Genome-wide association analyses identify 18 new loci associated with serum urate concentrations View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2013-02

AUTHORS

Anna Köttgen, Eva Albrecht, Alexander Teumer, Veronique Vitart, Jan Krumsiek, Claudia Hundertmark, Giorgio Pistis, Daniela Ruggiero, Conall M O'Seaghdha, Toomas Haller, Qiong Yang, Toshiko Tanaka, Andrew D Johnson, Zoltán Kutalik, Albert V Smith, Julia Shi, Maksim Struchalin, Rita P S Middelberg, Morris J Brown, Angelo L Gaffo, Nicola Pirastu, Guo Li, Caroline Hayward, Tatijana Zemunik, Jennifer Huffman, Loic Yengo, Jing Hua Zhao, Ayse Demirkan, Mary F Feitosa, Xuan Liu, Giovanni Malerba, Lorna M Lopez, Pim van der Harst, Xinzhong Li, Marcus E Kleber, Andrew A Hicks, Ilja M Nolte, Asa Johansson, Federico Murgia, Sarah H Wild, Stephan J L Bakker, John F Peden, Abbas Dehghan, Maristella Steri, Albert Tenesa, Vasiliki Lagou, Perttu Salo, Massimo Mangino, Lynda M Rose, Terho Lehtimäki, Owen M Woodward, Yukinori Okada, Adrienne Tin, Christian Müller, Christopher Oldmeadow, Margus Putku, Darina Czamara, Peter Kraft, Laura Frogheri, Gian Andri Thun, Anne Grotevendt, Gauti Kjartan Gislason, Tamara B Harris, Lenore J Launer, Patrick McArdle, Alan R Shuldiner, Eric Boerwinkle, Josef Coresh, Helena Schmidt, Michael Schallert, Nicholas G Martin, Grant W Montgomery, Michiaki Kubo, Yusuke Nakamura, Toshihiro Tanaka, Patricia B Munroe, Nilesh J Samani, David R Jacobs, Kiang Liu, Pio D'Adamo, Sheila Ulivi, Jerome I Rotter, Bruce M Psaty, Peter Vollenweider, Gerard Waeber, Susan Campbell, Olivier Devuyst, Pau Navarro, Ivana Kolcic, Nicholas Hastie, Beverley Balkau, Philippe Froguel, Tõnu Esko, Andres Salumets, Kay Tee Khaw, Claudia Langenberg, Nicholas J Wareham, Aaron Isaacs, Aldi Kraja, Qunyuan Zhang, Philipp S Wild, Rodney J Scott, Elizabeth G Holliday, Elin Org, Margus Viigimaa, Stefania Bandinelli, Jeffrey E Metter, Antonio Lupo, Elisabetta Trabetti, Rossella Sorice, Angela Döring, Eva Lattka, Konstantin Strauch, Fabian Theis, Melanie Waldenberger, H-Erich Wichmann, Gail Davies, Alan J Gow, Marcel Bruinenberg, LifeLines Cohort Study, Ronald P Stolk, Jaspal S Kooner, Weihua Zhang, Bernhard R Winkelmann, Bernhard O Boehm, Susanne Lucae, Brenda W Penninx, Johannes H Smit, Gary Curhan, Poorva Mudgal, Robert M Plenge, Laura Portas, Ivana Persico, Mirna Kirin, James F Wilson, Irene Mateo Leach, Wiek H van Gilst, Anuj Goel, Halit Ongen, Albert Hofman, Fernando Rivadeneira, Andre G Uitterlinden, Medea Imboden, Arnold von Eckardstein, Francesco Cucca, Ramaiah Nagaraja, Maria Grazia Piras, Matthias Nauck, Claudia Schurmann, Kathrin Budde, Florian Ernst, Susan M Farrington, Evropi Theodoratou, Inga Prokopenko, Michael Stumvoll, Antti Jula, Markus Perola, Veikko Salomaa, So-Youn Shin, Tim D Spector, Cinzia Sala, Paul M Ridker, Mika Kähönen, Jorma Viikari, Christian Hengstenberg, Christopher P Nelson, CAIoGRAM Consortium, DIAGRAM Consortium, ICBP Consortium, MAGIC Consortium, James F Meschia, Michael A Nalls, Pankaj Sharma, Andrew B Singleton, Naoyuki Kamatani, Tanja Zeller, Michel Burnier, John Attia, Maris Laan, Norman Klopp, Hans L Hillege, Stefan Kloiber, Hyon Choi, Mario Pirastu, Silvia Tore, Nicole M Probst-Hensch, Henry Völzke, Vilmundur Gudnason, Afshin Parsa, Reinhold Schmidt, John B Whitfield, Myriam Fornage, Paolo Gasparini, David S Siscovick, Ozren Polašek, Harry Campbell, Igor Rudan, Nabila Bouatia-Naji, Andres Metspalu, Ruth J F Loos, Cornelia M van Duijn, Ingrid B Borecki, Luigi Ferrucci, Giovanni Gambaro, Ian J Deary, Bruce H R Wolffenbuttel, John C Chambers, Winfried März, Peter P Pramstaller, Harold Snieder, Ulf Gyllensten, Alan F Wright, Gerjan Navis, Hugh Watkins, Jacqueline C M Witteman, Serena Sanna, Sabine Schipf, Malcolm G Dunlop, Anke Tönjes, Samuli Ripatti, Nicole Soranzo, Daniela Toniolo, Daniel I Chasman, Olli Raitakari, W H Linda Kao, Marina Ciullo, Caroline S Fox, Mark Caulfield, Murielle Bochud, Christian Gieger

