Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline
Mathias Gorski1, Bettina Jung2, Yong Li3
1Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany; Department of Nephrology, University Hospital Regensburg, Regensburg, Germany.
Kidney International
|November 2, 2020
Summary
This study identified novel genetic loci associated with rapid kidney function decline, offering potential therapeutic targets. High genetic risk for rapid decline increases the risk of acute kidney injury.
Area of Science:
- Nephrology
- Genetics
- Genomics
Background:
- Rapid decline in estimated glomerular filtration rate (eGFRcrea) is linked to adverse clinical outcomes.
- The genetic underpinnings of rapid eGFRcrea decline remain largely uncharacterized.
Purpose of the Study:
- To identify genetic loci associated with rapid estimated glomerular filtration rate decline.
- To explore the genetic basis of kidney function deterioration.
Main Methods:
- Meta-analysis of 42 genome-wide association studies from the CKDGen Consortium and UK Biobank.
- Defined rapid eGFRcrea decline using two criteria: "Rapid3" (≥3 mL/min/1.73m²/year) and "CKDi25" (≥25% decline in eGFRcrea).
- Bioinformatic analyses to prioritize variants and genes at identified loci.
Main Results:
- Seven independent variants across six loci were identified for rapid eGFRcrea decline (Rapid3 and/or CKDi25).
- Five variants at four loci (near UMOD-PDILT, PRKAG2, WDR72, OR2S2) reached genome-wide significance.
- High genetic risk for rapid decline was associated with a 1.20-fold increased risk of acute kidney injury.
Conclusions:
- Novel genetic loci for rapid kidney function decline were discovered.
- These findings may aid in identifying therapeutic targets and understanding mechanisms of kidney function deterioration.
- Genetic risk profiling could help identify individuals susceptible to sustained kidney function decline.
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