Genome-wide association and functional follow-up reveals new loci for kidney function by 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, CARDIoGRAM Consortium, ICBP Consortium, CARe Consortium, Wellcome Trust Case Control Consortium 2 (WTCCC2), 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, Hastie Nick, Vitart Veronique, Helmer Catherine, Wang Jie Jin, Ruggiero Daniela, Bergmann Sven, Kähönen Mika, Viikari Jorma, Nikopensius Tiit, Province Michael, Ketkar Shamika, Colhoun Helen, Doney Alex, Robino Antonietta, Giulianini Franco, Krämer Bernhard K, Portas Laura, Ford Ian, Buckley Brendan M, Adam Martin, Thun Gian-Andri, Paulweber Bernhard, Haun Margot, Sala Cinzia, Metzger Marie, Mitchell Paul, Ciullo Marina, Kim Stuart K, Vollenweider Peter, Raitakari Olli, Metspalu Andres, Palmer Colin, Gasparini Paolo, Pirastu Mario, Jukema J Wouter, Probst-Hensch Nicole M, Kronenberg Florian, Toniolo Daniela, Gudnason Vilmundur, Shuldiner Alan R, Coresh Josef, Schmidt Reinhold, Ferrucci Luigi, Siscovick David S, van Duijn Cornelia M, Borecki Ingrid, Kardia Sharon L R, Liu Yongmei, Curhan Gary C, Rudan Igor, Gyllensten Ulf, Wilson James F, Franke Andre, Pramstaller Peter P, Rettig Rainer, Prokopenko Inga, Witteman Jacqueline C M, Hayward Caroline, Ridker Paul, Parsa Afshin, Bochud Murielle, Heid Iris M, Goessling Wolfram, Chasman Daniel I, Kao W H Linda, Fox Caroline S in PLoS genetics (2012). PubMed

Abstract

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.

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