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Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.
Pattaro, Cristian; Teumer, Alexander; Gorski, Mathias; Chu, Audrey Y; Li, Man; Mijatovic, Vladan; Garnaas, Maija; Tin, Adrienne; Sorice, Rossella; Li, Yong; Taliun, Daniel; Olden, Matthias; Foster, Meredith; Yang, Qiong; Chen, Ming-Huei; Pers, Tune H; Johnson, Andrew D; Ko, Yi-An; Fuchsberger, Christian; Tayo, Bamidele; Nalls, Michael; Feitosa, Mary F; Isaacs, Aaron; Dehghan, Abbas; d'Adamo, Pio; Adeyemo, Adebowale; Dieffenbach, Aida Karina; Zonderman, Alan B; Nolte, Ilja M; van der Most, Peter J; Wright, Alan F; Shuldiner, Alan R; Morrison, Alanna C; Hofman, Albert; Smith, Albert V; Dreisbach, Albert W; Franke, Andre; Uitterlinden, Andre G; Metspalu, Andres; Tonjes, Anke; Lupo, Antonio; Robino, Antonietta; Johansson, Åsa; Demirkan, Ayse; Kollerits, Barbara; Freedman, Barry I; Ponte, Belen; Oostra, Ben A; Paulweber, Bernhard; Krämer, Bernhard K.
Afiliação
  • Pattaro C; Center for Biomedicine, European Academy of Bozen/Bolzano (EURAC), affiliated to the University of Lübeck, Via Galvani 31, Bolzano 39100, Italy.
  • Teumer A; Interfaculty Institute for Genetics and Functional Genomics, Ernst-Moritz-Arndt-University Greifswald, Friedrich-Loeffler-Straße 15a, Greifswald 17487, Germany.
  • Gorski M; Institute for Community Medicine, University of Greifswald, Walther-Rathenau-Strasse 48, Greifswald 17487, Germany.
  • Chu AY; Department of Genetic Epidemiology, Institute of Epidemiology and Preventive Medicine, University of Regensburg, Franz-Josef-Strauß-Allee 11, Regensburg 93053, Germany.
  • Li M; Department of Nephrology, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, Regensburg 93053, Germany.
  • Mijatovic V; Preventive Medicine, Brigham and Women's Hospital, 900 Commonwealth Avenue East, Boston, Massachusetts 02215, USA.
  • Garnaas M; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, Maryland 21205, USA.
  • Tin A; Department of Life and Reproduction Sciences, University of Verona, Strada Le Grazie 8, Verona 37134, Italy.
  • Sorice R; 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.
  • Li Y; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, Maryland 21205, USA.
  • Taliun D; Institute of Genetics and Biophysics "Adriano Buzzati-Traverso"-CNR, Via P. Castellino 111, Napoli 80131, Italy.
  • Olden M; Department of Internal Medicine IV, University Hospital Freiburg, Berliner Allee 29, Freiburg 79110, Germany.
  • Foster M; Center for Biomedicine, European Academy of Bozen/Bolzano (EURAC), affiliated to the University of Lübeck, Via Galvani 31, Bolzano 39100, Italy.
  • Yang Q; Department of Genetic Epidemiology, Institute of Epidemiology and Preventive Medicine, University of Regensburg, Franz-Josef-Strauß-Allee 11, Regensburg 93053, Germany.
  • Chen MH; Department of Nephrology, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, Regensburg 93053, Germany.
  • Pers TH; Division of Nephrology/Tufts Evidence Practice Center, Tufts University School of Medicine, Tufts Medical Center, Boston, Massachusetts 02111, USA.
  • Johnson AD; Department of Biostatistics, Boston University School of Public Health, 715 Albany Street, Boston, Massachusetts 02118, USA.
  • Ko YA; Department of Biostatistics, Boston University School of Public Health, 715 Albany Street, Boston, Massachusetts 02118, USA.
  • Fuchsberger C; Department of Neurology, Boston University School of Medicine, 72 East Concord ST B603, Boston, Massachusetts 02118, USA.
  • Tayo B; Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children's Hospital, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
  • Nalls M; Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 2142, USA.
  • Feitosa MF; NHLBI's Framingham Heart Study and the Center for Population Studies, 73 Mt Wayte Avenue, Suite 2, Framingham, Massachusetts 01702, USA.
