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A catalog of genetic loci associated with kidney function from analyses of a million individuals.
Wuttke, Matthias; Li, Yong; Li, Man; Sieber, Karsten B; Feitosa, Mary F; Gorski, Mathias; Tin, Adrienne; Wang, Lihua; Chu, Audrey Y; Hoppmann, Anselm; Kirsten, Holger; Giri, Ayush; Chai, Jin-Fang; Sveinbjornsson, Gardar; Tayo, Bamidele O; Nutile, Teresa; Fuchsberger, Christian; Marten, Jonathan; Cocca, Massimiliano; Ghasemi, Sahar; Xu, Yizhe; Horn, Katrin; Noce, Damia; van der Most, Peter J; Sedaghat, Sanaz; Yu, Zhi; Akiyama, Masato; Afaq, Saima; Ahluwalia, Tarunveer S; Almgren, Peter; Amin, Najaf; Ärnlöv, Johan; Bakker, Stephan J L; Bansal, Nisha; Baptista, Daniela; Bergmann, Sven; Biggs, Mary L; Biino, Ginevra; Boehnke, Michael; Boerwinkle, Eric; Boissel, Mathilde; Bottinger, Erwin P; Boutin, Thibaud S; Brenner, Hermann; Brumat, Marco; Burkhardt, Ralph; Butterworth, Adam S; Campana, Eric; Campbell, Archie; Campbell, Harry.
Afiliação
  • Wuttke M; Institute of Genetic Epidemiology, Department of Biometry, Epidemiology and Medical Bioinformatics, Faculty of Medicine and Medical Center-University of Freiburg, Freiburg, Germany.
  • Li Y; Renal Division, Department of Medicine IV, Faculty of Medicine and Medical Center-University of Freiburg, Freiburg, Germany.
  • Li M; Institute of Genetic Epidemiology, Department of Biometry, Epidemiology and Medical Bioinformatics, Faculty of Medicine and Medical Center-University of Freiburg, Freiburg, Germany.
  • Sieber KB; Division of Nephrology and Hypertension, Department of Medicine, University of Utah, Salt Lake City, USA.
  • Feitosa MF; Target Sciences-Genetics, GlaxoSmithKline, Collegeville, PA, USA.
  • Gorski M; Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.
  • Tin A; Department of Nephrology, University Hospital Regensburg, Regensburg, Germany.
  • Wang L; Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany.
  • Chu AY; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
  • Hoppmann A; Welch Center for Prevention, Epidemiology and Clinical Research, Baltimore, MD, USA.
  • Kirsten H; Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.
  • Giri A; Genetics, Merck & Co., Inc, Kenilworth, NJ, USA.
  • Chai JF; Institute of Genetic Epidemiology, Department of Biometry, Epidemiology and Medical Bioinformatics, Faculty of Medicine and Medical Center-University of Freiburg, Freiburg, Germany.
  • Sveinbjornsson G; Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
  • Tayo BO; LIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany.
  • Nutile T; Division of Quantitative Sciences, Department of Obstetrics & Gynecology, Vanderbilt Genetics Institute, Vanderbilt Epidemiology Center, Institute for Medicine and Public Health, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Fuchsberger C; Biomedical Laboratory Research and Development, Tennessee Valley Healthcare System (626)/Vanderbilt University, Nashville, TN, USA.
  • Marten J; Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.
  • Cocca M; deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
  • Ghasemi S; Department of Public Health Sciences, Loyola University Chicago, Maywood, IL, USA.
  • Xu Y; Institute of Genetics and Biophysics 'Adriano Buzzati-Traverso'-CNR, Naples, Italy.
  • Horn K; Eurac Research, Institute for Biomedicine (affiliated with the University of Lübeck), Bolzano, Italy.
  • Noce D; Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
  • van der Most PJ; Institute for Maternal and Child Health, IRCCS 'Burlo Garofolo', Trieste, Italy.
  • Sedaghat S; Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
  • Yu Z; DZHK (German Center for Cardiovascular Research), partner site Greifswald, Greifswald, Germany.
  • Akiyama M; Division of Nephrology and Hypertension, Department of Medicine, University of Utah, Salt Lake City, USA.
  • Afaq S; Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
  • Ahluwalia TS; LIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany.
  • Almgren P; Eurac Research, Institute for Biomedicine (affiliated with the University of Lübeck), Bolzano, Italy.
  • Amin N; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
  • Ärnlöv J; Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
  • Bakker SJL; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
  • Bansal N; Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
  • Baptista D; Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Japan.
  • Bergmann S; Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
  • Biggs ML; Department of Epidemiology and Biostatistics, Faculty of Medicine, School of Public Health, Imperial College London, London, UK.
  • Biino G; Institute of Public Health & Social Sciences, Khyber Medical University, Peshawar, Pakistan.
  • Boehnke M; Steno Diabetes Center Copenhagen, Gentofte, Denmark.
  • Boerwinkle E; Diabetes and Cardiovascular Disease-Genetic Epidemiology, Department of Clincial Sciences in Malmö, Lund University, Malmö, Sweden.
  • Boissel M; Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
  • Bottinger EP; Division of Family Medicine and Primary Care, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
  • Boutin TS; School of Health and Social Studies, Dalarna University, Stockholm, Sweden.
  • Brenner H; Division of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
  • Brumat M; Division of Nephrology, University of Washington, Seattle, WA, USA.
  • Burkhardt R; Kidney Research Institute, University of Washington, Seattle, WA, USA.
  • Butterworth AS; Cardiology, Geneva University Hospitals, Geneva, Switzerland.
  • Campana E; Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
  • Campbell A; Swiss Institute of Bioinformatics, Lausanne, Switzerland.
  • Campbell H; Department of Integrative Biomedical Sciences, University of Cape Town, Cape Town, South Africa.
Nat Genet ; 51(6): 957-972, 2019 06.
Article em En | MEDLINE | ID: mdl-31152163
ABSTRACT
Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Característica Quantitativa Herdável / Predisposição Genética para Doença / Locos de Características Quantitativas / Insuficiência Renal Crônica / Estudos de Associação Genética Tipo de estudo: Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Característica Quantitativa Herdável / Predisposição Genética para Doença / Locos de Características Quantitativas / Insuficiência Renal Crônica / Estudos de Associação Genética Tipo de estudo: Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article