Genome-Wide Association of Kidney Traits in Hispanics/Latinos Using Dense Imputed Whole-Genome Sequencing Data

Abstract

Background: Genetic factors that influence kidney traits have been understudied for low-frequency and ancestry-specific variants. Methods: This study used imputed whole-genome sequencing from the Trans-Omics for Precision Medicine project to identify novel loci for estimated glomerular filtration rate and urine albumin-to-creatinine ratio in up to 12 207 Hispanics/Latinos. Replication was performed in the Women’s Health Initiative and the UK Biobank when variants were available. Results: Two low-frequency intronic variants were associated with estimated glomerular filtration rate (rs58720902 at AQR , minor allele frequency=0.01, P =1.6×10 −8 ) or urine albumin-to-creatinine ratio (rs527493184 at ZBTB16 , minor allele frequency=0.002, P =1.1×10 −8 ). An additional variant at PRNT (rs2422935, minor allele frequency=0.54, P =2.89×10 −8 ) was significantly associated with estimated glomerular filtration rate in meta-analysis with replication samples. We also identified 2 known loci for urine albumin-to-creatinine ratio ( BCL2L11 rs116907128, P =5.6×10 −8 and HBB rs344, P =9.3×10 −11 ) and validated 8 loci for urine albumin-to-creatinine ratio previously identified in the UK Biobank. Conclusions: Our study shows gains in gene discovery when using dense imputation from multi-ethnic whole-genome sequencing data in admixed Hispanics/Latinos. It also highlights limitations in genetic research of kidney traits, including the lack of suitable replication samples for variants that are more common in non-European ancestry and those at low frequency in populations.