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

被引：6

作者：

Thio, Chris H. L. ^{[1
]}

Reznichenko, Anna ^{[2
]}

van der Most, Peter J. ^{[1
]}

Kamali, Zoha ^{[3
]}

Vaez, Ahmad ^{[1
,3
]}

Smit, Johannes H. ^{[5
,6
]}

Penninx, Brenda W. J. H. ^{[5
,6
]}

Haller, Toomas ^{[7
]}

Mihailov, Evelin ^{[7
]}

Metspalu, Andres ^{[7
]}

Damman, Jeffrey ^{[8
,10
]}

de Borst, Martin H. ^{[2
,8
]}

van der Harst, Pim ^{[9
,11
]}

Verweij, Niek ^{[9
,11
]}

Navis, Gerjan J. ^{[2
,9
]}

Gansevoort, Ron T. ^{[2
,9
]}

Nolte, Ilja M. ^{[1
]}

Snieder, Harold ^{[1
]}

机构：

[1] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands

[2] Univ Groningen, Univ Med Ctr Groningen, Dept Nephrol, Groningen, Netherlands

[3] Isfahan Univ Med Sci, Dept Bioinformat, Esfahan, Iran

[4] Lifelines Cohort Study & Biobank, Groningen, Netherlands

[5] GGZ inGeest, Netherlands Study Depress & Anxiety NESDA, Amsterdam, Netherlands

[6] Vrije Univ Amsterdam Med Ctr, Dept Psychiat, Amsterdam, Netherlands

[7] EGCUT, Inst Genom, Tartu, Estonia

[8] Univ Groningen, Univ Med Ctr Groningen, TransplantLines, Groningen, Netherlands

[9] Prevent REnal & Vasc ENdstage Dis PREVEND Cohort, Groningen, Netherlands

[10] Erasmus MC, Dept Pathol, Rotterdam, Netherlands

[11] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands

来源：

AMERICAN JOURNAL OF NEPHROLOGY | 2019年 / 49卷 / 03期

关键词：

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

D O I：

10.1159/000496930

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

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. (C) 2019 The Author(s) Published by S. Karger AG, Basel

引用

页码：193 / 202

页数：10

共 48 条

[1] A method and server for predicting damaging missense mutations [J].

Adzhubei, Ivan A. ;

Schmidt, Steffen ;

Peshkin, Leonid ;

Ramensky, Vasily E. ;

Gerasimova, Anna ;

Bork, Peer ;

Kondrashov, Alexey S. ;

Sunyaev, Shamil R. .

NATURE METHODS, 2010, 7 (04) :248-249

[2] A map of human genome variation from population-scale sequencing [J].

Altshuler, David ;

Durbin, Richard M. ;

Abecasis, Goncalo R. ;

Bentley, David R. ;

Chakravarti, Aravinda ;

Clark, Andrew G. ;

Collins, Francis S. ;

De la Vega, Francisco M. ;

Donnelly, Peter ;

Egholm, Michael ;

Flicek, Paul ;

Gabriel, Stacey B. ;

Gibbs, Richard A. ;

Knoppers, Bartha M. ;

Lander, Eric S. ;

Lehrach, Hans ;

Mardis, Elaine R. ;

McVean, Gil A. ;

Nickerson, DebbieA. ;

Peltonen, Leena ;

Schafer, Alan J. ;

Sherry, Stephen T. ;

Wang, Jun ;

Wilson, Richard K. ;

Gibbs, Richard A. ;

Deiros, David ;

Metzker, Mike ;

Muzny, Donna ;

Reid, Jeff ;

Wheeler, David ;

Wang, Jun ;

Li, Jingxiang ;

Jian, Min ;

Li, Guoqing ;

Li, Ruiqiang ;

Liang, Huiqing ;

Tian, Geng ;

Wang, Bo ;

Wang, Jian ;

Wang, Wei ;

Yang, Huanming ;

Zhang, Xiuqing ;

Zheng, Huisong ;

Lander, Eric S. ;

Altshuler, David L. ;

Ambrogio, Lauren ;

Bloom, Toby ;

Cibulskis, Kristian ;

Fennell, Tim J. ;

Gabriel, Stacey B. .

NATURE, 2010, 467 (7319) :1061-1073

[3] Elevated blood urea nitrogen level as a predictor of mortality in patients admitted for decompensated heart failure [J].

Aronson, D ;

Mittlernan, MA ;

Burger, AJ .

AMERICAN JOURNAL OF MEDICINE, 2004, 116 (07) :466-473

[4]

Baum N, 1975, Urology, V5, P583

[5] Genetic loci influencing kidney function and chronic kidney disease [J].