  • Isaacs A; Renal Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, 415 Curie Boulevard, 405B Clinical Research Building, Philadelphia, Pennsylvania 19104-4539, USA.
  • Dehghan A; Center for Biomedicine, European Academy of Bozen/Bolzano (EURAC), affiliated to the University of Lübeck, Via Galvani 31, Bolzano 39100, Italy.
  • d'Adamo P; Department of Public Health Sciences, Loyola Medical Center, 2160 S First Avenue, Maywood, Illinois 60153, USA.
  • Adeyemo A; Laboratory of Neurogenetics, Building 35-Porter Building, 1A1015, National Institute on Aging/NIH, Bethesda, Maryland 20892, USA.
  • Dieffenbach AK; Division of Statistical Genomics, Washington University School of Medicine, 4444 Forest Park Boulevard, Box 8506, St Louis, Missouri 63108, USA.
  • Zonderman AB; Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Dr Molewaterplein 50, PO Box 2040, Rotterdam 3000 CA, The Netherlands.
  • Nolte IM; Centre for Medical Systems Biology Leiden, Dr Molewaterplein 50, PO Box 2040, Rotterdam 3000 CA, The Netherlands.
  • van der Most PJ; Department of Epidemiology, Erasmus University Medical Center, PO Box 2040, Rotterdam 3000 CA, The Netherlands.
  • Wright AF; Institute for Maternal and Child Health-IRCCS "Burlo Garofolo" and University of Trieste, via dell'Istria 65/1, Trieste 34137, Italy.
  • Shuldiner AR; 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.
  • Morrison AC; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, Heidelberg 69120, Germany.
  • Hofman A; German Cancer Consortium (DKTK), Im Neuenheimer Feld 581, Heidelberg 69120, Germany.
  • Smith AV; 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.
  • Dreisbach AW; Unit of Genetic Epidemiology and Bioinformatics, Department of Epidemiology, University Medical Center Groningen, PO Box 30001, Groningen 9700 RB, The Netherlands.
  • Franke A; Unit of Genetic Epidemiology and Bioinformatics, Department of Epidemiology, University Medical Center Groningen, PO Box 30001, Groningen 9700 RB, The Netherlands.
  • Uitterlinden AG; MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road, Edinburgh EH4 2XU, UK.
  • Metspalu A; Department of Medicine, University of Maryland School of Medicine, 685 West Baltimore Street, Baltimore, Maryland 21201, USA.
  • Tonjes A; Geriatric Research and Education Clinical Center, Veterans Administration Medical Center, 10 North Greene Street, Baltimore, Maryland 21201, USA.
  • Lupo A; Human Genetics Center, University of Texas Health Science Center at Houston, 1200 Pressler St Suite 453E, Houston, Texas 77030, USA.
  • Robino A; Department of Epidemiology, Erasmus University Medical Center, PO Box 2040, Rotterdam 3000 CA, The Netherlands.
  • Johansson Å; Icelandic Heart Association, Research Institute, Holtasmari 1, Kopavogur 201, Iceland.
  • Demirkan A; University of Iceland, Sæmundargötu 2, Reykjavik 101, Iceland.
  • Kollerits B; Division of Nephrology, University of Mississippi, 2500 North State Street, Jackson, Mississippi 39216, USA.
  • Freedman BI; Institute of Clinical Molecular Biology, Christian-Albrechts University of Kiel, Schittenhelmstraße 12, Kiel 24105, Germany.
  • Ponte B; Department of Internal Medicine, Erasmus University Medical Center, PO Box 1738, Rotterdam 3000 DR, The Netherlands.
  • Oostra BA; Estonian Genome Center of University of Tartu (EGCUT), Riia 23B, Tartu 51010, Estonia.
  • Paulweber B; Institute of Molecular and Cell Biology, University of Tartu and Estonian Biocenter, Riia 23, Tartu 51010, Estonia.
  • Krämer BK; Department of Medicine, University of Leipzig, Liebigstraße 18, Leipzig 04103, Germany.
Nat Commun ; 7: 10023, 2016 Jan 21.
Article em En | MEDLINE | ID: mdl-26831199
ABSTRACT
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Predisposição Genética para Doença / Insuficiência Renal Crônica Tipo de estudo: Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Humans Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Itália
Texto completo
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PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Predisposição Genética para Doença / Insuficiência Renal Crônica Tipo de estudo: Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Humans Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Itália