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Genome-wide association study of kidney function decline in individuals of European descent.
Gorski, Mathias; Tin, Adrienne; Garnaas, Maija; McMahon, Gearoid M; Chu, Audrey Y; Tayo, Bamidele O; Pattaro, Cristian; Teumer, Alexander; Chasman, Daniel I; Chalmers, John; Hamet, Pavel; Tremblay, Johanne; Woodward, Marc; Aspelund, Thor; Eiriksdottir, Gudny; Gudnason, Vilmundur; Harris, Tamara B; Launer, Lenore J; Smith, Albert V; Mitchell, Braxton D; O'Connell, Jeffrey R; Shuldiner, Alan R; Coresh, Josef; Li, Man; Freudenberger, Paul; Hofer, Edith; Schmidt, Helena; Schmidt, Reinhold; Holliday, Elizabeth G; Mitchell, Paul; Wang, Jie Jin; de Boer, Ian H; Li, Guo; Siscovick, David S; Kutalik, Zoltan; Corre, Tanguy; Vollenweider, Peter; Waeber, Gérard; Gupta, Jayanta; Kanetsky, Peter A; Hwang, Shih-Jen; Olden, Matthias; Yang, Qiong; de Andrade, Mariza; Atkinson, Elizabeth J; Kardia, Sharon L R; Turner, Stephen T; Stafford, Jeanette M; Ding, Jingzhong; Liu, Yongmei.
Afiliação
  • Gorski M; 1] Department of Genetic Epidemiology, Institute of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany [2] Department of Nephrology, University Hospital Regensburg, Regensburg, Germany.
  • Tin A; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
  • Garnaas M; Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  • McMahon GM; 1] Division of Nephrology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA [2] NHLBI's Framingham Heart Study, National Heart, Lung and Blood Institute, Framingham, Massachusetts, USA.
  • Chu AY; Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
  • Tayo BO; Department of Public Health Services, Loyola Medical Center, Loyola University Chicago, Maywood, Illinois, USA.
  • Pattaro C; Center for Biomedicine, European Academy of Bozen/Bolzano (EURAC), affiliated to the University of Lübeck, Bolzano, Italy.
  • Teumer A; Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany.
  • Chasman DI; Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
  • Chalmers J; George Institute for Global Health, University of Sydney, Sydney, New South Wales, Australia.
  • Hamet P; Centre de recherche du Centre hospitalier de l'Université de Montréal, University of Montreal, Montreal, Quebec, Canada.
  • Tremblay J; CHUM Research Center- Technopôle Angus, Montreal, Québec, Canada.
  • Woodward M; George Institute for Global Health, University of Sydney, Sydney, New South Wales, Australia.
  • Aspelund T; 1] Icelandic Heart Association, Research Institute, Kopavogur, Iceland [2] University of Iceland, Reykjavik, Iceland.
  • Eiriksdottir G; Icelandic Heart Association, Research Institute, Kopavogur, Iceland.
  • Gudnason V; 1] Icelandic Heart Association, Research Institute, Kopavogur, Iceland [2] University of Iceland, Reykjavik, Iceland.
  • Harris TB; Intramural Research Program, Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, Maryland, USA.
  • Launer LJ; Intramural Research Program, Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, Maryland, USA.
  • Smith AV; 1] Icelandic Heart Association, Research Institute, Kopavogur, Iceland [2] University of Iceland, Reykjavik, Iceland.
  • Mitchell BD; 1] Department of Medicine and Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA [2] Geriatric Research and Education Clinical Center, Veterans Administration Medical Center, University of Maryland School of Medicine, Baltimore, Marylan
  • O'Connell JR; Department of Medicine and Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
  • Shuldiner AR; 1] Department of Medicine and Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA [2] Geriatric Research and Education Clinical Center, Veterans Administration Medical Center, University of Maryland School of Medicine, Baltimore, Marylan
  • Coresh J; 1] Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA [2] Welch Center for Prevention, Epidemiology and Clinical Research, Baltimore, Maryland, USA.
  • Li M; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
  • Freudenberger P; Institute of Molecular Biology and Biochemistry, Medical University Graz, Graz, Austria.
  • Hofer E; Department of Neurology, Institute for Medical Informatics, Statistics and Documentation, Medical University Graz, Graz, Austria.
  • Schmidt H; Institute of Molecular Biology and Biochemistry, Medical University Graz, Graz, Austria.
