Li, Man and Li, Yong and Weeks, Olivia and Mijatovic, Vladan and Teumer, Alexander and Huffman, Jennifer E. and Tromp, Gerard and Fuchsberger, Christian and Gorski, Mathias and Lyytikainen, Leo-Pekka and Nutile, Teresa and Sedaghat, Sanaz and Sorice, Rossella and Tin, Adrienne and Yang, Qiong and Ahluwalia, Tarunveer S. and Arking, Dan E. and Bihlmeyer, Nathan A. and Boeger, Carsten A. and Carroll, Robert J. and Chasman, Daniel I. and Comelis, Marilyn C. and Dehghan, Abbas and Faul, Jessica D. and Feitosa, Mary F. and Gambaro, Giovanni and Gasparini, Paolo and Giulianini, Franco and Heid, Iris and Huang, Jinyan and Imboden, Medea and Jackson, Anne U. and Jeff, Janina and Jhun, Min A. and Katz, Ronit and Kifley, Annette and Kilpelainen, Tuomas and Kumar, Ashish and Laakso, Markku and Li-Gao, Ruifang and Lohman, Kurt and Lu, Yingchang and Maegi, Reedik and Malerba, Giovanni and Mihailov, Evelin and Mohlke, Karen L. and Mook-Kanamori, Dennis O. and Robino, Antonietta and Ruderfer, Douglas and Salvi, Erika and Schick, Ursula M. and Schulz, Christina-Alexandra and Smith, Albert V. and Smith, Jennifer A. and Traglia, Michela and Yerges-Armstrong, Laura M. and Zhao, Wei and Goodarzi, Mark O. and Kraja, Aldi T. and Liu, Chunyu and Wessel, Jennifer and Boerwinkle, Eric and Borecki, Ingrid B. and Bork-Jensen, Jette and Bottinger, Erwin P. and Braga, Daniele and Brandslund, Ivan and Brody, Jennifer A. and Campbell, Archie and Carey, David J. and Christensen, Cramer and Coresh, Josef and Crook, Errol and Curhan, Gary C. and Cusi, Daniele and de Boer, Ian H. and de Vries, Aiko P. J. and Denny, Joshua C. and Devuyst, Olivier and Dreisbach, Albert W. and Endlich, Karlhans and Esko, Tonu and Franco, Oscar H. and Fulop, Tibor and Gerhard, Glenn S. and Gluemer, Charlotte and Gottesman, Omri and Grarup, Niels and Gudnason, Vilmundur and Hansen, Torben and Harris, Tamara B. and Hayward, Caroline and Hocking, Lynne and Hofman, Albert and Hu, Frank B. and Husemoen, Lise Lotte N. and Jackson, Rebecca D. and Jorgensen, Torben and Jorgensen, Marit E. and Kaehoenen, Mika and Kardia, Sharon L. R. and Koenig, Wolfgang and Kooperberg, Charles and Kriebel, Jennifer and Launer, Lenore J. and Lauritzen, Torsten and Lehtimaki, Terho and Levy, Daniel and Linksted, Pamela and Linneberg, Allan and Liu, Yongmei and Loos, Ruth J. F. and Lupo, Antonio and Meisinger, Christine and Melander, Olle and Metspalu, Andres and Mitchell, Paul and Nauck, Matthias and Nuernberg, Peter and Orho-Melander, Marju and Parsa, Afshin and Pedersen, Oluf and Peters, Annette and Peters, Ulrike and Polasek, Ozren and Porteous, David and Probst-Hensch, Nicole M. and Psaty, Bruce M. and Qi, Lu and Raitakari, Olli T. and Reiner, Alex P. and Rettig, Rainer and Ridker, Paul M. and Rivadeneira, Fernando and Rossouw, Jacques E. and Schmidt, Frank and Siscovick, David and Soranzo, Nicole and Strauch, Konstantin and Toniolo, Daniela and Turner, Stephen T. and Uitterlinden, Andre G. and Ulivi, Sheila and Velayutham, Dinesh and Voelker, Uwe and Volzke, Henry and Waldenberger, Melanie and Wang, Jie Jin and Weir, David R. and Witte, Daniel and Kuivaniemi, Helena and Fox, Caroline S. and Franceschini, Nora and Goessling, Wolfram and Koettgen, Anna and Chu, Audrey Y. (2017) SOS2 and ACP1 Loci Identified through Large-Scale Exome Chip Analysis Regulate Kidney Development and Function. JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 28 (3). pp. 981-994. ISSN 1046-6673, 1533-3450
Full text not available from this repository. (Request a copy)Abstract
Genome-wide association studies have identified >50 common variants associated with kidney function, but these variants do not fully explain the variation in eGFR. We performed a two-stage meta-analysis of associations between genotypes from the Illumina exome array and eGFR on the basis of serum creatinine (eGFRcrea) among participants of European ancestry from the CKDGen Consortium (n(stage1);111,666;n(stage2): 48,343). In single-variant analyses, we identified single nucleotide polymorphisms at seven new loci associated with eGFRcrea (PPM1J, EDEM3, ACP1, SPEG, EYA4, CYP1A1, and ATXN2L; P-stage1<3.7 x10(-7)), of which most were common and annotated as nonsynonymous variants. Gene-based analysis identified associations of functional rare variants in three genes with eGFRcrea, including a novel association with the SOS Ras/Rho guanine nucleotide exchange factor 2 gene, SOS2 (P=5.4x 10(-8) by sequence kernel association test). Experimental follow-up in zebrafish embryos revealed changes in glomerular gene expression and renal tubule morphology in the embryonic kidney of acp1- and sos2-knockdowns. These developmental abnormalities associated with altered blood clearance rate and heightened prevalence of edema. This study expands the number of loci associated with kidney function and identifies novel genes with potential roles in kidney formation.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | LOW-FREQUENCY; NOONAN SYNDROME; RARE VARIANTS; SEQUENCE VARIANTS; DISEASE; ASSOCIATION; METAANALYSIS; COMMON; TRAITS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Nephrologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 13:01 |
| Last Modified: | 26 Feb 2019 12:20 |
| URI: | https://pred.uni-regensburg.de/id/eprint/339 |
Actions (login required)
 |
View Item |
