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Genome-wide Association Studies Identify Genetic Loci Associated With Albuminuria in Diabetes

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Genome-wide Association Studies Identify Genetic Loci Associated With Albuminuria in Diabetes. / Teumer, Alexander; Tin, Adrienne; Sorice, Rossella; Gorski, Mathias; Yeo, Nan Cher; Chu, Audrey Y; Li, Man; Li, Yong; Mijatovic, Vladan; Ko, Yi-An; Taliun, Daniel; Luciani, Alessandro; Chen, Ming-Huei; Yang, Qiong; Foster, Meredith C; Olden, Matthias; Hiraki, Linda T; Tayo, Bamidele O; Fuchsberger, Christian; Dieffenbach, Aida Karina; Shuldiner, Alan R; Smith, Albert V; Zappa, Allison M; Lupo, Antonio; Kollerits, Barbara; Ponte, Belen; Stengel, Bénédicte; Krämer, Bernhard K; Paulweber, Bernhard; Mitchell, Braxton D; Hayward, Caroline; Helmer, Catherine; Meisinger, Christa; Gieger, Christian; Shaffer, Christian M; Müller, Christian; Langenberg, Claudia; Ackermann, Daniel; Siscovick, David; Boerwinkle, Eric; Kronenberg, Florian; Ehret, Georg B; Homuth, Georg; Waeber, Gerard; Navis, Gerjan; Gambaro, Giovanni; Malerba, Giovanni; Eiriksdottir, Gudny; Li, Guo; Wichmann, H Erich; Grallert, Harald; Wallaschofski, Henri; Völzke, Henry; Brenner, Herrmann; Kramer, Holly; Mateo Leach, I; Rudan, Igor; Hillege, Hans L; Beckmann, Jacques S; Lambert, Jean Charles; Luan, Jian'an; Zhao, Jing Hua; Chalmers, John; Coresh, Josef; Denny, Joshua C; Butterbach, Katja; Launer, Lenore J; Ferrucci, Luigi; Kedenko, Lyudmyla; Haun, Margot; Metzger, Marie; Woodward, Mark; Hoffman, Matthew J; Nauck, Matthias; Waldenberger, Melanie; Pruijm, Menno; Bochud, Murielle; Rheinberger, Myriam; Verweij, Niek; Wareham, Nicholas J; Endlich, Nicole; Soranzo, Nicole; Polasek, Ozren; van der Harst, Pim; Pramstaller, Peter Paul; Vollenweider, Peter; Wild, Philipp S; Gansevoort, Ron T; Rettig, Rainer; Biffar, Reiner; Carroll, Robert J; Katz, Ronit; Loos, Ruth J F; Hwang, Shih-Jen; Coassin, Stefan; Bergmann, Sven; Rosas, Sylvia E; Stracke, Sylvia; Harris, Tamara B; Corre, Tanguy; Zeller, Tanja; Illig, Thomas; Aspelund, Thor; Tanaka, Toshiko; Lendeckel, Uwe; Völker, Uwe; Gudnason, Vilmundur; Chouraki, Vincent; Koenig, Wolfgang; Kutalik, Zoltan; O'Connell, Jeffrey R; Parsa, Afshin; Heid, Iris M; Paterson, Andrew D; de Boer, Ian H; Devuyst, Olivier; Lazar, Jozef; Endlich, Karlhans; Susztak, Katalin; Tremblay, Johanne; Hamet, Pavel; Jacob, Howard J; Böger, Carsten A; Fox, Caroline S; Pattaro, Cristian; Köttgen, Anna; DCCT/EDIC.

