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.
Glomerular Filtration Rate and Urine Albumin to Creatinine Ratio Associated With Hearing Impairment Among Korean Adults With Diabetes
