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

Teumer A, Chaker L, Groeneweg S, Li Y, Di Munno C, Barbieri C, Schultheiss UT, Traglia M, Ahluwalia TS, Akiyama M, Appel EVR, Arking DE, Arnold A, Astrup A, Beekman M, Beilby JP, Bekaert S, Boerwinkle E, Brown SJ, De Buyzere M, Campbell PJ, Ceresini G, Cerqueira C, Cucca F, Deary IJ, Deelen J, Eckardt KU, Ekici AB, Eriksson JG, Ferrrucci L, Fiers T, Fiorillo E, Ford I, Fox CS, Fuchsberger C, Galesloot TE, Gieger C, Gogele M, De Grandi A, Grarup N, Greiser KH, Haljas K, Hansen T, Harris SE, Van Heemst D, Den Heijer M, Hicks AA, Den Hollander W, Homuth G, Hui J, Ikrarm MA, Ittermann T, Jensen RA, Jing J, Jukema JW, Kajalltie E, Kamatani Y, Kasbohm E, Kaufman JM, Kiemeney LA, Kloppenburg M, Kronenberg F, Kubo M, Lahti J, Lapauw B, Li S, Liewald DCM, Lim EM, Linneberg A, Marina M, Mascalzoni D, Matsuda K, Medenwald D, Meisinger C, Meulenbelt I, De Meyer T, Zu Schwabedissen HEM, Mikolajczyk R, Moed M, Netea-Maier RT, Nolte IM, Okadah Y, Pala M, Pattaro C, Pedersen O, Petersmann A, Porcu E, Postmus I, Pramstaller PP, Psaty BM, Ramos YFM, Rawal R, Redmond P, Richards JB, Rietzschel ER, Rivadeneira F, Roef G, Rotter J, Sala CF, Schlessinger D, Selvin E, Slagboom PE, Soranzo N, Sorensen TIA, Spector TD, Starr JM, Stott DJ, Taes Y, Taliun D, Tanaka T, Thuesen B, Tiller D, Toniolo D, Uitterlinden AG, Visser WE, Walsh JP, Wilson SG, Wolffenbuttel BHR, Yang Q, Zheng HF, Cappola A, Peeters RP, Naitza S, Voelzke H, Sanna S, Koettgen A, Visser TJ, Medici M (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Book Volume: 9

Journal Issue: 1

DOI: 10.1038/s41467-018-06356-1

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.

Authors with CRIS profile

Involved external institutions

Helsingin yliopisto / University of Helsinki Finland (FI) Bispebjerg Hospital Denmark (DK) Riken Institute of Physical and Chemical Research / 理研 Japan (JP) PathWest Laboratory Medicine WA Australia (AU) Universität zu Lübeck Germany (DE) University Hospital Ghent Belgium (BE) Universität Basel Switzerland (CH) University of Parma / Università degli Studi di Parma Italy (IT) University of Copenhagen Denmark (DK) Boston University United States (USA) (US) Leiden University Netherlands (NL) University of Washington United States (USA) (US) University of Texas Health Science Center at Houston (UTHealth) United States (USA) (US) Sir Charles Gairdner Hospital Australia (AU) Johns Hopkins University (JHU) United States (USA) (US) Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich Germany (DE) Radboud University Nijmegen Netherlands (NL) Medizinische Universität Innsbruck Austria (AT) University of Tokyo Japan (JP) Erasmus University Medical Center (MC) Netherlands (NL) Martin-Luther-Universität Halle-Wittenberg (MLU) Germany (DE) Steno Diabetes Center Denmark (DK) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) Albert-Ludwigs-Universität Freiburg Germany (DE) Universitätsmedizin Greifswald / Universitätsklinikum Greifswald Germany (DE) National Institute on Aging (NIA) United States (USA) (US) San Rafaele Scientific Institute Italy (IT) Free University Medical Center / VU Medisch Centrum Netherlands (NL) US National Institutes of Health (NIH) United States (USA) (US) National Institute for Health and Welfare (THL) Finland (FI) University of Edinburgh United Kingdom (GB) King’s College London United Kingdom (GB) Harbor–UCLA Medical Center United States (USA) (US) Universiteit Gent (UGent) / Ghent University Belgium (BE) Ludwig-Maximilians-Universität (LMU) Germany (DE) Hôpital général juif - Jewish General Hospital Canada (CA) University of Groningen / Rijksuniversiteit Groningen Netherlands (NL) Westlake Institute of Advanced Study WIAS China (CN) Wellcome Trust Sanger Institute - Genome Research Limited United Kingdom (GB) Université de Lausanne (UNIL) Switzerland (CH) University of Pennsylvania United States (USA) (US) Università degli Studi di Sassari (UNISS) Italy (IT) AZ Sint-Jan Netherlands (NL) University of Glasgow United Kingdom (GB)

How to cite

APA:

Teumer, A., Chaker, L., Groeneweg, S., Li, Y., Di Munno, C., Barbieri, C.,... Medici, M. (2018). Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation. Nature Communications, 9(1). https://dx.doi.org/10.1038/s41467-018-06356-1

MLA:

Teumer, Alexander, et al. "Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation." Nature Communications 9.1 (2018).

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