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

Lifelines cohort study; DiscovEHR/MyCode study; VA Million Veteran Program; 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.; Kuusisto, Johanna; Nikus, Kjell; Lyytikäinen, Leo Pekka; Kähönen, Mika; Hutri-Kähönen, Nina; Mononen, Nina; Mishra, Pashupati P.; Kovacs, Peter; Lehtimäki, Terho (2022-06)
 
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Lifelines cohort study
DiscovEHR/MyCode study
VA Million Veteran Program
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.
Kuusisto, Johanna
Nikus, Kjell
Lyytikäinen, Leo Pekka
Kähönen, Mika
Hutri-Kähönen, Nina
Mononen, Nina
Mishra, Pashupati P.
Kovacs, Peter
Lehtimäki, Terho
06 / 2022


580
doi:10.1038/s42003-022-03448-z
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https://urn.fi/URN:NBN:fi:tuni-202208206564

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Peer reviewed
Tiivistelmä
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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