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Abstract: FR-OR054

Genetic Determinants of CKD Progression Among Individuals Without Diabetes: The Million Veteran Program

Session Information

Category: CKD (Non-Dialysis)

  • 2101 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention

Authors

  • Robinson-Cohen, Cassianne, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Chen, Hua-Chang, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Tao, Ran, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Wilson, Otis D., Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Giri, Ayush, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Akwo, Elvis A., Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Chung, Cecilia P., Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Edwards, Todd L., Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Wilson, Peter W., Emory University, Atlanta, Georgia, United States
  • O'Donnell, Christopher Joseph, Boston Veterans Administration, Boston, Massachusetts, United States
  • Hung, Adriana, VA & Vanderbilt University, Nashville, Tennessee, United States

Group or Team Name

  • on behalf of the Million Veteran Program
Background

The rate of CKD progression among individuals with diabetes varies widely and is incompletely explained by known risk factors. While the genetic determinants of cross-sectional eGFR have been identified, only one small analysis of longitudinal change in eGFR among individuals with CKD has been conducted.

Methods

We performed a genome-wide association study of the relative rate of decline in estimated glomerular filtration rate (eGFR, % decline/year) among 41,348 individuals with CKD and free of diabetes at baseline participating in the Million Veteran Program. Analyses were stratified by race; 5,818 participants were of non-Hispanic Black race/ethnicity.

Results

Mean (SD) eGFR at baseline was 51.1 (±8.1) ml/min/1.73m2 and median relative kidney function decline was -0.7%/year. In trans-ethnic meta-analysis, we uncovered 48 SNPs from 2 independent regions associated with decline in kidney function. The SNP with the strongest association, rs13329952, is an intronic variant in UMOD; every additional minor allele was associated with a 1%/year faster decline in eGFR (p=1.7x10-13). Our GWAS also identified a novel locus associated with CKD progression (top SNP rs12805797 near LINC02098 (p=5.0x10-8)). Among blacks, the presence of two high-risk APOL1 variants was associated with a 3%/year faster decline in eGFR, relative to individuals with no high-risk variants.

Conclusion

Our data suggest that CKD progression has a genetic basis beyond that of baseline eGFR alone. Better understanding of the contribution of inherited genes to CKD progression could help to build the foundation for genetic diagnosis and personalized treatment of this common condition.

Funding

  • NIDDK Support