256/DK/NIDDK NIH HHS/United States<br/>R01 HL087641/HL/NHLBI NIH HHS/United States<br/>R01 HL087660/HL/NHLBI NIH HHS/United States<br/>R01 HL088119/HL/NHLBI NIH HHS/United States<br/>R01 HL117078/HL/NHLBI NIH HHS/United States<br/>R01DK090311/DK/NIDDK NIH HHS/United States<br/>R24OD017870/OD/NIH HHS/United States<br/>T32 HL007024/HL/NHLBI NIH HHS/United States<br/>U01 GM074518/GM/NIGMS NIH HHS/United States<br/>U01 HG004399/HG/NHGRI NIH HHS/United States<br/>U01 HG004402/HG/NHGRI NIH HHS/United States<br/>U01 HL072515/HL/NHLBI NIH HHS/United States<br/>U01 HL084756/HL/NHLBI NIH HHS/United States<br/>Z01 HG200362-01/Intramural NIH HHS/United States<br/>Meta-Analysis<br/>Research Support, N.I.H., Extramural<br/>England<br/>Nat Commun. 2016 Jan 21;7:10023. doi: 10.1038/ncomms10023.
N2 - Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
PY - 2016
SN - 2041-1723 (Electronic)<br/>2041-1723 (Linking)
EP - 10023
ST - Nature communicationsNature communications
T2 - Nat CommunNat CommunNat Commun
TI - Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
VL - 7
Y2 - FY16
ER -