Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-10-26

AUTHORS

Alexander Teumer, Layal Chaker, Stefan Groeneweg, Yong Li, Celia Di Munno, Caterina Barbieri, Ulla T. Schultheiss, Michela Traglia, Tarunveer S. Ahluwalia, Masato Akiyama, Emil Vincent R. Appel, Dan E. Arking, Alice Arnold, Arne Astrup, Marian Beekman, John P. Beilby, Sofie Bekaert, Eric Boerwinkle, Suzanne J. Brown, Marc De Buyzere, Purdey J. Campbell, Graziano Ceresini, Charlotte Cerqueira, Francesco Cucca, Ian J. Deary, Joris Deelen, Kai-Uwe Eckardt, Arif B. Ekici, Johan G. Eriksson, Luigi Ferrrucci, Tom Fiers, Edoardo Fiorillo, Ian Ford, Caroline S. Fox, Christian Fuchsberger, Tessel E. Galesloot, Christian Gieger, Martin Gögele, Alessandro De Grandi, Niels Grarup, Karin Halina Greiser, Kadri Haljas, Torben Hansen, Sarah E. Harris, Diana van Heemst, Martin den Heijer, Andrew A. Hicks, Wouter den Hollander, Georg Homuth, Jennie Hui, M. Arfan Ikram, Till Ittermann, Richard A. Jensen, Jiaojiao Jing, J. Wouter Jukema, Eero Kajantie, Yoichiro Kamatani, Elisa Kasbohm, Jean-Marc Kaufman, Lambertus A. Kiemeney, Margreet Kloppenburg, Florian Kronenberg, Michiaki Kubo, Jari Lahti, Bruno Lapauw, Shuo Li, David C. M. Liewald, Ee Mun Lim, Allan Linneberg, Michela Marina, Deborah Mascalzoni, Koichi Matsuda, Daniel Medenwald, Christa Meisinger, Ingrid Meulenbelt, Tim De Meyer, Henriette E. Meyer zu Schwabedissen, Rafael Mikolajczyk, Matthijs Moed, Romana T. Netea-Maier, Ilja M. Nolte, Yukinori Okada, Mauro Pala, Cristian Pattaro, Oluf Pedersen, Astrid Petersmann, Eleonora Porcu, Iris Postmus, Peter P. Pramstaller, Bruce M. Psaty, Yolande F. M. Ramos, Rajesh Rawal, Paul Redmond, J. Brent Richards, Ernst R. Rietzschel, Fernando Rivadeneira, Greet Roef, Jerome I. Rotter, Cinzia F. Sala, David Schlessinger, Elizabeth Selvin, P. Eline Slagboom, Nicole Soranzo, Thorkild I. A. Sørensen, Timothy D. Spector, John M. Starr, David J. Stott, Youri Taes, Daniel Taliun, Toshiko Tanaka, Betina Thuesen, Daniel Tiller, Daniela Toniolo, Andre G. Uitterlinden, W. Edward Visser, John P. Walsh, Scott G. Wilson, Bruce H. R. Wolffenbuttel, Qiong Yang, Hou-Feng Zheng, Anne Cappola, Robin P. Peeters, Silvia Naitza, Henry Völzke, Serena Sanna, Anna Köttgen, Theo J. Visser, Marco Medici

ABSTRACT

Thyroid dysfunction is an important public health problem, which affects 10% of the general population and increases the risk of cardiovascular morbidity and mortality. Many aspects of thyroid hormone regulation have only partly been elucidated, including its transport, metabolism, and genetic determinants. Here we report a large meta-analysis of genome-wide association studies for thyroid function and dysfunction, testing 8 million genetic variants in up to 72,167 individuals. One-hundred-and-nine independent genetic variants are associated with these traits. A genetic risk score, calculated to assess their combined effects on clinical end points, shows significant associations with increased risk of both overt (Graves’ disease) and subclinical thyroid disease, as well as clinical complications. By functional follow-up on selected signals, we identify a novel thyroid hormone transporter (SLC17A4) and a metabolizing enzyme (AADAT). Together, these results provide new knowledge about thyroid hormone physiology and disease, opening new possibilities for therapeutic targets. More... »

