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Kidney Week

Abstract: PO1629

Epigenome-wide Association Study of Kidney Function

Session Information

Category: Genetic Diseases of the Kidneys

  • 1002 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Franceschini, Nora, University of North Carolina System, Chapel Hill, North Carolina, United States
  • Breeze, Charles E., UCL Cancer Institute, University College London, London, United Kingdom
  • Mychaleckyj, Josyf, University of Virginia, Charlottesville, Virginia, United States

Group or Team Name

  • COGENT-KIDNEY Consortium
Background

DNA methylation regulates gene regulation and may influence estimated glomerular filtration rate (eGFR).

Methods

The study included over 13,000 participants from multi-ethnic studies for discovery and replication. We tested the associations between whole blood DNA methylation and eGFR using normalized beta values from Illumina 450K or EPIC arrays. Analyses were performed in study- and race-stratified samples using linear mixed models and adjusting for age, sex, and study-specific and technical variables. Study-specific results were meta-analyzed, and findings were assessed using integrative epigenomics methods and pathway analyses.

Results

The study identified 93 DMPs genome-wide significantly associated with eGFR, of which 35 replicated in independent samples. We also replicated 6 previously published DMPs including the ZNF20-ZNF788 locus. Identified DMPs showed significant overlap enrichment with DNase I hypersensitive sites in kidney tissue, sites associated with the expression of genes in cis, and transcription factor motifs, in addition to pathways associated with kidney development. Among main findings, we identified a DMP at the KANK1 gene, which has been previously associated with podocyte dysfunction and nephrotic syndrome.

Conclusion

We identified DMPs associated with eGFR and uncovered associations with genomic regions related to regulatory function in kidney tissue. These findings shed light on epigenetic mechanisms associated with kidney function, bridging the gap between eGFR-associated DNA methylation and tissue-specific chromatin context.

Funding

  • NIDDK Support