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

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autor(en): 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
Zeitschrift: Nature Communications
Jahr der Veröffentlichung: 2018
Band: 9
Heftnummer: 1
ISSN: 2041-1723


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.


FAU-Autoren / FAU-Herausgeber

Eckardt, Kai-Uwe Prof. Dr. med.
Medizinische Klinik 4 - Nephrologie und Hypertensiologie
Ekici, Arif Bülent Dr. rer. nat.
Humangenetisches Institut


Autor(en) der externen Einrichtung(en)
Albert-Ludwigs-Universität Freiburg
AZ Sint-Jan
Bispebjerg Hospital
Boston University
Deutsches Krebsforschungszentrum (DKFZ)
Erasmus University Medical Center
Erasmus University Medical Center (MC)
Free University Medical Center / VU Medisch Centrum
Harbor–UCLA Medical Center
Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU)
Helsingin yliopisto / University of Helsinki
Hôpital général juif - Jewish General Hospital
Johns Hopkins University
King’s College London
Leiden University
Ludwig-Maximilians-Universität (LMU)
Martin-Luther-Universität Halle-Wittenberg (MLU)
Medizinische Universität Innsbruck
National Institute for Health and Welfare (THL)
National Institute on Aging (NIA)
PathWest Laboratory Medicine WA
Radboud University Nijmegen
Riken / 理研
San Rafaele Scientific Institute
Sir Charles Gairdner Hospital
Steno Diabetes Center
Università degli Studi di Sassari (UNISS)
Universität Basel
Universitätsmedizin Greifswald / Universitätsklinikum Greifswald
Universität zu Lübeck
Université de Lausanne (UNIL)
Universiteit Gent (UGent) / Ghent University
University Hospital Ghent
University of Copenhagen
University of Edinburgh
University of Glasgow
University of Groningen / Rijksuniversiteit Groningen
University of Parma / Università degli Studi di Parma
University of Pennsylvania
University of Texas Health Science Center at Houston (UTHealth)
University of Tokyo
University of Washington
US National Institutes of Health (NIH)
Wellcome Trust Sanger Institute - Genome Research Limited
Westlake Institute of Advanced Study WIAS


Zitierweisen

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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Zuletzt aktualisiert 2018-03-12 um 09:08