@article{22196,
  keywords = {Adult, Female, Humans, Aged, Male, Middle Aged, Animals, Genetic Predisposition to Disease, Genome-Wide Association Study, Albuminuria/etiology/ genetics, Cathepsin C/genetics, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 2/complications/ genetics, Diabetic Nephropathies/etiology/ genetics, Gene Knockout Techniques, Kidney/metabolism, Kidney Tubules/ metabolism, Polymorphism, Single Nucleotide, Rats, Receptors, Cell Surface/genetics, Sulfotransferases/genetics, rab GTP-Binding Proteins/genetics/metabolism},
  author = {Yang Q. and Koenig W. and Gudnason V. and Harris T. and Kutalik Z. and Bochud M. and Beckmann J. and Kronenberg F. and Stengel B. and Woodward Mark and Fox C. and Katz R. and Li M. and Chen M. and Eiriksdottir G. and Gansevoort R. and Hamet P. and Li Y. and Coresh J. and Gorski M. and Tin A. and Chu A. and Tayo B. and Pattaro C. and Teumer A. and Tremblay J. and Aspelund T. and Launer L. and Smith A. and Mitchell B. and O'Connell J. and Shuldiner A. and de Boer I. and Li G. and Corre T. and Vollenweider P. and Waeber G. and Hwang S. and Olden M. and Grallert H. and Meisinger C. and Kramer B. and Kramer H. and Rosas S. and van der Harst P. and Coassin S. and Haun M. and Kollerits B. and Paulweber B. and Endlich K. and Volker U. and Rettig R. and Chouraki V. and Helmer C. and Lambert J. and Metzger M. and Parsa A. and Heid I. and Kottgen A. and Boger C. and Langenberg C. and Wareham N. and Tanaka T. and Brenner H. and Sorice R. and Yeo N. and Mijatovic V. and Ko Y. and Taliun D. and Luciani A. and Foster M. and Hiraki L. and Fuchsberger C. and Dieffenbach A. and Zappa A. and Lupo A. and Ponte B. and Hayward C. and Gieger C. and Shaffer C. and Muller C. and Ackermann D. and Siscovick D. and Boerwinkle E. and Ehret G. and Homuth G. and Navis G. and Gambaro G. and Malerba G. and Wichmann H. and Wallaschofski H. and Volzke H. and Rudan I. and Luan J. and Zhao J. and Denny J. and Butterbach K. and Ferrucci L. and Kedenko L. and Hoffman M. and Nauck M. and Waldenberger M. and Pruijm M. and Rheinberger M. and Verweij N. and Endlich N. and Soranzo N. and Polasek O. and Pramstaller P. and Wild P. and Biffar R. and Carroll R. and Loos R. and Bergmann S. and Stracke S. and Zeller T. and Illig T. and Lendeckel U. and Paterson A. and Devuyst O. and Lazar J. and Susztak K. and Jacob H. and I. Leach Mateo and Hillege H. and Chalmers J.},
  title = {Genome-wide Association Studies Identify Genetic Loci Associated With Albuminuria in Diabetes},
  abstract = {<p>
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 x 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 x 10(-7)) and 13% for RAB38/CTSC (P = 5.8 x 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.
</p>
},
  year = {2016},
  journal = {DiabetesDiabetesDiabetes},
  volume = {65},
  edition = {2015/12/04},
  number = {3},
  pages = {803-17},
  isbn = {1939-327X (Electronic)<br/>0012-1797 (Linking)},
  note = {Teumer, Alexander<br/>Tin, Adrienne<br/>Sorice, Rossella<br/>Gorski, Mathias<br/>Yeo, Nan Cher<br/>Chu, Audrey Y<br/>Li, Man<br/>Li, Yong<br/>Mijatovic, Vladan<br/>Ko, Yi-An<br/>Taliun, Daniel<br/>Luciani, Alessandro<br/>Chen, Ming-Huei<br/>Yang, Qiong<br/>Foster, Meredith C<br/>Olden, Matthias<br/>Hiraki, Linda T<br/>Tayo, Bamidele O<br/>Fuchsberger, Christian<br/>Dieffenbach, Aida Karina<br/>Shuldiner, Alan R<br/>Smith, Albert V<br/>Zappa, Allison M<br/>Lupo, Antonio<br/>Kollerits, Barbara<br/>Ponte, Belen<br/>Stengel, Benedicte<br/>Kramer, Bernhard K<br/>Paulweber, Bernhard<br/>Mitchell, Braxton D<br/>Hayward, Caroline<br/>Helmer, Catherine<br/>Meisinger, Christa<br/>Gieger, Christian<br/>Shaffer, Christian M<br/>Muller, Christian<br/>Langenberg, Claudia<br/>Ackermann, Daniel<br/>Siscovick, David<br/>DCCT/EDIC<br/>Boerwinkle, Eric<br/>Kronenberg, Florian<br/>Ehret, Georg B<br/>Homuth, Georg<br/>Waeber, Gerard<br/>Navis, Gerjan<br/>Gambaro, Giovanni<br/>Malerba, Giovanni<br/>Eiriksdottir, Gudny<br/>Li, Guo<br/>Wichmann, H