Kidney Week

Abstract: FR-OR054

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

Session Information

• Genes, Environment, and Lifestyle: Risk Factors for CKD
  November 08, 2019 | Location: Salon C, Walter E. Washington Convention Center
  Abstract Time: 05:06 PM - 05:18 PM

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

Cassianne Robinson-Cohen, PhD



Cassianne Robinson-Cohen, PhD, is Assistant Professor in the Division of Nephrology at Vanderbilt University Medical Center. She is an epidemiologist interested in understanding genetic and environmental risk factors for chronic kidney disease progression, mineral metabolism disorders and cardiovascular complications.

• Chen, Hua-Chang, Vanderbilt University Medical Center, Nashville, Tennessee, United States

Hua-Chang Chen,

• Tao, Ran, Vanderbilt University Medical Center, Nashville, Tennessee, United States

Ran Tao,

• Wilson, Otis D., Vanderbilt University Medical Center, Nashville, Tennessee, United States

Otis D. Wilson,

• Giri, Ayush, Vanderbilt University Medical Center, Nashville, Tennessee, United States

Ayush Giri,

• Akwo, Elvis A., Vanderbilt University Medical Center, Nashville, Tennessee, United States

Elvis A. Akwo,

• Chung, Cecilia P., Vanderbilt University Medical Center, Nashville, Tennessee, United States

Cecilia P. Chung,

• Edwards, Todd L., Vanderbilt University Medical Center, Nashville, Tennessee, United States

Todd L. Edwards,

• Wilson, Peter W., Emory University, Atlanta, Georgia, United States

Peter W. Wilson,

• O'Donnell, Christopher Joseph, Boston Veterans Administration, Boston, Massachusetts, United States

Christopher Joseph O'Donnell,

• Hung, Adriana, VA & Vanderbilt University, Nashville, Tennessee, United States

Adriana Hung,

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