Scientific article
Open access

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

ContributorsWinkler, Thomas W.orcid; Rasheed, Humairaorcid; Teumer, Alexanderorcid; Gorski, Mathias; Rowan, Bryce X.; Stanzick, Kira J.; Thomas, Laurent F.; Tin, Adrienneorcid; Hoppmann, Anselm; Chu, Audrey Y.; Tayo, Bamidele; Thio, Chris H. L.; Cusi, Danieleorcid; Chai, Jin-Fang; Sieber, Karsten B.; Horn, Katrin; Li, Man; Scholz, Markus; Cocca, Massimilianoorcid; Wuttke, Matthias; van der Most, Peter J.orcid; Yang, Qiongorcid; Ghasemi, Sahar; Nutile, Teresaorcid; Li, Yongorcid; Pontali, Giuliaorcid; Günther, Felix; Dehghan, Abbasorcid; Correa, Adolfo; Parsa, Afshin; Feresin, Agnese; de Vries, Aiko P. J.; Zonderman, Alan B.; Smith, Albert V.orcid; Oldehinkel, Albertine J.; De Grandi, Alessandro; Rosenkranz, Alexander R.; Franke, Andreorcid; Teren, Andrej; Metspalu, Andresorcid; Hicks, Andrew A.orcid; Morris, Andrew P.; Tönjes, Anke; Morgan, Anna; Podgornaia, Anna I.; Peters, Annette; Körner, Antje; Mahajan, Anubha; Campbell, Archie; Freedman, Barry I.orcid; Spedicati, Beatriceorcid; Ponte, Belen; Schöttker, Ben; Brumpton, Benorcid; Banas, Bernhardorcid; Krämer, Bernhard K.; Jung, Bettina; Åsvold, Bjørn Olavorcid; Smith, Blair H.orcid; Ning, Boting; Penninx, Brenda W. J. H.; Vanderwerff, Brett R.; Psaty, Bruce M.orcid; Kammerer, Candace M.; Langefeld, Carl D.orcid; Hayward, Carolineorcid; Spracklen, Cassandra N.orcid; Robinson-Cohen, Cassianne; Hartman, Catharina A.; Lindgren, Cecilia M.; Wang, Chaolongorcid; Sabanayagam, Charumathiorcid; Heng, Chew-Kiatorcid; Lanzani, Chiara; Khor, Chiea-Chuenorcid; Cheng, Ching-Yuorcid; Fuchsberger, Christian; Gieger, Christianorcid; Shaffer, Christian M.; Schulz, Christina-Alexandra; Willer, Cristen J.orcid; Chasman, Daniel I.; Gudbjartsson, Daniel F.; Ruggiero, Danielaorcid; Toniolo, Daniela; Czamara, Darinaorcid; Porteous, David J.orcid; Waterworth, Dawn M.; Mascalzoni, Deborahorcid; Mook-Kanamori, Dennis O.; Reilly, Dermot F.; Daw, E. Warwick; Hofer, Edith; Boerwinkle, Eric; Salvi, Erikaorcid; Bottinger, Erwin P.; Tai, E-Shyongorcid; Catamo, Eulaliaorcid; Rizzi, Federicaorcid; Guo, Feng; Ehret, Georg Benedikt
Published inCommunications biology, vol. 5, no. 1, 580
Publication date2022-06-13
First online date2022-06-13

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 DM = 178,691, n noDM = 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.

  • Creatinine
  • Diabetes Mellitus
  • Diabetic Nephropathies / genetics
  • Genome-Wide Association Study
  • Glomerular Filtration Rate / genetics
  • Humans
  • Kidney
Citation (ISO format)
WINKLER, Thomas W. et al. Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals. In: Communications biology, 2022, vol. 5, n° 1, p. 580. doi: 10.1038/s42003-022-03448-z
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Article (Published version)
ISSN of the journal2399-3642

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