Genome-Wide Association Scan of serum urea in European populations identifies two novel loci

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

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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
JournalAmerican Journal of Nephrology
Publication statusPublished - 2019


  • Genome-wide association studies
  • Kidney function
  • Serum urea

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