A methylation risk score for chronic kidney disease: a HyperGEN study

Area of Science:

• Nephrology
• Epigenetics
• Genomics

Background:

• Chronic kidney disease (CKD) disproportionately affects African Americans (AAs).
• Epigenetic modifications, specifically DNA methylation at cytosine-phosphate-guanine (CpG) sites, are linked to kidney function.
• AAs may exhibit heightened sensitivity to environmental factors influencing methylation patterns relevant to CKD.

Purpose of the Study:

• To develop and validate a methylation risk score (MRS) for predicting prevalent CKD in African American cohorts.
• To assess the clinical utility of an MRS based on CpG methylation sites associated with estimated glomerular filtration rate (eGFR).

Main Methods:

• Selected nine CpG sites previously associated with eGFR from epigenome-wide association studies.
• Constructed a MRS using these CpG sites within the Hypertension Genetic Epidemiology Network (HyperGEN) cohort.
• Validated the MRS in independent cohorts using logistic mixed models and sensitivity analyses.

Main Results:

• The developed MRS was significantly associated with prevalent CKD in logistic mixed models.
• The association remained robust across multiple sensitivity analyses, accounting for known CKD risk factors.
• Modest replication of the MRS predictive capability was observed in validation cohorts.

Conclusions:

• An eGFR-based CpG methylation risk score (MRS) independently predicts prevalent CKD.
• The MRS demonstrates potential for clinical utility in assessing CKD risk and progression.
• Further investigation is warranted to explore the clinical application of this epigenetic biomarker in diverse populations.