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Abstract: SA-PO634

African and European Ancestry Proportions Are Associated with eGFR Measures in Over 270,000 Participants from the Million Veterans Program (MVP)

Session Information

Category: Genetic Diseases of the Kidney

  • 803 Genetic Epidemiology and Other Genetic Studies of Common Kidney Diseases

Authors

  • Velez edwards, Digna R, Vanderbilt University, Nashville, Tennessee, United States
  • Giri, Ayush, Vanderbilt University, Nashville, Tennessee, United States
  • Torstenson, Eric S, Vanderbilt University, Nashville, Tennessee, United States
  • Hellwege, Jacklyn N, Vanderbilt University, Nashville, Tennessee, United States
  • Kovesdy, Csaba P., University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • O'Donnell, Christopher Joseph, Boston Veterans Administration, Boston, Massachusetts, United States
  • Edwards, Todd L., Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Hung, Adriana, Vanderbilt University, Nashville, Tennessee, United States

Group or Team Name

  • On behalf of VA Million Veteran Program
Background

Current methods estimate glomerular filtration rate (eGFR) using a creatinine based equation. Because African Americans have higher muscle mass and creatinine generation, current eGFR equations incorporate a dichotomous indicator for race (black/not black). It is unclear if this measure appropriately accounts for eGFR variability due to genetic ancestry.

Methods

To determine whether ancestry proportions influence eGFR, we evaluated associations between genetically inferred proportions of ancestry relative to 5 reference populations (GBR, PEL, YRI, CHB, and LWK) and eGFR in 56,237 self-reported blacks and 216,528 self-reported whites from the MVP. Traits were modeled using linear regression against each ancestry proportion variable adjusted for important covariates to report estimates per 10% increase for a given inferred ancestry percentage in whites and blacks separately.

Results

In self-reported blacks, every 10% increase in GBR ancestry was associated with 1.1 unit increase in eGFR levels (p-value = 5x10-76), while 10% increase in Yoruban ancestry was inversely associated with eGFR (beta: -1.1; p-value = 1x10-88). The virtually identical magnitude of effect estimates is consistent with the known two-way European/African admixture observed in blacks from the United States. Interestingly, despite the small contribution of Native American (estimated using Peruvian (PEL)) admixture to this group, PEL ancestry was positively associated with eGFR (beta: 2.16; p-value = 1.2x10-9); with the largest effect estimates observed in non-diabetic blacks. Neither CHB nor LWK ancestry was associated with eGFR in blacks (p-values >0.05). In Whites, PEL ancestry was positively associated with eGFR (beta = 0.63; p-value = 2.5x10-21), while both African ancestry proportions were inversely associated (YRI beta = -0.86, p-value = 8x10-29; LWK beta = -3.10, p-value = 8x10-39).

Conclusion

Overall, Yoruban ancestry strongly associates with decreased eGFR in both whites and blacks, after accounting for dichotomous race in the eGFR equation. Since eGFR is a strong predictor of end stage renal disease, our results suggest incorporating ancestry proportion information into eGFR calculations may provide a better predictor for future disease risk.

Funding

  • Veterans Affairs Support