TY - JOUR
T1 - Genome-Wide Association Scan of serum urea in European populations identifies two novel loci
AU - Thio, Chris H. L.
AU - Reznichenko, Anna
AU - van der Most, Peter J.
AU - Kamali, Zoha
AU - Vaez, Ahmad
AU - Smit, Johannes H.
AU - Penninx, Brenda W. J. H.
AU - Haller, Toomas
AU - Mihailov, Evelin
AU - Metspalu, Andres
AU - Damman, Jeffrey
AU - de Borst, Martin H.
AU - van der Harst, Pim
AU - Verweij, Niek
AU - Navis, Gerjan J.
AU - Gansevoort, Ron T.
AU - Nolte, Ilja M.
AU - Snieder, Harold
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
KW - Genome-wide association studies
KW - Kidney function
KW - Serum urea
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85062431379&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30808845
U2 - https://doi.org/10.1159/000496930
DO - https://doi.org/10.1159/000496930
M3 - Article
C2 - 30808845
SN - 0250-8095
VL - 49
SP - 193
EP - 202
JO - American Journal of Nephrology
JF - American Journal of Nephrology
ER -