A1 Refereed original research article in a scientific journal
Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation
Authors: 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 JN, Ikrarm MA, Ittermann T, Jensen RA, Jing J, Jukema JW, Kajantie 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 JI, 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, Volzke H, Sanna S, Kottgen A, Visser TJ, Medici M
Publisher: NATURE PUBLISHING GROUP
Publication year: 2018
Journal:: Nature Communications
Journal name in source: NATURE COMMUNICATIONS
Journal acronym: NAT COMMUN
Article number: ARTN 4455
Volume: 9
Number of pages: 14
ISSN: 2041-1723
DOI: https://doi.org/10.1038/s41467-018-06356-1
Web address : https://www.nature.com/articles/s41467-018-06356-1
Self-archived copy’s web address: https://research.utu.fi/converis/portal/Publication/39505764
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.
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