1000 Genomes-based meta-analysis identifies 10 novel loci for kidney function View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-12

AUTHORS

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 Borecki, Erwin 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, Åsa 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 WJH 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, Gerard Tromp, Anna Köttgen, Daniela Toniolo, Daniel I. Chasman, Cristian Pattaro, Andre G. Uitterlinden, Albert V. Smith, Jie Jin Wang, Sanaz Sedaghat, Rossella Sorice, Carsten A. Böger, Henry Völzke, Caroline S. Fox, Iris M. Heid, Dragana Vuckovic, Melanie Waldenberger, Qiong Yang, Benedicte Stengel, Jorma S. Viikari, Harold Snieder, Sheila Ulivi, Sylvia Stracke, Konstantin Strauch, Uwe Völker, Peter Vollenweider, Christian Fuchsberger

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 whole-genome sequencing becomes feasible in large samples. More... »

PAGES

45040

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  • Journal

    TITLE

    Scientific Reports

    ISSUE

    1

    VOLUME

    7

    Author Affiliations

  • University Hospital Regensburg
  • University Medical Center Groningen
  • University of Greifswald
  • Brigham and Women's Hospital
  • University of Utah
  • University of Verona
  • University of Trieste
  • European Academy of Bozen
  • Washington University in St. Louis
  • University of Freiburg
  • Loyola University Chicago
  • Johns Hopkins University
  • University of Iceland
  • Hunter Medical Research Institute
  • Institute of Social and Preventive Medicine
  • The University of Texas Health Science Center at Houston
  • Regeneron (United States)
  • Icahn School of Medicine at Mount Sinai
  • National Heart Lung and Blood Institute
  • Istituto Neurologico Mediterraneo
  • Northwestern University
  • Erasmus University Medical Center
  • Wake Forest University
  • Icelandic Heart Association
  • Uppsala University
  • University of Tartu
  • IRCCS Materno Infantile Burlo Garofolo
  • Helmholtz Zentrum München
  • University of Newcastle Australia
  • National Institute on Aging
  • University of Bordeaux
  • University of Regensburg
  • Medical University of Graz
  • German Center for Diabetes Research
  • University of Tampere
  • University of Basel
  • University Hospital Ulm
  • University Medical Centre Mannheim
  • Karolinska Institute
  • Technical University Munich
  • Centre for research in epidemiology and population health
  • University of Sydney
  • German Centre for Cardiovascular Research
  • San Raffaele Hospital
  • University of Turku
  • Harvard University
  • Institute of Genetics and Biophysics
  • Geisinger Medical Center
  • Broad Institute
  • Boston University
  • Ludwig Maximilian University of Munich
  • University Hospital of Lausanne
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/srep45040

    DOI

    http://dx.doi.org/10.1038/srep45040

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1084955756

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/28452372


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