Mapping eGFR loci to the renal transcriptome and phenome in the VA Million Veteran Program

Nat Commun. 2019 Aug 26;10(1):3842. doi: 10.1038/s41467-019-11704-w.


Chronic kidney disease (CKD), defined by low estimated glomerular filtration rate (eGFR), contributes to global morbidity and mortality. Here we conduct a transethnic Genome-Wide Association Study of eGFR in 280,722 participants of the Million Veteran Program (MVP), with replication in 765,289 participants from the Chronic Kidney Disease Genetics (CKDGen) Consortium. We identify 82 previously unreported variants, confirm 54 loci, and report interesting findings including association of the sickle cell allele of betaglobin among non-Hispanic blacks. Our transcriptome-wide association study of kidney function in healthy kidney tissue identifies 36 previously unreported and nine known genes, and maps gene expression to renal cell types. In a Phenome-Wide Association Study in 192,868 MVP participants using a weighted genetic score we detect associations with CKD stages and complications and kidney stones. This investigation reinterprets the genetic architecture of kidney function to identify the gene, tissue, and anatomical context of renal homeostasis and the clinical consequences of dysregulation.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Animals
  • Cell Line
  • Chromosome Mapping / methods*
  • Cohort Studies
  • Computational Biology
  • Female
  • Genetic Loci
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Glomerular Filtration Rate / genetics*
  • Humans
  • Kidney / cytology
  • Kidney / metabolism
  • Kidney / physiopathology*
  • Male
  • Mice
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • RNA-Seq
  • Renal Insufficiency, Chronic / genetics*
  • Renal Insufficiency, Chronic / physiopathology
  • Transcriptome / genetics*
  • United States
  • United States Department of Veterans Affairs
  • Veterans