in: DIABETES, Jahrgang 65, Nr. 3, 03.2016, S. 803-17.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Teumer, A, Tin, A, Sorice, R, Gorski, M, Yeo, NC, Chu, AY, Li, M, Li, Y, Mijatovic, V, Ko, Y-A, Taliun, D, Luciani, A, Chen, M-H, Yang, Q, Foster, MC, Olden, M, Hiraki, LT, Tayo, BO, Fuchsberger, C, Dieffenbach, AK, Shuldiner, AR, Smith, AV, Zappa, AM, Lupo, A, Kollerits, B, Ponte, B, Stengel, B, Krämer, BK, Paulweber, B, Mitchell, BD, Hayward, C, Helmer, C, Meisinger, C, Gieger, C, Shaffer, CM, Müller, C, Langenberg, C, Ackermann, D, Siscovick, D, Boerwinkle, E, Kronenberg, F, Ehret, GB, Homuth, G, Waeber, G, Navis, G, Gambaro, G, Malerba, G, Eiriksdottir, G, Li, G, Wichmann, HE, Grallert, H, Wallaschofski, H, Völzke, H, Brenner, H, Kramer, H, Mateo Leach, I, Rudan, I, Hillege, HL, Beckmann, JS, Lambert, JC, Luan, J, Zhao, JH, Chalmers, J, Coresh, J, Denny, JC, Butterbach, K, Launer, LJ, Ferrucci, L, Kedenko, L, Haun, M, Metzger, M, Woodward, M, Hoffman, MJ, Nauck, M, Waldenberger, M, Pruijm, M, Bochud, M, Rheinberger, M, Verweij, N, Wareham, NJ, Endlich, N, Soranzo, N, Polasek, O, van der Harst, P, Pramstaller, PP, Vollenweider, P, Wild, PS, Gansevoort, RT, Rettig, R, Biffar, R, Carroll, RJ, Katz, R, Loos, RJF, Hwang, S-J, Coassin, S, Bergmann, S, Rosas, SE, Stracke, S, Harris, TB, Corre, T, Zeller, T, Illig, T, Aspelund, T, Tanaka, T, Lendeckel, U, Völker, U, Gudnason, V, Chouraki, V, Koenig, W, Kutalik, Z, O'Connell, JR, Parsa, A, Heid, IM, Paterson, AD, de Boer, IH, Devuyst, O, Lazar, J, Endlich, K, Susztak, K, Tremblay, J, Hamet, P, Jacob, HJ, Böger, CA, Fox, CS, Pattaro, C, Köttgen, A & DCCT/EDIC 2016, 'Genome-wide Association Studies Identify Genetic Loci Associated With Albuminuria in Diabetes', DIABETES, Jg. 65, Nr. 3, S. 803-17. https://doi.org/10.2337/db15-1313

APA

Teumer, A., Tin, A., Sorice, R., Gorski, M., Yeo, N. C., Chu, A. Y., Li, M., Li, Y., Mijatovic, V., Ko, Y-A., Taliun, D., Luciani, A., Chen, M-H., Yang, Q., Foster, M. C., Olden, M., Hiraki, L. T., Tayo, B. O., Fuchsberger, C., ... DCCT/EDIC (2016). Genome-wide Association Studies Identify Genetic Loci Associated With Albuminuria in Diabetes. DIABETES, 65(3), 803-17. https://doi.org/10.2337/db15-1313

Vancouver

Teumer A, Tin A, Sorice R, Gorski M, Yeo NC, Chu AY et al. Genome-wide Association Studies Identify Genetic Loci Associated With Albuminuria in Diabetes. DIABETES. 2016 Mär;65(3):803-17. https://doi.org/10.2337/db15-1313

