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

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.; Dieffenbach, A.K.; Shuldiner, A.R.; Smith, A.V.; Zappa, A.M.; Lupo, A.; Kollerits, B.; Ponte, B.; Stengel, B.; Krämer, B.K.; Paulweber, B.; Mitchell, B.D.; Hayward, C.; Helmer, C.; Meisinger, C.; Gieger, C.; Shaffer, C.M.; Müller, C.; Langenberg, C.; Ackermann, D.; Siscovick, D.; Boerwinkle, E.; Boerwinkle, E.; Kronenberg, F.; Ehret, G.B.; Homuth, G.; Waeber, G.; Navis, G.; Gambaro, G.; Malerba, G.; Eiriksdottir, G.; Li, G.; Wichmann, H.E.; Grallert, H.; Wallaschofski, H.; Völzke, H.; Brenner, H.; Kramer, H.; Mateo Leach, I.; Rudan, I.; Hillege, H.L.; Beckmann, J.S.; Lambert, J.C.; Luan, J.; Zhao, J.H.; Chalmers, J.; Coresh, J.; Denny, J.C.; Butterbach, K.; Launer, L.J.; Ferrucci, L.; Kedenko, L.; Haun, M.; Metzger, M.; Woodward, M.; Hoffman, M.J.; Nauck, M.; Waldenberger, M.; Pruijm, M.; Bochud, M.; Rheinberger, M.; Verweij, N.; Wareham, N.J.; Endlich, N.; Soranzo, N.; Polasek, O.; van der Harst, P.; Pramstaller, P.P.; Vollenweider, P.; Wild, P.S.; Gansevoort, R.T.; Rettig, R.; Biffar, R.; Carroll, R.J.; Katz, R.; Loos, R.J.; Hwang, S.J.; Coassin, S.; Bergmann, S.; Rosas, S.E.; Stracke, S.; Harris, T.B.; Corre, T.; Zeller, T.; Illig, T.; Aspelund, T.; Tanaka, T.; Lendeckel, U.; Völker, U.; Gudnason, V.; Chouraki, V.; Koenig, W.; Kutalik, Z.; O'Connell, J.R.; Parsa, A.; Heid, I.M.; Paterson, A.D.; de Boer, I.H.; Devuyst, O.; Lazar, J.; Endlich, K.; Susztak, K.; Tremblay, J.; Hamet, P.; Jacob, H.J.; Böger, C.A.; Fox, C.S.; Pattaro, C.; Köttgen, A.

doi:10.2337/db15-1313

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

Details

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Serval ID

serval:BIB_F3223C4A8D96

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

Title

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

Journal

Diabetes

Author(s)

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., Dieffenbach A.K., Shuldiner A.R., Smith A.V., Zappa A.M., Lupo A., Kollerits B., Ponte B., Stengel B., Krämer B.K., Paulweber B., Mitchell B.D., Hayward C., Helmer C., Meisinger C., Gieger C., Shaffer C.M., Müller C., Langenberg C., Ackermann D., Siscovick D., Boerwinkle E., Boerwinkle E., Kronenberg F., Ehret G.B., Homuth G., Waeber G., Navis G., Gambaro G., Malerba G., Eiriksdottir G., Li G., Wichmann H.E., Grallert H., Wallaschofski H., Völzke H., Brenner H., Kramer H., Mateo Leach I., Rudan I., Hillege H.L., Beckmann J.S., Lambert J.C., Luan J., Zhao J.H., Chalmers J., Coresh J., Denny J.C., Butterbach K., Launer L.J., Ferrucci L., Kedenko L., Haun M., Metzger M., Woodward M., Hoffman M.J., Nauck M., Waldenberger M., Pruijm M., Bochud M., Rheinberger M., Verweij N., Wareham N.J., Endlich N., Soranzo N., Polasek O., van der Harst P., Pramstaller P.P., Vollenweider P., Wild P.S., Gansevoort R.T., Rettig R., Biffar R., Carroll R.J., Katz R., Loos R.J., Hwang S.J., Coassin S., Bergmann S., Rosas S.E., Stracke S., Harris T.B., Corre T., Zeller T., Illig T., Aspelund T., Tanaka T., Lendeckel U., Völker U., Gudnason V., Chouraki V., Koenig W., Kutalik Z., O'Connell J.R., Parsa A., Heid I.M., Paterson A.D., de Boer I.H., Devuyst O., Lazar J., Endlich K., Susztak K., Tremblay J., Hamet P., Jacob H.J., Böger C.A., Fox C.S., Pattaro C., Köttgen A.

Working group(s)

DCCT/EDIC

ISSN

1939-327X

ISSN-L

0012-1797

Publication state

Published

Issued date

2016

Peer-reviewed

Oui

Volume

Number

Pages

803-817

Language

english

Notes

Publication types: Journal Article Publication Status: ppublish

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.

OAI-PMH

oai:serval.unil.ch:BIB_F3223C4A8D96

DOI

10.2337/db15-1313

Pubmed

26631737

Web of science

000370961000032

Open Access

Yes

Create date

21/12/2015 17:40