TY - JOUR
T1 - Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals
AU - Lifelines Cohort Study
AU - DiscovEHR/MyCode study
AU - VA Million Veteran Program
AU - Winkler, Thomas W.
AU - Rasheed, Humaira
AU - Teumer, Alexander
AU - Gorski, Mathias
AU - Rowan, Bryce X.
AU - Stanzick, Kira J.
AU - Thomas, Laurent F.
AU - Tin, Adrienne
AU - Hoppmann, Anselm
AU - Chu, Audrey Y.
AU - Tayo, Bamidele
AU - Thio, Chris H.L.
AU - Cusi, Daniele
AU - Chai, Jin Fang
AU - Sieber, Karsten B.
AU - Horn, Katrin
AU - Li, Man
AU - Scholz, Markus
AU - Cocca, Massimiliano
AU - Wuttke, Matthias
AU - van der Most, Peter J.
AU - Yang, Qiong
AU - Ghasemi, Sahar
AU - Nutile, Teresa
AU - Li, Yong
AU - Pontali, Giulia
AU - Günther, Felix
AU - Dehghan, Abbas
AU - Correa, Adolfo
AU - Parsa, Afshin
AU - Feresin, Agnese
AU - de Vries, Aiko P.J.
AU - Zonderman, Alan B.
AU - Smith, Albert V.
AU - Oldehinkel, Albertine J.
AU - De Grandi, Alessandro
AU - Rosenkranz, Alexander R.
AU - Franke, Andre
AU - Teren, Andrej
AU - Metspalu, Andres
AU - Hicks, Andrew A.
AU - Morris, Andrew P.
AU - Tönjes, Anke
AU - Morgan, Anna
AU - Podgornaia, Anna I.
AU - Peters, Annette
AU - Körner, Antje
AU - Mahajan, Anubha
AU - Campbell, Archie
AU - Meitinger, Thomas
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12/1
Y1 - 2022/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85131867525&partnerID=8YFLogxK
U2 - 10.1038/s42003-022-03448-z
DO - 10.1038/s42003-022-03448-z
M3 - Article
C2 - 35697829
AN - SCOPUS:85131867525
SN - 2399-3642
VL - 5
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 580
ER -
