Common variants in Mendelian kidney disease genes and their association with renal function.

Authors:
Dr Zoltán Kutalik, PhD
Dr Zoltán Kutalik, PhD
Institute of Social and Preventive Medicine, CHUV
Assistant Professor
Biostatistics
Lausanne, Vaud | Switzerland
Afshin Parsa Christian Fuchsberger Anna Köttgen Conall M O'Seaghdha Cristian Pattaro Mariza de Andrade Daniel I Chasman Alexander Teumer Karlhans Endlich Matthias Olden Ming-Huei Chen Adrienne Tin Young J Kim Daniel Taliun Man Li Mary Feitosa Mathias Gorski Qiong Yang Claudia Hundertmark Meredith C Foster Nicole Glazer Aaron Isaacs Madhumathi Rao Albert V Smith Jeffrey R O'Connell Maksim Struchalin Toshiko Tanaka Guo Li Shih-Jen Hwang Elizabeth J Atkinson Kurt Lohman Marilyn C Cornelis Asa Johansson Anke Tönjes Abbas Dehghan Vincent Couraki 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 Edith Hofer Frank Hu Ayse Demirkan Ben A Oostra Stephen T Turner Jingzhong Ding Jeanette S Andrews Barry I Freedman Franco Giulianini Wolfgang Koenig Thomas Illig Angela Döring H-Erich Wichmann Lina Zgaga 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 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 Bénédicte Stengel Daniela Ruggiero Sven Bergmann Mika Kähönen Jorma Viikari Tiit Nikopensius Michael Province Helen Colhoun Alex Doney Antonietta Robino Bernhard K Krämer Laura Portas Ian Ford Brendan M Buckley Martin Adam Gian-Andri Thun Bernhard Paulweber Margot Haun Cinzia Sala Paul Mitchell Marina Ciullo 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 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 Witteman Caroline Hayward Paul M Ridker Murielle Bochud Iris M Heid David S Siscovick Caroline S Fox W Linda Kao Carsten A Böger

J Am Soc Nephrol 2013 Dec 12;24(12):2105-17. Epub 2013 Sep 12.

Division of Nephrology, University of Maryland School of Medicine, Baltimore, Maryland;

Many common genetic variants identified by genome-wide association studies for complex traits map to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2 meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research.

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http://dx.doi.org/10.1681/ASN.2012100983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3839542PMC
December 2013
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10 Citations
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