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

Thomas W. Winkler; Humaira Rasheed; The LifeLines Cohort Study; DiscovEHR and MyCode Community Health Initiative; VA Million Veteran Program; Alexander Teumer; Mathias Gorski; Bryce X. Rowan; Kira J. Stanzick; Laurent F. Thomas; Adrienne Tin; Anselm Hoppmann; Audrey Y. Chu; Bamidele Tayo; Chris H.L. Thio; Daniele Cusi; Jin Fang Chai; Karsten B. Sieber; Katrin Horn; Man Li; Markus Scholz; Massimiliano Cocca; Matthias Wuttke; Peter J. van der Most; Qiong Yang; Sahar Ghasemi; Teresa Nutile; Yong Li; Giulia Pontali; Felix Günther; Abbas Dehghan; Adolfo Correa; Afshin Parsa; Agnese Feresin; Aiko P.J. de Vries; Alan B. Zonderman; Albert V. Smith; Albertine J. Oldehinkel; Alessandro De Grandi; Alexander R. Rosenkranz; Fernando Rivadeneira; Helena Schmidt; Janine F. Felix; M. Arfan Ikram; Maryam Kavousi; Mohsen Ghanbari; Niek Verweij; Raymond Noordam; Sanaz Sedaghat; Suzanne Vogelezang; Tien Yin Wong; Vincent W.V. Jaddoe; Ya Xing Wang

doi:10.1038/s42003-022-03448-z

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

Thomas W. Winkler^*
, Humaira Rasheed
, The LifeLines Cohort Study
, DiscovEHR and MyCode Community Health Initiative
, VA Million Veteran Program
, Alexander Teumer
, Mathias Gorski
, Bryce X. Rowan
, Kira J. Stanzick
, Laurent F. Thomas
, Adrienne Tin
, Anselm Hoppmann
, Audrey Y. Chu
, Bamidele Tayo
, Chris H.L. Thio
, Daniele Cusi
, Jin Fang Chai
, Karsten B. Sieber
, Katrin Horn
, Man Li

Markus Scholz, Massimiliano Cocca, Matthias Wuttke, Peter J. van der Most, Qiong Yang, Sahar Ghasemi, Teresa Nutile, Yong Li, Giulia Pontali, Felix Günther, Abbas Dehghan, Adolfo Correa, Afshin Parsa, Agnese Feresin, Aiko P.J. de Vries, Alan B. Zonderman, Albert V. Smith, Albertine J. Oldehinkel, Alessandro De Grandi, Alexander R. Rosenkranz, Fernando Rivadeneira, Helena Schmidt, Janine F. Felix, M. Arfan Ikram, Maryam Kavousi, Mohsen Ghanbari, Niek Verweij, Raymond Noordam, Sanaz Sedaghat, Suzanne Vogelezang, Tien Yin Wong, Vincent W.V. Jaddoe, Ya Xing Wang

^*Corresponding author for this work

University of Regensburg
Norwegian University of Science and Technology
Bristol Medical School
University of Oslo
Vanderbilt University School of Medicine
Vanderbilt University
University of Mississippi Medical Center
Johns Hopkins Bloomberg School of Public Health
University of Freiburg Medical Center
Merck
Loyola University Chicago
University Medical Centre Groningen
National Research Council of Italy
Bio4Dreams—Business Nursery for Life Sciences
National University of Singapore
GlaxoSmithKline
Leipzig University
University of Utah School of Medicine
IRCCS Ospedale Infantile Burlo Garofolo - Trieste
Boston University School of Public Health
University of Greifswald
Partner Site Munich
EURAC Research
University of Trento
Ludwig Maximilian University of Munich
National Institutes of Health
University of Maryland School of Medicine
University of Trieste
Leiden University Medical Centre
University of Iceland
Université de Lille
Medical University of Graz

Research output: Contribution to journal › Article › Academic › peer-review

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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_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.

Original language	English
Article number	580
Journal	Communications Biology
Volume	5
Issue number	1
DOIs	https://doi.org/10.1038/s42003-022-03448-z
Publication status	Published - 1 Dec 2022

Bibliographical note

Funding
Open Access funding enabled and organized by Projekt DEAL.