PAGES

4455

References to SciGraph publications

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  • Journal

    TITLE

    Nature Communications

    ISSUE

    1

    VOLUME

    9

    Author Affiliations

  • DZHK (German Center for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany
  • Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
  • Department of Biometry, Epidemiology and Medical Bioinformatics, Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center—University of Freiburg, Freiburg, Germany
  • Department of Science and Technologies, University of Sannio, Benevento, Italy
  • Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy
  • Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
  • Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
  • McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
  • Department of Biostatistics, University of Washington, Seattle, WA, USA
  • Department of Nutrition, Exercise, and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark
  • Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands
  • School of Biomedical Sciences, University of Western Australia, 6009, Crawley, WA, Australia
  • Bimetra, Clinical Research Center Ghent, Ghent University Hospital, Ghent, Belgium
  • Human Genetics Center, University of Texas Health Science Center, 1200 Pressler Street, 77030, Houston, TX, USA
  • Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, 6009, Nedlands, WA, Australia
  • Department of Cardiology, Ghent University Hospital, Ghent, Belgium
  • Department of Medicine and Surgery, University of Parma, University Hospital of Parma, Parma, Italy
  • Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark
  • Dipartimento di Scienze Biomediche, Università degli Studi di Sassari, Sassari, Italy
  • Department of Psychology, University of Edinburgh, Edinburgh, UK
  • Max Planck Institute for Biology of Ageing, Cologne, Germany
  • Department of Nephrology and Medical Intensive Care, Charité – Universitätsmedizin Berlin, Berlin, Germany
  • Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany
  • National Institute for Health and Welfare, Helsinki, Finland
  • Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA
  • Department of Clinical Chemistry, Ghent University Hospital, Ghent, Belgium
  • Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche Monserrato, Monserrato, Italy
  • Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK
  • Division of Endocrinology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
  • Institute for Biomedicine, Eurac Research, Affiliated Institute of the University of Lubeck, Bolzano, Italy
  • Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands
  • Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Centre for Environmental Health, Neuherberg, Germany
  • German Research Centre Division of Cancer Epidemiology, Heidelberg, Germany
  • Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland
  • Medical Genetics Section, University of Edinburgh Centre for Genomic and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, Edinburgh, UK
  • Leiden University Medical Center, Geriatrics and Gerontology, Leiden, The Netherlands
  • Vrije Universiteit Medisch Centrum, Amsterdam, The Netherlands
  • Department of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
  • Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany
  • Medical School, University of Western Australia, 6009, Crawley, WA, Australia
  • Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
  • Department of Medicine, Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA
  • Faculty of Biology, University of Freiburg, Freiburg, Germany
  • Einthoven Laboratory for Experimental Vascular Medicine, LUMC, Leiden, The Netherlands
  • PEDEGO Research Unit, MRC Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
  • Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
  • Institute of Epidemiology, Friedrich-Loeffler-Institut (FLI), Federal Research Institute for Animal Health, Greifswald, Germany
  • Department of Endocrinology, Ghent University Hospital, Ghent, Belgium
  • Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
  • Department of Medical Genetics, Division of Genetic Epidemiology, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria
  • Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
  • Department of Biostatistics, Boston University, Boston, MA, USA
  • Department of Clinical Experimental Research, Rigshospitalet, Copenhagen, Denmark
  • Department of Computational Biology, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan
  • Institute for Medical Epidemiology, Biostatistics and Informatics, Martin-Luther-University Halle-Wittenberg, Halle, Germany
  • Chair of Epidemiology, Ludwig-Maximilians-Universität München, at UNIKA-T Augsburg, Augsburg, Germany
  • Department of Data Analysis and Mathematical Modelling, Ghent University, Ghent, Belgium
  • Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland
  • Department of Internal Medicine, Division of Endocrinology, Radboud University Medical Center, Nijmegen, The Netherlands
  • Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
  • Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Suita, Japan
  • Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany
  • Center for Integrative Genomics, University of Lausanne, and Swiss Institute of Bioinformatics, 1015, Lausanne, Switzerland
  • Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, Netherlands
  • Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA
  • Helmholtz Zentrum München, Institute of Epidemiology, German Research Center for Environmental Health, Neuherberg, Germany
  • The Department of Twin Research and Genetic Epidemiology, King’s College London, St. Thomas’ Campus, Lambeth Palace Road, SE1 7EH, London, UK
  • Department of Internal Medicine (Cardiology), Ghent University, Ghent, Belgium
  • The Institute for Translational Genomics and Population Sciences, Departments of Pediatrics and Medicine, LABioMed at Harbor-UCLA Medical Center, Torrance, CA, USA
  • Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA
  • Department of Epidemiology, Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
  • The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, CB10 1HH, Cambridge, UK
  • Department of Public Health (Section on Epidemiology), Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
  • Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, UK
  • Institute of Cardiovascular and Medical Sciences, Faculty of Medicine, University of Glasgow, Glasgow, UK
  • AZ Sint Jan Brugge, Brugge, Belgium
  • Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
  • Institute of Aging Research and the Affiliated Hospital, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, China
  • Division of Endocrinology, Diabetes, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
  • Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
  • Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 625 N Wolfe Street, 21205, Baltimore, MD, USA
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-018-06356-1

    DOI

    http://dx.doi.org/10.1038/s41467-018-06356-1

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1107771832

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30367059


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