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

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LifeLines Cohort Study , DiscovEHR MyCode Study , VA Million Vet Program , LifeLines Cohort Study , DiscovEHR MyCode Study , VA Million Vet Program , Winkler , T W , Rasheed , H , Teumer , A , Perola , M , Salomaa , V & Kuokkanen , M 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

Title: Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals
Author: LifeLines Cohort Study; DiscovEHR MyCode Study; VA Million Vet Program; LifeLines Cohort Study; DiscovEHR MyCode Study; VA Million Vet Program; Winkler, Thomas W.; Rasheed, Humaira; Teumer, Alexander; Perola, Markus; Salomaa, Veikko; Kuokkanen, Mikko
Contributor organization: University of Helsinki
CAMM - Research Program for Clinical and Molecular Metabolism
Faculty of Medicine
Research Programs Unit
Date: 2022-06-13
Language: eng
Number of pages: 20
Belongs to series: Communications Biology
ISSN: 2399-3642
DOI: https://doi.org/10.1038/s42003-022-03448-z
URI: http://hdl.handle.net/10138/346327
Abstract: A large-scale GWAS provides insight on diabetes-dependent genetic effects on the glomerular filtration rate, a common metric to monitor kidney health in disease. 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.
Subject: GENOME-WIDE ASSOCIATION
ENVIRONMENT INTERACTION
QUALITY-CONTROL
METAANALYSIS
LOCI
JOINT
EFFICIENT
SMOKING
DISEASE
EXPRESSION
3111 Biomedicine
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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