Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals

Thomas W. Winkler, Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany. thomas.winkler@ukr.de.
Humaira Rasheed, 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.
Alexander Teumer, Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
Mathias Gorski, Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany.
Bryce X. Rowan, Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.
Kira J. Stanzick, Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany.
Laurent F. Thomas, 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.
Adrienne Tin, Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
Anselm Hoppmann, Institute of Genetic Epidemiology, Department of Data Driven Medicine, Faculty of Medicine and Medical Center-University of Freiburg, Freiburg, Germany.
Audrey Y. Chu, Genetics, Merck & Co., Inc, Kenilworth, NJ, USA.
Bamidele Tayo, Department of Public Health Sciences, Loyola University Chicago, Maywood, IL, USA.
Chris H. Thio, Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Daniele Cusi, Institute of Biomedical Technologies, National Research Council of Italy, Milan, Italy.
Jin-Fang Chai, Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.
Karsten B. Sieber, Target Sciences-Genetics, GlaxoSmithKline, Collegeville, PA, USA.
Katrin Horn, Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
Man Li, Division of Nephrology and Hypertension, Department of Medicine, University of Utah, Salt Lake City, UT, USA.
Markus Scholz, Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
Massimiliano Cocca, Institute for Maternal and Child Health, IRCCS 'Burlo Garofolo', Trieste, Italy.
Matthias Wuttke, Institute of Genetic Epidemiology, Department of Data Driven Medicine, Faculty of Medicine and Medical Center-University of Freiburg, Freiburg, Germany.
Peter J. van der Most, Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Qiong Yang, Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Sahar Ghasemi, Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
Teresa Nutile, Institute of Genetics and Biophysics 'Adriano Buzzati-Traverso'-CNR, Naples, Italy.
Yong Li, Institute of Genetic Epidemiology, Department of Data Driven Medicine, Faculty of Medicine and Medical Center-University of Freiburg, Freiburg, Germany.
Giulia Pontali, Eurac Research, Institute for Biomedicine (affiliated with the University of Lübeck), Bolzano, Italy.
Felix Günther, Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany.
Abbas Dehghan, MRC Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Medicine, Imperial College London, London, UK.
Adolfo Correa, Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
Afshin Parsa, Division of Kidney, Urologic and Hematologic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Agnese Feresin, Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy.
Aiko P. de Vries, Section of Nephrology, Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands.

Document Type

Journal Article

Publication Date

6-13-2022

Journal

Communications biology

Volume

5

Issue

1

DOI

10.1038/s42003-022-03448-z

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 (n = 178,691, n = 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.

Department

Exercise and Nutrition Sciences

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