Chambers, John C. ;

Zhang, Weihua ;

Lord, Graham M. ;

van der Harst, Pim ;

Lawlor, Debbie A. ;

Sehmi, Joban S. ;

Gale, Daniel P. ;

Wass, Mark N. ;

Ahmadi, Kourosh R. ;

Bakker, Stephan J. L. ;

Beckmann, Jacqui ;

Bilo, Henk J. G. ;

Bochud, Murielle ;

Brown, Morris J. ;

Caulfield, Mark J. ;

Connell, John M. C. ;

Cook, H. Terence ;

Cotlarciuc, Ioana ;

Smith, George Davey ;

de Silva, Ranil ;

Deng, Guohong ;

Devuyst, Olivier ;

Dikkeschei, Lambert D. ;

Dimkovic, Nada ;

Dockrell, Mark ;

Dominiczak, Anna ;

Ebrahim, Shah ;

Eggermann, Thomas ;

Farrall, Martin ;

Ferrucci, Luigi ;

Floege, Jurgen ;

Forouhi, Nita G. ;

Gansevoort, Ron T. ;

Han, Xijin ;

Hedblad, Bo ;

van der Heide, Jaap J. Homan ;

Hepkema, Bouke G. ;

Hernandez-Fuentes, Maria ;

Hypponen, Elina ;

Johnson, Toby ;

de Jong, Paul E. ;

Kleefstra, Nanne ;

Lagou, Vasiliki ;

Lapsley, Marta ;

Li, Yun ;

Loos, Ruth J. F. ;

Luan, Jian'an ;

Luttropp, Karin ;

Marechal, Celine ;

Melander, Olle .

NATURE GENETICS, 2010, 42 (05) :373-375

[6] ADAMTS9, a novel member of the ADAM-TS/metallospondin gene family [J].

Clark, ME ;

Kelner, GS ;

Turbeville, LA ;

Boyer, A ;

Arden, KC ;

Maki, RA .

GENOMICS, 2000, 67 (03) :343-350

[7] Hypoxia and Complement-and-Coagulation Pathways in the Deceased Organ Donor as the Major Target for Intervention to Improve Renal Allograft Outcome [J].

Damman, Jeffrey ;

Bloks, Vincent W. ;

Daha, Mohamed R. ;

van der Most, Peter J. ;

Sanjabi, Bahram ;

van der Vlies, Pieter ;

Snieder, Harold ;

Ploeg, Rutger J. ;

Krikke, Christina ;

Leuvenink, Henri G. D. ;

Seelen, Marc A. .

TRANSPLANTATION, 2015, 99 (06) :1293-1300

[8]

Dirkx TC, 2019, CURRENT MED DIAGNOSI

[9] A second generation human haplotype map of over 3.1 million SNPs [J].

Frazer, Kelly A. ;

Ballinger, Dennis G. ;

Cox, David R. ;

Hinds, David A. ;

Stuve, Laura L. ;

Gibbs, Richard A. ;

Belmont, John W. ;

Boudreau, Andrew ;

Hardenbol, Paul ;

Leal, Suzanne M. ;

Pasternak, Shiran ;

Wheeler, David A. ;

Willis, Thomas D. ;

Yu, Fuli ;

Yang, Huanming ;

Zeng, Changqing ;

Gao, Yang ;

Hu, Haoran ;

Hu, Weitao ;

Li, Chaohua ;

Lin, Wei ;

Liu, Siqi ;

Pan, Hao ;

Tang, Xiaoli ;

Wang, Jian ;

Wang, Wei ;

Yu, Jun ;

Zhang, Bo ;

Zhang, Qingrun ;

Zhao, Hongbin ;

Zhao, Hui ;

Zhou, Jun ;

Gabriel, Stacey B. ;

Barry, Rachel ;

Blumenstiel, Brendan ;

Camargo, Amy ;

Defelice, Matthew ;

Faggart, Maura ;

Goyette, Mary ;

Gupta, Supriya ;

Moore, Jamie ;

Nguyen, Huy ;

Onofrio, Robert C. ;

Parkin, Melissa ;

Roy, Jessica ;

Stahl, Erich ;

Winchester, Ellen ;

Ziaugra, Liuda ;

Altshuler, David ;

Shen, Yan .

NATURE, 2007, 449 (7164) :851-U3

[10] 1000 Genomes-based meta-analysis identifies 10 novel loci for kidney function [J].

Gorski, Mathias ;

Van der Most, Peter J. ;

Teumer, Alexander ;

Chu, Audrey Y. ;

Li, Man ;

Mijatovic, Vladan ;

Nolte, Ilja M. ;

Cocca, Massimiliano ;

Taliun, Daniel ;

Gomez, Felicia ;

Li, Yong ;

Tayo, Bamidele ;

Tin, Adrienne ;

Feitosa, Mary F. ;

Aspelund, Thor ;

Attia, John ;

Biffar, Reiner ;

Bochud, Murielle ;

Boerwinkle, Eric ;

Borecki, Ingrid ;

Bottinger, Erwin P. ;

Chen, Ming-Huei ;

Chouraki, Vincent ;

Ciullo, Marina ;

Coresh, Josef ;

Cornelis, Marilyn C. ;

Curhan, Gary C. ;

d'Adamo, Adamo Pio ;

Dehghan, Abbas ;

Dengler, Laura ;

Ding, Jingzhong ;

Eiriksdottir, Gudny ;

Endlich, Karlhans ;

Enroth, Stefan ;

Esko, Tonu ;

Franco, Oscar H. ;

Gasparini, Paolo ;

Gieger, Christian ;

Girotto, Giorgia ;

Gottesman, Omri ;

Gudnason, Vilmundur ;

Gyllensten, Ulf ;

Hancock, Stephen J. ;

Harris, Tamara B. ;

Helmer, Catherine ;

Hoellerer, Simon ;

Hofer, Edith ;

Hofman, Albert ;

Holliday, Elizabeth G. ;

Homuth, Georg .

SCIENTIFIC REPORTS, 2017, 7

← 1 2 3 4 5 →