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

Authors:
Dr Zoltán Kutalik, PhD
Dr Zoltán Kutalik, PhD
Institute of Social and Preventive Medicine, CHUV
Assistant Professor
Biostatistics
Lausanne, Vaud | Switzerland
Dr. Hinco J Gierman, PhD
Dr. Hinco J Gierman, PhD
illumina
Senior Manager Scientific & Translational Software
CA | United States
Cristian Pattaro Anna Köttgen Alexander Teumer Maija Garnaas Carsten A Böger Christian Fuchsberger Matthias Olden Ming-Huei Chen Adrienne Tin Daniel Taliun Man Li Xiaoyi Gao Mathias Gorski Qiong Yang Claudia Hundertmark Meredith C Foster Conall M O'Seaghdha Nicole Glazer Aaron Isaacs Ching-Ti Liu Albert V Smith Jeffrey R O'Connell Maksim Struchalin Toshiko Tanaka Guo Li Andrew D Johnson Mary Feitosa Shih-Jen Hwang Elizabeth J Atkinson Kurt Lohman Marilyn C Cornelis Åsa Johansson Anke Tönjes Abbas Dehghan Vincent Chouraki Elizabeth G Holliday Rossella Sorice Zoltan Kutalik Terho Lehtimäki Tõnu Esko Harshal Deshmukh Sheila Ulivi Audrey Y Chu Federico Murgia Stella Trompet Medea Imboden Barbara Kollerits Giorgio Pistis Tamara B Harris Lenore J Launer Thor Aspelund Gudny Eiriksdottir Braxton D Mitchell Eric Boerwinkle Helena Schmidt Margherita Cavalieri Madhumathi Rao Frank B Hu Ayse Demirkan Ben A Oostra Mariza de Andrade Stephen T Turner Jingzhong Ding Jeanette S Andrews Barry I Freedman Wolfgang Koenig Thomas Illig Angela Döring H-Erich Wichmann Ivana Kolcic Tatijana Zemunik Mladen Boban Cosetta Minelli Heather E Wheeler Wilmar Igl Ghazal Zaboli Sarah H Wild Alan F Wright Harry Campbell David Ellinghaus Ute Nöthlings Gunnar Jacobs Reiner Biffar Karlhans Endlich Florian Ernst Georg Homuth Heyo K Kroemer Matthias Nauck Sylvia Stracke Uwe Völker Henry Völzke Peter Kovacs Michael Stumvoll Reedik Mägi Albert Hofman Andre G Uitterlinden Fernando Rivadeneira Yurii S Aulchenko Ozren Polasek Nick Hastie Veronique Vitart Catherine Helmer Jie Jin Wang Daniela Ruggiero Sven Bergmann Mika Kähönen Jorma Viikari Tiit Nikopensius Michael Province Shamika Ketkar Helen Colhoun Alex Doney Antonietta Robino Franco Giulianini Bernhard K Krämer Laura Portas Ian Ford Brendan M Buckley Martin Adam Gian-Andri Thun Bernhard Paulweber Margot Haun Cinzia Sala Marie Metzger Paul Mitchell Marina Ciullo Stuart K Kim Peter Vollenweider Olli Raitakari Andres Metspalu Colin Palmer Paolo Gasparini Mario Pirastu J Wouter Jukema Nicole M Probst-Hensch Florian Kronenberg Daniela Toniolo Vilmundur Gudnason Alan R Shuldiner Josef Coresh Reinhold Schmidt Luigi Ferrucci David S Siscovick Cornelia M van Duijn Ingrid Borecki Sharon L R Kardia Yongmei Liu Gary C Curhan Igor Rudan Ulf Gyllensten James F Wilson Andre Franke Peter P Pramstaller Rainer Rettig Inga Prokopenko Jacqueline C M Witteman Caroline Hayward Paul Ridker Afshin Parsa Murielle Bochud Iris M Heid Wolfram Goessling Daniel I Chasman W H Linda Kao Caroline S Fox

PLoS Genet 2012 29;8(3):e1002584. Epub 2012 Mar 29.

Institute of Genetic Medicine, European Academy of Bozen/Bolzano (EURAC) and Affiliated Institute of the University of Lübeck, Bolzano, Italy.

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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http://dx.doi.org/10.1371/journal.pgen.1002584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3315455PMC
September 2012
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