Publisher Copyright: © 2022, The Author(s).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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s42003-022-03448-zFinal published version, 5.55 MBLicence: CC BY

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Winkler, T. W., Rasheed, H., The LifeLines Cohort Study, DiscovEHR and MyCode Community Health Initiative, VA Million Veteran Program, Teumer, A., Gorski, M., Rowan, B. X., Stanzick, K. J., Thomas, L. F., Tin, A., Hoppmann, A., Chu, A. Y., Tayo, B., Thio, C. H. L., Cusi, D., Chai, J. F., Sieber, K. B., Horn, K., ... Wang, Y. X. (2022). Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals. Communications Biology, 5(1), Article 580. https://doi.org/10.1038/s42003-022-03448-z

@article{3a02af2375ef4509883766bc8e7d8da5,

title = "Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals",

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.",

author = "Winkler, \{Thomas W.\} and Humaira Rasheed and \{The LifeLines Cohort Study\} and \{DiscovEHR and MyCode Community Health Initiative\} and \{VA Million Veteran Program\} and Alexander Teumer and Mathias Gorski and Rowan, \{Bryce X.\} and Stanzick, \{Kira J.\} and Thomas, \{Laurent F.\} and Adrienne Tin and Anselm Hoppmann and Chu, \{Audrey Y.\} and Bamidele Tayo and Thio, \{Chris H.L.\} and Daniele Cusi and Chai, \{Jin Fang\} and Sieber, \{Karsten B.\} and Katrin Horn and Man Li and Markus Scholz and Massimiliano Cocca and Matthias Wuttke and \{van der Most\}, \{Peter J.\} and Qiong Yang and Sahar Ghasemi and Teresa Nutile and Yong Li and Giulia Pontali and Felix G{\"u}nther and Abbas Dehghan and Adolfo Correa and Afshin Parsa and Agnese Feresin and \{de Vries\}, \{Aiko P.J.\} and Zonderman, \{Alan B.\} and Smith, \{Albert V.\} and Oldehinkel, \{Albertine J.\} and \{De Grandi\}, Alessandro and Rosenkranz, \{Alexander R.\} and Fernando Rivadeneira and Helena Schmidt and Felix, \{Janine F.\} and Ikram, \{M. Arfan\} and Maryam Kavousi and Mohsen Ghanbari and Niek Verweij and Raymond Noordam and Sanaz Sedaghat and Suzanne Vogelezang and Wong, \{Tien Yin\} and Jaddoe, \{Vincent W.V.\} and Wang, \{Ya Xing\}",

note = "Funding Open Access funding enabled and organized by Projekt DEAL. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

day = "1",

doi = "10.1038/s42003-022-03448-z",

language = "English",

volume = "5",

journal = "Communications Biology",

issn = "2399-3642",

publisher = "Springer Nature",

number = "1",

}

Winkler, TW, Rasheed, H, The LifeLines Cohort Study, DiscovEHR and MyCode Community Health Initiative, VA Million Veteran Program, Teumer, A, Gorski, M, Rowan, BX, Stanzick, KJ, Thomas, LF, Tin, A, Hoppmann, A, Chu, AY, Tayo, B, Thio, CHL, Cusi, D, Chai, JF, Sieber, KB, Horn, K, Li, M, Scholz, M, Cocca, M, Wuttke, M, van der Most, PJ, Yang, Q, Ghasemi, S, Nutile, T, Li, Y, Pontali, G, Günther, F, Dehghan, A, Correa, A, Parsa, A, Feresin, A, de Vries, APJ, Zonderman, AB, Smith, AV, Oldehinkel, AJ, De Grandi, A, Rosenkranz, AR, Rivadeneira, F, Schmidt, H, Felix, JF , Ikram, MA , Kavousi, M , Ghanbari, M, Verweij, N, Noordam, R, Sedaghat, S, Vogelezang, S, Wong, TY, Jaddoe, VWV & Wang, YX 2022, 'Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals', Communications Biology, vol. 5, no. 1, 580. https://doi.org/10.1038/s42003-022-03448-z

TY - JOUR

T1 - Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals

AU - Winkler, Thomas W.

AU - Rasheed, Humaira

AU - The LifeLines Cohort Study

AU - DiscovEHR and MyCode Community Health Initiative

AU - VA Million Veteran Program

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 - Rivadeneira, Fernando

AU - Schmidt, Helena

AU - Felix, Janine F.

AU - Ikram, M. Arfan

AU - Kavousi, Maryam

AU - Ghanbari, Mohsen

AU - Verweij, Niek

AU - Noordam, Raymond

AU - Sedaghat, Sanaz

AU - Vogelezang, Suzanne

AU - Wong, Tien Yin

AU - Jaddoe, Vincent W.V.

AU - Wang, Ya Xing

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 - https://www.scopus.com/pages/publications/85131867525

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 -

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

Abstract

Bibliographical note

UN SDGs

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