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Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals.
Winkler, Thomas W; Rasheed, Humaira; Teumer, Alexander; Gorski, Mathias; Rowan, Bryce X; Stanzick, Kira J; Thomas, Laurent F; Tin, Adrienne; Hoppmann, Anselm; Chu, Audrey Y; Tayo, Bamidele; Thio, Chris H L; Cusi, Daniele; Chai, Jin-Fang; Sieber, Karsten B; Horn, Katrin; Li, Man; Scholz, Markus; Cocca, Massimiliano; Wuttke, Matthias; van der Most, Peter J; Yang, Qiong; Ghasemi, Sahar; Nutile, Teresa; Li, Yong; Pontali, Giulia; Günther, Felix; Dehghan, Abbas; Correa, Adolfo; Parsa, Afshin; Feresin, Agnese; de Vries, Aiko P J; Zonderman, Alan B; Smith, Albert V; Oldehinkel, Albertine J; De Grandi, Alessandro; Rosenkranz, Alexander R; Franke, Andre; Teren, Andrej; Metspalu, Andres; Hicks, Andrew A; Morris, Andrew P; Tönjes, Anke; Morgan, Anna; Podgornaia, Anna I; Peters, Annette; Körner, Antje; Mahajan, Anubha; Campbell, Archie; Freedman, Barry I.
Affiliation
  • Winkler TW; Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany. thomas.winkler@ukr.de.
  • Rasheed H; K. G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
  • Teumer A; MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
  • Gorski M; Division of Medicine and Laboratory Sciences, University of Oslo, Oslo, Norway.
  • Rowan BX; Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
  • Stanzick KJ; DZHK (German Center for Cardiovascular Research), partner site Greifswald, Greifswald, Germany.
  • Thomas LF; Department of Population Medicine and Lifestyle Diseases Prevention, Medical University of Bialystok, Bialystok, Poland.
  • Tin A; Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany.
  • Hoppmann A; Department of Nephrology, University Hospital Regensburg, Regensburg, Germany.
  • Chu AY; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Tayo B; Department of Veteran's Affairs, Tennessee Valley Healthcare System (626)/Vanderbilt University, Nashville, TN, USA.
  • Thio CHL; Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany.
  • Cusi D; K. G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
  • Chai JF; Department of Clinical and Molecular Medicine, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
  • Sieber KB; BioCore-Bioinformatics Core Facility, Norwegian University of Science and Technology, Trondheim, Norway.
  • Horn K; Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
  • Li M; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
  • Scholz M; Institute of Genetic Epidemiology, Department of Data Driven Medicine, Faculty of Medicine and Medical Center-University of Freiburg, Freiburg, Germany.
  • Cocca M; Genetics, Merck & Co., Inc, Kenilworth, NJ, USA.
  • Wuttke M; Department of Public Health Sciences, Loyola University Chicago, Maywood, IL, USA.
  • van der Most PJ; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • Yang Q; Institute of Biomedical Technologies, National Research Council of Italy, Milan, Italy.
  • Ghasemi S; Bio4Dreams-Business Nursery for Life Sciences, Milan, Italy.
  • Nutile T; Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.
  • Li Y; Target Sciences-Genetics, GlaxoSmithKline, Collegeville, PA, USA.
  • Pontali G; Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
  • Günther F; LIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany.
  • Dehghan A; Division of Nephrology and Hypertension, Department of Medicine, University of Utah, Salt Lake City, UT, USA.
  • Correa A; Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
  • Parsa A; LIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany.
  • Feresin A; Institute for Maternal and Child Health, IRCCS 'Burlo Garofolo', Trieste, Italy.
  • de Vries APJ; Institute of Genetic Epidemiology, Department of Data Driven Medicine, Faculty of Medicine and Medical Center-University of Freiburg, Freiburg, Germany.
  • Zonderman AB; Renal Division, Department of Medicine IV, Faculty of Medicine and Medical Center-University of Freiburg, Freiburg, Germany.
  • Smith AV; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • Oldehinkel AJ; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
  • De Grandi A; Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
  • Rosenkranz AR; DZHK (German Center for Cardiovascular Research), partner site Greifswald, Greifswald, Germany.
  • Franke A; Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
  • Teren A; Institute of Genetics and Biophysics 'Adriano Buzzati-Traverso'-CNR, Naples, Italy.
  • Metspalu A; Institute of Genetic Epidemiology, Department of Data Driven Medicine, Faculty of Medicine and Medical Center-University of Freiburg, Freiburg, Germany.
  • Hicks AA; Eurac Research, Institute for Biomedicine (affiliated with the University of Lübeck), Bolzano, Italy.
  • Morris AP; University of Trento, Department of Cellular, Computational and Integrative Biology-CIBIO, Trento, Italy.
  • Tönjes A; Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany.
  • Morgan A; Statistical Consulting Unit StaBLab, Department of Statistics, LMU Munich, Munich, Germany.
  • Podgornaia AI; MRC Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Medicine, Imperial College London, London, UK.
  • Peters A; Dementia Research Institute, Imperial College London, London, UK.
  • Körner A; Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
  • Mahajan A; Division of Kidney, Urologic and Hematologic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Campbell A; University of Maryland School of Medicine, Baltimore, MD, USA.
  • Freedman BI; Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy.
Commun Biol ; 5(1): 580, 2022 06 13.
Article in En | MEDLINE | ID: mdl-35697829
ABSTRACT
Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (nDM = 178,691, nnoDM = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Diabetes Mellitus / Diabetic Nephropathies Type of study: Prognostic_studies / Risk_factors_studies / Systematic_reviews Limits: Humans Language: En Journal: Commun Biol Year: 2022 Document type: Article Affiliation country: Germany
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Diabetes Mellitus / Diabetic Nephropathies Type of study: Prognostic_studies / Risk_factors_studies / Systematic_reviews Limits: Humans Language: En Journal: Commun Biol Year: 2022 Document type: Article Affiliation country: Germany