Polygenic risk scores and kidney traits in the Hispanic/Latino population: The Hispanic Community Health Study/Study of Latinos

Abstract

Estimated glomerular filtration rate (eGFR) is used to evaluate kidney function and determine the presence of chronic kidney disease (CKD), a highly prevalent disease in the US^{1 , 2 , 3} that varies among subgroups of Hispanic/Latino individuals.^{4 , 5} The polygenic risk score (PRS) is a popular method that uses large genome-wide association studies (GWASs) to provide a strong estimate of disease risk.⁷ However, due to the limited availability of summary statistics from GWAS meta-analyses based on Hispanic/Latino populations, PRSs can only be computed using different ancestry GWASs. The performance of eGFR PRSs derived from other GWAS reference populations for Hispanic/Latino population has not been examined. We compared PRS constructions for eGFR prediction in Hispanic/Latino individuals using GWAS-significant variants, clumping and thresholding (C&T),⁸ and PRS-CS,²² as well as a combination of PRSs calculated with different reference GWAS meta-analyses from European and multi-ethnic studies in Hispanic/Latino individuals from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). All eGFR PRSs were highly associated with eGFR (p < 1E-20). Additionally, eGFR PRSs were significantly associated with lower risk of prevalent CKD at visit 1 or 2 and incident CKD at visit 2, with the combined PRSs having the best performance. These PRS findings were replicated in an additional dataset of Hispanic/Latino individuals using data from the Women's Health Initiative SNP Health Association Resource (WHI-SHARe).¹⁷.

Keywords: CKD; GWAS; HCHS/SOL; Hispanic/Latino population; PRS; admixed; eGFR; kidney traits.