Bibtex

@article{3f1603b189ec48a0837f916d57fdb8d0,
title = "Genome-wide Association Studies Identify Genetic Loci Associated With Albuminuria in Diabetes",
abstract = "Elevated concentrations of albumin in the urine, albuminuria, are a hallmark of diabetic kidney disease and are associated with an increased risk for end-stage renal disease and cardiovascular events. To gain insight into the pathophysiological mechanisms underlying albuminuria, we conducted meta-analyses of genome-wide association studies and independent replication in up to 5,825 individuals of European ancestry with diabetes and up to 46,061 without diabetes, followed by functional studies. Known associations of variants in CUBN, encoding cubilin, with the urinary albumin-to-creatinine ratio (UACR) were confirmed in the overall sample (P = 2.4 × 10(-10)). Gene-by-diabetes interactions were detected and confirmed for variants in HS6ST1 and near RAB38/CTSC. Single nucleotide polymorphisms at these loci demonstrated a genetic effect on UACR in individuals with but not without diabetes. The change in the average UACR per minor allele was 21% for HS6ST1 (P = 6.3 × 10(-7)) and 13% for RAB38/CTSC (P = 5.8 × 10(-7)). Experiments using streptozotocin-induced diabetic Rab38 knockout and control rats showed higher urinary albumin concentrations and reduced amounts of megalin and cubilin at the proximal tubule cell surface in Rab38 knockout versus control rats. Relative expression of RAB38 was higher in tubuli of patients with diabetic kidney disease compared with control subjects. The loci identified here confirm known pathways and highlight novel pathways influencing albuminuria.",
keywords = "Adult, Aged, Albuminuria/etiology, Animals, Cathepsin C/genetics, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 2/complications, Diabetic Nephropathies/etiology, Female, Gene Knockout Techniques, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Kidney/metabolism, Kidney Tubules/metabolism, Male, Middle Aged, Polymorphism, Single Nucleotide, Rats, Receptors, Cell Surface/genetics, Sulfotransferases/genetics, rab GTP-Binding Proteins/genetics",
author = "Alexander Teumer and Adrienne Tin and Rossella Sorice and Mathias Gorski and Yeo, {Nan Cher} and Chu, {Audrey Y} and Man Li and Yong Li and Vladan Mijatovic and Yi-An Ko and Daniel Taliun and Alessandro Luciani and Ming-Huei Chen and Qiong Yang and Foster, {Meredith C} and Matthias Olden and Hiraki, {Linda T} and Tayo, {Bamidele O} and Christian Fuchsberger and Dieffenbach, {Aida Karina} and Shuldiner, {Alan R} and Smith, {Albert V} and Zappa, {Allison M} and Antonio Lupo and Barbara Kollerits and Belen Ponte and B{\'e}n{\'e}dicte Stengel and Kr{\"a}mer, {Bernhard K} and Bernhard Paulweber and Mitchell, {Braxton D} and Caroline Hayward and Catherine Helmer and Christa Meisinger and Christian Gieger and Shaffer, {Christian M} and Christian M{\"u}ller and Claudia Langenberg and Daniel Ackermann and David Siscovick and Eric Boerwinkle and Florian Kronenberg and Ehret, {Georg B} and Georg Homuth and Gerard Waeber and Gerjan Navis and Giovanni Gambaro and Giovanni Malerba and Gudny Eiriksdottir and Guo Li and Wichmann, {H Erich} and Harald Grallert and Henri Wallaschofski and Henry V{\"o}lzke and Herrmann Brenner and Holly Kramer and {Mateo Leach}, I and Igor Rudan and Hillege, {Hans L} and Beckmann, {Jacques S} and Lambert, {Jean Charles} and Jian'an Luan and Zhao, {Jing Hua} and John Chalmers and Josef Coresh and Denny, {Joshua C} and Katja Butterbach and Launer, {Lenore J} and Luigi Ferrucci and Lyudmyla Kedenko and Margot Haun and Marie Metzger and Mark Woodward and Hoffman, {Matthew J} and Matthias Nauck and Melanie Waldenberger and Menno Pruijm and Murielle Bochud and Myriam Rheinberger and Niek Verweij and Wareham, {Nicholas J} and Nicole Endlich and Nicole Soranzo and Ozren Polasek and {van der Harst}, Pim and Pramstaller, {Peter Paul} and Peter Vollenweider and Wild, {Philipp S} and Gansevoort, {Ron T} and Rainer Rettig and Reiner Biffar and Carroll, {Robert J} and Ronit Katz and Loos, {Ruth J F} and Shih-Jen Hwang and Stefan Coassin and Sven Bergmann and Rosas, {Sylvia E} and Sylvia Stracke and Harris, {Tamara B} and Tanguy Corre and Tanja Zeller and Thomas Illig and Thor Aspelund and Toshiko Tanaka and Uwe Lendeckel and Uwe V{\"o}lker and Vilmundur Gudnason and Vincent Chouraki and Wolfgang Koenig and Zoltan Kutalik and O'Connell, {Jeffrey R} and Afshin Parsa and Heid, {Iris M} and Paterson, {Andrew D} and {de Boer}, {Ian H} and Olivier Devuyst and Jozef Lazar and Karlhans Endlich and Katalin Susztak and Johanne Tremblay and Pavel Hamet and Jacob, {Howard J} and B{\"o}ger, {Carsten A} and Fox, {Caroline S} and Cristian Pattaro and Anna K{\"o}ttgen and DCCT/EDIC",
note = "{\textcopyright} 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.",
year = "2016",
month = mar,
doi = "10.2337/db15-1313",
language = "English",
volume = "65",
pages = "803--17",
journal = "DIABETES",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "3",

