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

doi:10.1159/000496930

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

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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 language	English
Pages (from-to)	193-202
Number of pages	10
Journal	American Journal of Nephrology
Volume	49
Issue number	3
DOIs	https://doi.org/10.1159/000496930
Publication status	Published - 2019

Keywords

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

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Genome-Wide Association Scan of Serum Urea in European Populations Identifies Two Novel LociFinal publisher's version, 383 KBLicence: CC BY-NC-ND

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TransplantLines
Bakker, S. (Creator), Leuvenink, H. G. D. (Creator) & Porte, R. J. (Creator), University of Groningen, 2017
http://www.transplantlines.umcg.nl
Dataset
Prevention of Renal and Vascular End-stage Disease (PREVEND)
Gansevoort, R. T. (Creator), University of Groningen, 2017
https://www.umcg.nl/EN/Research/Researchers/Facilities/biobanks/biobanks/prevend/Paginas/default.aspx#
Dataset
Supplementary Material for: Genome-Wide Association Scan of Serum Urea in European Populations Identifies Two Novel Loci
Thio, C. (Contributor), Reznichenko, A. (Creator), Kamali, Z. (Creator), Vaez Barzani, A. (Creator), Smit, J. H. (Creator), Penninx, B. W. J. H. (Contributor), Haller, T. (Creator), Mihailov, E. (Creator), Metspalu, A. (Creator), Damman, J. (Creator), Verweij, N. (Creator), Navis, G. (Creator), Gansevoort, R. (Creator), Nolte, I. M. (Creator) & Snieder, H. (Creator), Karger Publishers, 26-Feb-2019
DOI: 10.6084/m9.figshare.7764974, https://karger.figshare.com/articles/Supplementary_Material_for_Genome-Wide_Association_Scan_of_Serum_Urea_in_European_Populations_Identifies_Two_Novel_Loci/7764974
Dataset

Cite this

Lifelines Cohort Study group, Thio, C. H. L., Reznichenko, A., van der Most, P. J., Kamali, Z., Vaez, A., Smit, J. H., Penninx, B. W. J. H., Haller, T., Mihailov, E., Metspalu, A., Damman, J., de Borst, M. H., van der Harst, P., Verweij, N., Navis, G. J., Gansevoort, R. T., Nolte, I. M., & Snieder, H. (2019). Genome-Wide Association Scan of Serum Urea in European Populations Identifies Two Novel Loci. American Journal of Nephrology, 49(3), 193-202. https://doi.org/10.1159/000496930

@article{66609062a8ff485d8c56d708d01763d4,

title = "Genome-Wide Association Scan of Serum Urea in European Populations Identifies Two Novel Loci",

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.",

keywords = "Genome-wide association studies, Serum urea, Kidney function, KIDNEY-FUNCTION, RENAL-FUNCTION, METAANALYSIS, SUSCEPTIBILITY, HAPLOTYPES, TRAITS, TARGET, TOOL, MAP",

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

note = "{\textcopyright} 2019 The Author(s) Published by S. Karger AG, Basel.",

year = "2019",

doi = "10.1159/000496930",

language = "English",

volume = "49",

pages = "193--202",

journal = "American Journal of Nephrology",

issn = "0250-8095",

publisher = "KARGER",

number = "3",

}

Lifelines Cohort Study group, Thio, CHL, Reznichenko, A, van der Most, PJ , Kamali, Z , Vaez, A, Smit, JH, Penninx, BWJH, Haller, T, Mihailov, E, Metspalu, A, Damman, J, de Borst, MH , van der Harst, P, Verweij, N, Navis, GJ , Gansevoort, RT , Nolte, IM & Snieder, H 2019, 'Genome-Wide Association Scan of Serum Urea in European Populations Identifies Two Novel Loci', American Journal of Nephrology, vol. 49, no. 3, pp. 193-202. https://doi.org/10.1159/000496930

TY - JOUR

T1 - Genome-Wide Association Scan of Serum Urea in European Populations Identifies Two Novel Loci

AU - Lifelines Cohort Study group

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 - Serum urea

KW - Kidney function

KW - KIDNEY-FUNCTION

KW - RENAL-FUNCTION

KW - METAANALYSIS

KW - SUSCEPTIBILITY

KW - HAPLOTYPES

KW - TRAITS

KW - TARGET

KW - TOOL

KW - MAP

U2 - 10.1159/000496930

DO - 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

IS - 3

ER -

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

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Datasets

TransplantLines

Prevention of Renal and Vascular End-stage Disease (PREVEND)

Supplementary Material for: Genome-Wide Association Scan of Serum Urea in European Populations Identifies Two Novel Loci

Cite this