ABSTRACT

Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SFMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout. More... »

PAGES

145

Journal

TITLE

Nature Genetics

ISSUE

2

VOLUME

45

Author Affiliations

  • Johns Hopkins University
  • University of Greifswald
  • University of Edinburgh
  • University Medical Center Freiburg
  • San Raffaele Hospital
  • National Research Council
  • Massachusetts General Hospital
  • University of Tartu
  • Boston University
  • National Institute on Aging
  • National Heart Lung and Blood Institute
  • Swiss Institute of Bioinformatics
  • University of Iceland
  • University of Maryland, Baltimore
  • Erasmus University Medical Center
  • QIMR Berghofer Medical Research Institute
  • University of Cambridge
  • University of Alabama at Birmingham
  • University of Trieste
  • University of Washington
  • University of Split
  • Lille 1 University
  • Washington University in St. Louis
  • University of Verona
  • Imperial College London
  • Heidelberg University
  • European Academy of Bozen
  • Uppsala University
  • Wellcome Centre for Human Genetics
  • Netherlands Consortium for Healthy Ageing
  • Institute of Genetic and Biomedical Research
  • National Institute for Health and Welfare
  • King's College London
  • Brigham and Women's Hospital
  • Tampere University Hospital
  • University of Tokyo
  • University Medical Center Hamburg-Eppendorf
  • University of Newcastle Australia
  • Max Planck Institute of Psychiatry
  • Harvard University
  • University of Basel
  • Icelandic Heart Association
  • The University of Texas Health Science Center at Houston
  • Medical University of Graz
  • RIKEN
  • Queen Mary University of London
  • University of Leicester
  • University of Minnesota
  • Northwestern University
  • Cedars-Sinai Medical Center
  • University Hospital of Lausanne
  • University of Zurich
  • University of Paris-Sud
  • Addenbrooke's Hospital
  • North Estonia Medical Centre
  • Azienda Sanitaria di Firenze
  • Helmholtz Zentrum München
  • Ludwig Maximilian University of Munich
  • Klinikum der Universität München
  • Ealing Hospital
  • University Hospital Ulm
  • Leiden University Medical Center
  • EMGO Institute for Health and Care Research
  • Broad Institute
  • University Hospital of Zurich
  • Leipzig University
  • University of Helsinki
  • Wellcome Sanger Institute
  • Turku University Hospital
  • University Hospital Regensburg
  • Mayo Clinic
  • National Institutes of Health
  • Boston University School of Medicine
  • Pasteur Institute of Lille
  • Catholic University of the Sacred Heart
  • Istituto di Genetica Molecolare
  • Boston Children's Hospital
  • University of Lausanne
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.2500

    DOI

    http://dx.doi.org/10.1038/ng.2500

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1021326074

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/23263486


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