}

RIS

TY - JOUR

T1 - Genome-wide Association Studies Identify Genetic Loci Associated With Albuminuria in Diabetes

AU - Teumer, Alexander

AU - Tin, Adrienne

AU - Sorice, Rossella

AU - Gorski, Mathias

AU - Yeo, Nan Cher

AU - Chu, Audrey Y

AU - Li, Man

AU - Li, Yong

AU - Mijatovic, Vladan

AU - Ko, Yi-An

AU - Taliun, Daniel

AU - Luciani, Alessandro

AU - Chen, Ming-Huei

AU - Yang, Qiong

AU - Foster, Meredith C

AU - Olden, Matthias

AU - Hiraki, Linda T

AU - Tayo, Bamidele O

AU - Fuchsberger, Christian

AU - Dieffenbach, Aida Karina

AU - Shuldiner, Alan R

AU - Smith, Albert V

AU - Zappa, Allison M

AU - Lupo, Antonio

AU - Kollerits, Barbara

AU - Ponte, Belen

AU - Stengel, Bénédicte

AU - Krämer, Bernhard K

AU - Paulweber, Bernhard

AU - Mitchell, Braxton D

AU - Hayward, Caroline

AU - Helmer, Catherine

AU - Meisinger, Christa

AU - Gieger, Christian

AU - Shaffer, Christian M

AU - Müller, Christian

AU - Langenberg, Claudia

AU - Ackermann, Daniel

AU - Siscovick, David

AU - Boerwinkle, Eric

AU - Kronenberg, Florian

AU - Ehret, Georg B

AU - Homuth, Georg

AU - Waeber, Gerard

AU - Navis, Gerjan

AU - Gambaro, Giovanni

AU - Malerba, Giovanni

AU - Eiriksdottir, Gudny

AU - Li, Guo

AU - Wichmann, H Erich

AU - Grallert, Harald

AU - Wallaschofski, Henri

AU - Völzke, Henry

AU - Brenner, Herrmann

AU - Kramer, Holly

AU - Mateo Leach, I

AU - Rudan, Igor

AU - Hillege, Hans L

AU - Beckmann, Jacques S

AU - Lambert, Jean Charles

AU - Luan, Jian'an

AU - Zhao, Jing Hua

AU - Chalmers, John

AU - Coresh, Josef

AU - Denny, Joshua C

AU - Butterbach, Katja

AU - Launer, Lenore J

AU - Ferrucci, Luigi

AU - Kedenko, Lyudmyla

AU - Haun, Margot

AU - Metzger, Marie

AU - Woodward, Mark

AU - Hoffman, Matthew J

AU - Nauck, Matthias

AU - Waldenberger, Melanie

AU - Pruijm, Menno

AU - Bochud, Murielle

AU - Rheinberger, Myriam

AU - Verweij, Niek

AU - Wareham, Nicholas J

AU - Endlich, Nicole

AU - Soranzo, Nicole

AU - Polasek, Ozren

AU - van der Harst, Pim

AU - Pramstaller, Peter Paul

AU - Vollenweider, Peter

AU - Wild, Philipp S

AU - Gansevoort, Ron T

AU - Rettig, Rainer

AU - Biffar, Reiner

AU - Carroll, Robert J

AU - Katz, Ronit

AU - Loos, Ruth J F

AU - Hwang, Shih-Jen

AU - Coassin, Stefan

AU - Bergmann, Sven

AU - Rosas, Sylvia E

AU - Stracke, Sylvia

AU - Harris, Tamara B

AU - Corre, Tanguy

AU - Zeller, Tanja

AU - Illig, Thomas

AU - Aspelund, Thor

AU - Tanaka, Toshiko

AU - Lendeckel, Uwe

AU - Völker, Uwe

AU - Gudnason, Vilmundur

AU - Chouraki, Vincent

AU - Koenig, Wolfgang

AU - Kutalik, Zoltan

AU - O'Connell, Jeffrey R

AU - Parsa, Afshin

AU - Heid, Iris M

AU - Paterson, Andrew D

AU - de Boer, Ian H

AU - Devuyst, Olivier

AU - Lazar, Jozef

AU - Endlich, Karlhans

AU - Susztak, Katalin

AU - Tremblay, Johanne

AU - Hamet, Pavel

AU - Jacob, Howard J

AU - Böger, Carsten A

AU - Fox, Caroline S

AU - Pattaro, Cristian

AU - Köttgen, Anna

AU - DCCT/EDIC

N1 - © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

PY - 2016/3

Y1 - 2016/3

