Genome-Wide Association of Kidney Traits in Hispanics/Latinos Using Dense Imputed Whole-Genome Sequencing Data: The Hispanic Community Health Study/Study of Latinos

Circ Genom Precis Med. 2020 Aug;13(4):e002891. doi: 10.1161/CIRCGEN.119.002891. Epub 2020 Jun 29.

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.

Keywords: genes; genetic variation; genetics; genome-wide association study; kidney; population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Bcl-2-Like Protein 11 / genetics
  • Female
  • Gene Frequency
  • Genetic Variation
  • Genome-Wide Association Study*
  • Genotype
  • Glomerular Filtration Rate / genetics
  • Hispanic or Latino / genetics*
  • Humans
  • Kidney Diseases / genetics*
  • Kidney Diseases / pathology
  • Male
  • Middle Aged
  • Promyelocytic Leukemia Zinc Finger Protein / genetics
  • RNA Helicases / genetics
  • Whole Genome Sequencing

Substances

  • BCL2L11 protein, human
  • Bcl-2-Like Protein 11
  • Promyelocytic Leukemia Zinc Finger Protein
  • ZBTB16 protein, human
  • AQR protein, human
  • RNA Helicases