  • Schmidt R; Department of Neurology, Medical University Graz, Graz, Austria.
  • Holliday EG; Centre for Clinical Epidemiology and Biostatistics, University of Newcastle, CReDITSS, HMRI, Callaghan, New South Wales, Australia.
  • Mitchell P; Centre for Vision Research, Westmead Millennium Institute, University of Sydney, Westmead Hospital, Sydney, New South Wales, Australia.
  • Wang JJ; Centre for Vision Research, Westmead Millennium Institute, University of Sydney, Westmead Hospital, Sydney, New South Wales, Australia.
  • de Boer IH; University of Washington, Seattle, Washington, USA.
  • Li G; Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, USA.
  • Siscovick DS; 1] Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, USA [2] New York Academy of Medicine, New York, New York, USA.
  • Kutalik Z; 1] Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland [2] Department of Medical Genetics, Swiss Institute of Bioinformatics, Lausanne, Switzerland.
  • Corre T; Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland.
  • Vollenweider P; Internal Medicine Department, Lausanne University Hospital, Lausanne, Switzerland.
  • Waeber G; Internal Medicine Department, Lausanne University Hospital, Lausanne, Switzerland.
  • Gupta J; Perelman School of Medicine at the University of Pennsylvania, Center for Clinical Epidemiology and Biostatistics.
  • Kanetsky PA; Perelman School of Medicine at the University of Pennsylvania, Center for Clinical Epidemiology and Biostatistics.
  • Hwang SJ; NHLBI's Framingham Heart Study, National Heart, Lung and Blood Institute, Framingham, Massachusetts, USA.
  • Olden M; 1] Department of Genetic Epidemiology, Institute of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany [2] NHLBI's Framingham Heart Study, National Heart, Lung and Blood Institute, Framingham, Massachusetts, USA.
  • Yang Q; 1] NHLBI's Framingham Heart Study, National Heart, Lung and Blood Institute, Framingham, Massachusetts, USA [2] Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.
  • de Andrade M; Mayo Clinic, Rochester, Minnesota, USA.
  • Atkinson EJ; Mayo Clinic, Rochester, Minnesota, USA.
  • Kardia SL; University of Michigan, Ann Arbor, Michigan, USA.
  • Turner ST; Mayo Clinic, Rochester, Minnesota, USA.
  • Stafford JM; Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
  • Ding J; Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
  • Liu Y; Department of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
Kidney Int ; 87(5): 1017-29, 2015 May.
Article em En | MEDLINE | ID: mdl-25493955
Genome-wide association studies (GWASs) have identified multiple loci associated with cross-sectional eGFR, but a systematic genetic analysis of kidney function decline over time is missing. Here we conducted a GWAS meta-analysis among 63,558 participants of European descent, initially from 16 cohorts with serial kidney function measurements within the CKDGen Consortium, followed by independent replication among additional participants from 13 cohorts. In stage 1 GWAS meta-analysis, single-nucleotide polymorphisms (SNPs) at MEOX2, GALNT11, IL1RAP, NPPA, HPCAL1, and CDH23 showed the strongest associations for at least one trait, in addition to the known UMOD locus, which showed genome-wide significance with an annual change in eGFR. In stage 2 meta-analysis, the significant association at UMOD was replicated. Associations at GALNT11 with Rapid Decline (annual eGFR decline of 3 ml/min per 1.73 m(2) or more), and CDH23 with eGFR change among those with CKD showed significant suggestive evidence of replication. Combined stage 1 and 2 meta-analyses showed significance for UMOD, GALNT11, and CDH23. Morpholino knockdowns of galnt11 and cdh23 in zebrafish embryos each had signs of severe edema 72 h after gentamicin treatment compared with controls, but no gross morphological renal abnormalities before gentamicin administration. Thus, our results suggest a role in the deterioration of kidney function for the loci GALNT11 and CDH23, and show that the UMOD locus is significantly associated with kidney function decline.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Caderinas / N-Acetilgalactosaminiltransferases / Insuficiência Renal / Uromodulina Idioma: En Ano de publicação: 2015 Tipo de documento: Article
Texto completo
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PubMed Links
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Caderinas / N-Acetilgalactosaminiltransferases / Insuficiência Renal / Uromodulina Idioma: En Ano de publicação: 2015 Tipo de documento: Article