N2 - Elevated concentrations of albumin in the urine, albuminuria, are a hallmark of diabetic kidney disease and are associated with an increased risk for end-stage renal disease and cardiovascular events. To gain insight into the pathophysiological mechanisms underlying albuminuria, we conducted meta-analyses of genome-wide association studies and independent replication in up to 5,825 individuals of European ancestry with diabetes and up to 46,061 without diabetes, followed by functional studies. Known associations of variants in CUBN, encoding cubilin, with the urinary albumin-to-creatinine ratio (UACR) were confirmed in the overall sample (P = 2.4 × 10(-10)). Gene-by-diabetes interactions were detected and confirmed for variants in HS6ST1 and near RAB38/CTSC. Single nucleotide polymorphisms at these loci demonstrated a genetic effect on UACR in individuals with but not without diabetes. The change in the average UACR per minor allele was 21% for HS6ST1 (P = 6.3 × 10(-7)) and 13% for RAB38/CTSC (P = 5.8 × 10(-7)). Experiments using streptozotocin-induced diabetic Rab38 knockout and control rats showed higher urinary albumin concentrations and reduced amounts of megalin and cubilin at the proximal tubule cell surface in Rab38 knockout versus control rats. Relative expression of RAB38 was higher in tubuli of patients with diabetic kidney disease compared with control subjects. The loci identified here confirm known pathways and highlight novel pathways influencing albuminuria.

AB - Elevated concentrations of albumin in the urine, albuminuria, are a hallmark of diabetic kidney disease and are associated with an increased risk for end-stage renal disease and cardiovascular events. To gain insight into the pathophysiological mechanisms underlying albuminuria, we conducted meta-analyses of genome-wide association studies and independent replication in up to 5,825 individuals of European ancestry with diabetes and up to 46,061 without diabetes, followed by functional studies. Known associations of variants in CUBN, encoding cubilin, with the urinary albumin-to-creatinine ratio (UACR) were confirmed in the overall sample (P = 2.4 × 10(-10)). Gene-by-diabetes interactions were detected and confirmed for variants in HS6ST1 and near RAB38/CTSC. Single nucleotide polymorphisms at these loci demonstrated a genetic effect on UACR in individuals with but not without diabetes. The change in the average UACR per minor allele was 21% for HS6ST1 (P = 6.3 × 10(-7)) and 13% for RAB38/CTSC (P = 5.8 × 10(-7)). Experiments using streptozotocin-induced diabetic Rab38 knockout and control rats showed higher urinary albumin concentrations and reduced amounts of megalin and cubilin at the proximal tubule cell surface in Rab38 knockout versus control rats. Relative expression of RAB38 was higher in tubuli of patients with diabetic kidney disease compared with control subjects. The loci identified here confirm known pathways and highlight novel pathways influencing albuminuria.

KW - Adult

KW - Aged

KW - Albuminuria/etiology

KW - Animals

KW - Cathepsin C/genetics

KW - Diabetes Mellitus, Experimental

KW - Diabetes Mellitus, Type 2/complications

KW - Diabetic Nephropathies/etiology

KW - Female

KW - Gene Knockout Techniques

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Humans

KW - Kidney/metabolism

KW - Kidney Tubules/metabolism

KW - Male

KW - Middle Aged

KW - Polymorphism, Single Nucleotide

KW - Rats

KW - Receptors, Cell Surface/genetics

KW - Sulfotransferases/genetics

KW - rab GTP-Binding Proteins/genetics

U2 - 10.2337/db15-1313

DO - 10.2337/db15-1313

M3 - SCORING: Journal article

C2 - 26631737

VL - 65

SP - 803

EP - 817

JO - DIABETES

JF - DIABETES

SN - 0012-1797

IS - 3

ER -