Genome-wide association and functional follow-up reveals new loci for kidney function

Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular...

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Veröffentlicht in:	PLoS genetics 2012-03, Vol.8 (3), p.e1002584
Hauptverfasser:	Pattaro, Cristian, Köttgen, Anna, Teumer, Alexander, Garnaas, Maija, Böger, Carsten A, Fuchsberger, Christian, Olden, Matthias, Chen, Ming-Huei, Tin, Adrienne, Taliun, Daniel, Li, Man, Gao, Xiaoyi, Gorski, Mathias, Yang, Qiong, Hundertmark, Claudia, Foster, Meredith C, O'Seaghdha, Conall M, Glazer, Nicole, Isaacs, Aaron, Liu, Ching-Ti, Smith, Albert V, O'Connell, Jeffrey R, Struchalin, Maksim, Tanaka, Toshiko, Li, Guo, Johnson, Andrew D, Gierman, Hinco J, Feitosa, Mary, Hwang, Shih-Jen, Atkinson, Elizabeth J, Lohman, Kurt, Cornelis, Marilyn C, Johansson, Åsa, Tönjes, Anke, Dehghan, Abbas, Chouraki, Vincent, Holliday, Elizabeth G, Sorice, Rossella, Kutalik, Zoltan, Lehtimäki, Terho, Esko, Tõnu, Deshmukh, Harshal, Ulivi, Sheila, Chu, Audrey Y, Murgia, Federico, Trompet, Stella, Imboden, Medea, Kollerits, Barbara, Pistis, Giorgio, Harris, Tamara B, Launer, Lenore J, Aspelund, Thor, Eiriksdottir, Gudny, Mitchell, Braxton D, Boerwinkle, Eric, Schmidt, Helena, Cavalieri, Margherita, Rao, Madhumathi, Hu, Frank B, Demirkan, Ayse, Oostra, Ben A, de Andrade, Mariza, Turner, Stephen T, Ding, Jingzhong, Andrews, Jeanette S, Freedman, Barry I, Koenig, Wolfgang, Illig, Thomas, Döring, Angela, Wichmann, H-Erich, Kolcic, Ivana, Zemunik, Tatijana, Boban, Mladen, Minelli, Cosetta, Wheeler, Heather E, Igl, Wilmar, Zaboli, Ghazal, Wild, Sarah H, Wright, Alan F, Campbell, Harry, Ellinghaus, David, Nöthlings, Ute, Jacobs, Gunnar, Biffar, Reiner, Endlich, Karlhans, Ernst, Florian, Homuth, Georg, Kroemer, Heyo K, Nauck, Matthias, Stracke, Sylvia, Völker, Uwe, Völzke, Henry, Kovacs, Peter, Stumvoll, Michael, Mägi, Reedik, Hofman, Albert, Uitterlinden, Andre G, Rivadeneira, Fernando, Aulchenko, Yurii S, Polasek, Ozren
Format:	Artikel
Sprache:	eng
Schlagworte:	Aged Aging Animals ATPases Associated with Diverse Cellular Activities Biology Black or African American - genetics Caspase 9 - genetics Chronic kidney failure Cyclin-Dependent Kinases - genetics DEAD-box RNA Helicases - genetics Diabetes Disease DNA Helicases - genetics DNA-Binding Proteins Female Follow-Up Studies Gene Knockdown Techniques Genealogy Genetic aspects Genome-Wide Association Study Genomes Genomics Glomerular filtration rate Glomerular Filtration Rate - genetics Grants Health sciences Heart Humans Kidney - physiopathology Kidney diseases Kidney Failure, Chronic - genetics Kidney Failure, Chronic - pathology Male Medical treatment Middle Aged Pathogenesis Phosphoric Diester Hydrolases - genetics Physiological aspects Public health Statistical methods White People - genetics Zebrafish - genetics
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Zusammenfassung:	Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD.
ISSN:	1553-7404 1553-7390 1553-7404
DOI:	10.1371/journal.pgen.1002584