Genome-Wide Association Scan of Serum Urea in European Populations Identifies Two Novel Loci

Lifelines Cohort Study group, Chris H L Thio, Anna Reznichenko, Peter J van der Most, Zoha Kamali, Ahmad Vaez, Johannes H Smit, Brenda W J H Penninx, Toomas Haller, Evelin Mihailov, Andres Metspalu, Jeffrey Damman, Martin H de Borst, Pim van der Harst, Niek Verweij, Gerjan J Navis, Ron T Gansevoort, Ilja M Nolte, Harold Snieder

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)
194 Downloads (Pure)

Abstract

BACKGROUND: Serum urea level is a heritable trait, commonly used as a diagnostic marker for kidney function. Genome-wide association studies (GWAS) in East-Asian populations identified a number of genetic loci related to serum urea, however there is a paucity of data for European populations.

METHODS: We performed a two-stage meta-analysis of GWASs on serum urea in 13,312 participants, with independent replication in 7,379 participants of European ancestry.

RESULTS: We identified 6 genome-wide significant single nucleotide polymorphisms (SNPs) in or near 6 loci, of which 2 were novel (POU2AF1 and ADAMTS9-AS2). Replication of East-Asian and Scottish data provided evidence for an additional 8 loci. SNPs tag regions previously associated with anthropometric traits, serum magnesium, and urinary albumin-to-creatinine ratio, as well as expression quantitative trait loci for genes preferentially expressed in kidney and gastro-intestinal tissues.

CONCLUSIONS: Our findings provide insights into the genetic underpinnings of urea metabolism, with potential relevance to kidney function.

Original languageEnglish
Pages (from-to)193-202
Number of pages10
JournalAmerican Journal of Nephrology
Volume49
Issue number3
DOIs
Publication statusPublished - 2019

Keywords

  • Genome-wide association studies
  • Serum urea
  • Kidney function
  • KIDNEY-FUNCTION
  • RENAL-FUNCTION
  • METAANALYSIS
  • SUSCEPTIBILITY
  • HAPLOTYPES
  • TRAITS
  • TARGET
  • TOOL
  • MAP

Cite this