Common Variants in Mendelian Kidney Disease Genes and Their Association with Renal Function
Authors: 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, Åsa 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
Journal: Journal of the American Society of Nephrology (2013)

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.