1000 Genomes-based metaanalysis identifies 10 novel loci for kidney function

Mathias Gorski*, Peter J. Van Der Most, Alexander Teumer, Audrey Y. Chu, Man Li, Vladan Mijatovic, Ilja M. Nolte, Massimiliano Cocca, Daniel Taliun, Felicia Gomez, Yong Li, Bamidele Tayo, Adrienne Tin, Mary F. Feitosa, Thor Aspelund, John Attia, Reiner Biffar, Murielle Bochud, Eric Boerwinkle, Ingrid BoreckiErwin P. Bottinger, Ming Huei Chen, Vincent Chouraki, Marina Ciullo, Josef Coresh, Marilyn C. Cornelis, Gary C. Curhan, Adamo Pio D'Adamo, Abbas Dehghan, Laura Dengler, Jingzhong Ding, Gudny Eiriksdottir, Karlhans Endlich, Stefan Enroth, Tõnu Esko, Oscar H. Franco, Paolo Gasparini, Christian Gieger, Giorgia Girotto, Omri Gottesman, Vilmundur Gudnason, Ulf Gyllensten, Stephen J. Hancock, Tamara B. Harris, Catherine Helmer, Simon Höllerer, Edith Hofer, Albert Hofman, Elizabeth G. Holliday, Georg Homuth, Frank B. Hu, Cornelia Huth, Nina Hutri-Kähönen, Shih Jen Hwang, Medea Imboden, Asa Johansson, Mika Kähönen, Wolfgang König, Holly Kramer, Bernhard K. Krämer, Ashish Kumar, Zoltan Kutalik, Jean Charles Lambert, Lenore J. Launer, Terho Lehtimäki, Martin H. De Borst, Gerjan Navis, Morris Swertz, Yongmei Liu, Kurt Lohman, Ruth J.F. Loos, Yingchang Lu, Leo Pekka Lyytikäinen, Mark A. McEvoy, Christa Meisinger, Thomas Meitinger, Andres Metspalu, Marie Metzger, Evelin Mihailov, Paul Mitchell, Matthias Nauck, Albertine J. Oldehinkel, Matthias Olden, Brenda W.J.H. Penninx, Giorgio Pistis, Peter P. Pramstaller, Nicole Probst-Hensch, Olli T. Raitakari, Rainer Rettig, Paul M. Ridker, Fernando Rivadeneira, Antonietta Robino, Sylvia E. Rosas, Douglas Ruderfer, Daniela Ruggiero, Yasaman Saba, Cinzia Sala, Helena Schmidt, Reinhold Schmidt, Rodney J. Scott, Sanaz Sedaghat, Albert V. Smith, Rossella Sorice, Benedicte Stengel, Sylvia Stracke, Konstantin Strauch, Daniela Toniolo, Andre G. Uitterlinden, Sheila Ulivi, Jorma S. Viikari, Uwe Völker, Peter Vollenweider, Henry Völzke, Dragana Vuckovic, Melanie Waldenberger, Jie Jin Wang, Qiong Yang, Daniel I. Chasman, Gerard Tromp, Harold Snieder, Iris M. Heid, Caroline S. Fox, Anna Köttgen, Cristian Pattaro, Carsten A. Böger, Christian Fuchsberger

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

HapMap imputed genome-wide association studies (GWAS) have revealed >50 loci at which common variants with minor allele frequency >5% are associated with kidney function. GWAS using more complete reference sets for imputation, such as those from The 1000 Genomes project, promise to identify novel loci that have been missed by previous efforts. To investigate the value of such a more complete variant catalog, we conducted a GWAS meta-Analysis of kidney function based on the estimated glomerular filtration rate (EGFR) in 110,517 European ancestry participants using 1000 Genomes imputed data. We identified 10 novel loci with p-value < 5 × 10-8 previously missed by HapMap-based GWAS. Six of these loci (HOXD8, ARL15, PIK3R1, EYA4, ASTN2, and EPB41L3) are tagged by common SNPs unique to the 1000 Genomes reference panel. Using pathway analysis, we identified 39 significant (FDR < 0.05) genes and 127 significantly (FDR < 0.05) enriched gene sets, which were missed by our previous analyses. Among those, the 10 identified novel genes are part of pathways of kidney development, carbohydrate metabolism, cardiac septum development and glucose metabolism. These results highlight the utility of re-imputing from denser reference panels, until wholegenome sequencing becomes feasible in large samples.

Original languageEnglish
Article number45040
JournalScientific Reports
Volume7
DOIs
Publication statusPublished - 2017

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