Evaluating the predictive utility of European-based and transethnic polygenic risk scores for kidney function in older Black adults: insights from the Health and Retirement Study.

BACKGROUND: Black populations in the U.S. experience a disproportionately faster progression of chronic kidney disease than the general population. Polygenic risk scores (PRS) are a promising tool for risk stratification, yet their utility in predicting kidney function across populations remains uncertain.

METHODS: This study evaluates the effectiveness of European and trans-ethnic PRS in predicting kidney function among older Black adults from the 2010-2012 Health and Retirement Study (HRS) (N = 2080), a nationally representative sample of adults aged ≥50 years in the U.S. We assessed kidney function using an estimated glomerular filtration rate derived from cystatin C. The HRS constructed PRS from genome-wide association studies based on European and trans-ethnic ancestries. We used ordinary least-squares regression to examine the predictive power of European-based and transethnic PRS on kidney function, adjusting for demographic, behavioral, cardiometabolic risk, and socioeconomic factors.

RESULTS: The mean kidney function is approximately 74 mL/min/1.73 m2, with a wide range, indicating significant heterogeneity among older Black adults. Findings suggest that neither the European nor the trans-ethnic PRS demonstrated a significant association with kidney function in demographic-adjusted models among older Black adults. Including behavioral, cardiometabolic, and socioeconomic factors did not change this relationship.

CONCLUSIONS: Our findings underscore the challenges of applying PRS to predict kidney function among older Black adults. They also emphasize the need for more inclusive genomic research and the significant impact of clinical and sociodemographic factors on kidney function among older Black adults. These insights are vital for enhancing precision medicine and ensuring equitable genomic practices.