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Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals
Thomas W Winkler1, Humaira Rasheed2,3,4, Alexander Teumer5,6,7
1Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany. thomas.winkler@ukr.de.
Communications Biology
|June 13, 2022
Summary
Genetic factors influencing kidney function differ between individuals with and without diabetes mellitus (DM). Most genetic effects on estimated glomerular filtration rate (eGFR) are shared, suggesting broad effectiveness for kidney disease drug interventions.
Area of Science:
- Genetics
- Nephrology
- Metabolic Diseases
Background:
- Reduced glomerular filtration rate (GFR) is a precursor to kidney failure.
- Genetics and diabetes mellitus (DM) are known risk factors for kidney disease, but their interaction is poorly understood.
Purpose of the Study:
- To investigate genetic influences on estimated GFR (eGFR) in relation to DM status.
- To identify genetic loci affecting eGFR differently in individuals with and without DM.
- To explore potential therapeutic targets for kidney disease.
Main Methods:
- Genome-wide association meta-analyses of eGFR were performed separately for individuals with and without DM.
- Large cohorts were analyzed: nDM = 178,691 and nnoDM = 1,296,113.
- Gene prioritization was employed to identify potential drug targets.
Main Results:
- Seven eGFR loci showed significant differences between DM and noDM groups.
- Four novel loci with suggestive differences and 28 additional novel loci were identified.
- Genome-wide association studies in DM individuals identified loci associated with diabetic kidney disease, highlighting 18 genes for drug development.
Conclusions:
- Most genetic effects on eGFR are shared between individuals with and without DM, indicating potential for broadly effective interventions.
- Specific genetic effects unique to DM or noDM status were identified, informing targeted drug development.
- The findings provide insights into the genetic architecture of kidney function and diabetic kidney disease.
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