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

• Published in: American journal of nephrology Vol. 49; no. 3; pp. 193 - 202
• Main Authors: Thio, Chris H.L., Reznichenko, Anna, van der Most, Peter J., Kamali, Zoha, Vaez, Ahmad, Smit, Johannes H., Penninx, Brenda W.J.H., Haller, Toomas, Mihailov, Evelin, Metspalu, Andres, Damman, Jeffrey, de Borst, Martin H., van der Harst, Pim, Verweij, Niek, Navis, Gerjan J., Gansevoort, Ron T., Nolte, Ilja M., Snieder, Harold
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland 01.03.2019
• Subjects: Computational Biology; European Continental Ancestry Group - genetics; Genome-Wide Association Study; Humans; Kidney - metabolism; Metabolic Networks and Pathways - genetics; Original Report: Patient-Oriented, Translational Research; Polymorphism, Single Nucleotide; Quantitative Trait Loci; Reference Values; Urea - blood; Urea - metabolism; Serum urea; Kidney function; Genome-wide association studies
• ISSN: 0250-8095; 1421-9670
• DOI: 10.1159/000496930

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.