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American Heart Association, Circulation: Genomic and Precision Medicine, 4(13), 2020

DOI: 10.1161/circgen.119.002891

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

This paper was not found in any repository, but could be made available legally by the author.
This paper was not found in any repository, but could be made available legally by the author.

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Data provided by SHERPA/RoMEO

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.