Erich<br/>Grallert, Harald<br/>Wallaschofski, Henri<br/>Volzke, Henry<br/>Brenner, Herrmann<br/>Kramer, Holly<br/>Mateo Leach, I<br/>Rudan, Igor<br/>Hillege, Hans L<br/>Beckmann, Jacques S<br/>Lambert, Jean Charles<br/>Luan, Jian'an<br/>Zhao, Jing Hua<br/>Chalmers, John<br/>Coresh, Josef<br/>Denny, Joshua C<br/>Butterbach, Katja<br/>Launer, Lenore J<br/>Ferrucci, Luigi<br/>Kedenko, Lyudmyla<br/>Haun, Margot<br/>Metzger, Marie<br/>Woodward, Mark<br/>Hoffman, Matthew J<br/>Nauck, Matthias<br/>Waldenberger, Melanie<br/>Pruijm, Menno<br/>Bochud, Murielle<br/>Rheinberger, Myriam<br/>Verweij, Niek<br/>Wareham, Nicholas J<br/>Endlich, Nicole<br/>Soranzo, Nicole<br/>Polasek, Ozren<br/>van der Harst, Pim<br/>Pramstaller, Peter Paul<br/>Vollenweider, Peter<br/>Wild, Philipp S<br/>Gansevoort, Ron T<br/>Rettig, Rainer<br/>Biffar, Reiner<br/>Carroll, Robert J<br/>Katz, Ronit<br/>Loos, Ruth J F<br/>Hwang, Shih-Jen<br/>Coassin, Stefan<br/>Bergmann, Sven<br/>Rosas, Sylvia E<br/>Stracke, Sylvia<br/>Harris, Tamara B<br/>Corre, Tanguy<br/>Zeller, Tanja<br/>Illig, Thomas<br/>Aspelund, Thor<br/>Tanaka, Toshiko<br/>Lendeckel, Uwe<br/>Volker, Uwe<br/>Gudnason, Vilmundur<br/>Chouraki, Vincent<br/>Koenig, Wolfgang<br/>Kutalik, Zoltan<br/>O'Connell, Jeffrey R<br/>Parsa, Afshin<br/>Heid, Iris M<br/>Paterson, Andrew D<br/>de Boer, Ian H<br/>Devuyst, Olivier<br/>Lazar, Jozef<br/>Endlich, Karlhans<br/>Susztak, Katalin<br/>Tremblay, Johanne<br/>Hamet, Pavel<br/>Jacob, Howard J<br/>Boger, Carsten A<br/>Fox, Caroline S<br/>Pattaro, Cristian<br/>Kottgen, Anna<br/>2R01-069321/PHS HHS/United States<br/>2R01-LM0-10098/LM/NLM NIH HHS/United States<br/>DK-063491/DK/NIDDK NIH HHS/United States<br/>DK0-87635/DK/NIDDK NIH HHS/United States<br/>HHSN268200625226C/PHS HHS/United States<br/>HHSN268201100005C/PHS HHS/United States<br/>HHSN268201100006C/PHS HHS/United States<br/>HHSN268201100007C/PHS HHS/United 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NIH HHS/United States<br/>N01-HC-95159/HC/NHLBI NIH HHS/United States<br/>N01-HC-95160/HC/NHLBI NIH HHS/United States<br/>N01-HC-95161/HC/NHLBI NIH HHS/United States<br/>N01-HC-95162/HC/NHLBI NIH HHS/United States<br/>N01-HC-95163/HC/NHLBI NIH HHS/United States<br/>N01-HC-95164/HC/NHLBI NIH HHS/United States<br/>N01-HC-95165/HC/NHLBI NIH HHS/United States<br/>N01-HC-95166/HC/NHLBI NIH HHS/United States<br/>N01-HC-95167/HC/NHLBI NIH HHS/United States<br/>N01-HC-95168/HC/NHLBI NIH HHS/United States<br/>N01-HC-95169/HC/NHLBI NIH HHS/United States<br/>N02-HL-6-4278/HL/NHLBI NIH HHS/United States<br/>P30-DK0-72488/DK/NIDDK NIH HHS/United States<br/>R01-AG-18728/AG/NIA NIH HHS/United States<br/>R01-DK0-76077/DK/NIDDK NIH HHS/United States<br/>R01-HL-071205/HL/NHLBI NIH HHS/United States<br/>R01-HL-088119/HL/NHLBI NIH HHS/United States<br/>R01-HL-9367/HL/NHLBI NIH HHS/United States<br/>R01-HL0-86694/HL/NHLBI NIH HHS/United States<br/>R01-HL0-87641/HL/NHLBI NIH HHS/United States<br/>R01-HL0-87652/HL/NHLBI NIH HHS/United States<br/>RC2-GM092318/GM/NIGMS NIH HHS/United States<br/>U01 DK094157/DK/NIDDK NIH HHS/United States<br/>U01 DK094176/DK/NIDDK NIH HHS/United States<br/>U01-GM-074518-04/GM/NIGMS NIH HHS/United States<br/>U01-HG0-04402/HG/NHGRI NIH HHS/United States<br/>U01-HG04603/HG/NHGRI NIH HHS/United States<br/>U01-HL0-72515-06/HL/NHLBI NIH HHS/United States<br/>U01-HL0-80295/HL/NHLBI NIH HHS/United States<br/>U01-HL0-84756/HL/NHLBI NIH HHS/United States<br/>UL1-RR0-25005/RR/NCRR NIH HHS/United States<br/>WT091310/Wellcome Trust/United Kingdom<br/>WT098051/Wellcome Trust/United Kingdom<br/>Cancer Research UK/United Kingdom<br/>Canadian Institutes of Health Research/Canada<br/>Intramural NIH HHS/United States<br/>Medical Research Council/United Kingdom<br/>Research Support, N.I.H., Extramural<br/>Research Support, N.I.H., Intramural<br/>Research Support, Non-U.S. Gov't<br/>Research Support, U.S. Gov't, Non-P.H.S.<br/>United States<br/>Diabetes. 2016 Mar;65(3):803-17. doi: 10.2337/db15-1313. Epub 2015 Dec 2.},
  language = {eng},
}