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Teumer, A.* ; Chaker, L.* ; Groeneweg, S.* ; Li, Y.* ; Di Munno, C.* ; Barbieri, C.* ; Schultheiss, U.T.* ; Traglia, M.* ; Ahluwalia, T.S.* ; Akiyama, M.* ; Appel, E.V.R.* ; Arking, D.E.* ; Arnold, A.* ; Astrup, A.* ; Beekman, M.* ; Beilby, J.P.* ; Bekaert, S.* ; Boerwinkle, E.* ; Brown, S.J.* ; De Buyzere, M.* ; Campbell, P.J.* ; Ceresini, G.* ; Cerqueira, C.* ; Cucca, F.* ; Deary, I.J.* ; Deelen, J.* ; Eckardt, K.U.* ; Ekici, A.B.* ; Eriksson, J.G.* ; Ferrrucci, L.* ; Fiers, T.* ; Fiorillo, E.* ; Ford, I.* ; Fox, C.S.* ; Fuchsberger, C.* ; Galesloot, T.E.* ; Gieger, C. ; Gögele, M.* ; de Grandi, A.* ; Grarup, N.* ; Greiser, K.H.* ; Haljas, K.* ; Hansen, T.* ; Harris, S.E.* ; van Heemst, D.* ; den Heijer, M.* ; Hicks, A.A.* ; den Hollander, W.* ; Homuth, G.* ; Hui, J.* ; Ikram, M.A.* ; Ittermann, T.* ; Jensen, R.A.* ; Jing, J.* ; Jukema, J.W.* ; Kajantie, E.* ; Kamatani, Y.* ; Kasbohm, E.* ; Kaufman, J.M.* ; Kiemeney, L.A.* ; Kloppenburg, M.* ; Kronenberg, F.* ; Kubo, M.* ; Lahti, J.* ; Lapauw, B.* ; Li, S.* ; Liewald, D.C.M.* ; Lim, E.M.* ; Linneberg, A.* ; Marina, M.* ; Mascalzoni, D.* ; Matsuda, K.* ; Medenwald, D.* ; Meisinger, C. ; Meulenbelt, I.* ; de Meyer, T.* ; Meyer zu Schwabedissen, H.E.* ; Mikolajczyk, R.* ; Moed, M.* ; Netea-Maier, R.T.* ; Nolte, I.M.* ; Okada, Y.* ; Pala, M.* ; Pattaro, C.* ; Pedersen, O.* ; Petersmann, A.* ; Porcu, E.* ; Postmus, I.* ; Pramstaller, P.P.* ; Psaty, B.M.* ; Ramos, Y.F.M.* ; Rawal, R. ; Redmond, P.* ; Richards, J.B.* ; Rietzschel, E.R.* ; Rivadeneira, F.* ; Roef, G.L.* ; Rotter, J.I.* ; Sala, C.F.* ; Schlessinger, D.* ; Selvin, E.* ; Slagboom, P.E.* ; Soranzo, N.* ; Sørensen, T.I.A.* ; Spector, T.D.* ; Starr, J.M.* ; Stott, D.J.* ; Taes, Y.E.* ; Taliun, D.* ; Tanaka, T.* ; Thuesen, B.* ; Tiller, D.* ; Toniolo, D.* ; Uitterlinden, A.G.* ; Visser, W.E.* ; Walsh, J.P.* ; Wilson, S.G.* ; Wolffenbuttel, B.H.R.* ; Yang, Q.* ; Zheng, H.F.* ; Cappola, A.* ; Peeters, R.P.* ; Naitza, S.* ; Völzke, H.* ; Sanna, S.* ; Köttgen, A.* ; Visser, T.J.* ; Medici, M.*

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

Nat. Commun. 9:4455 (2018)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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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Publication type Article: Journal article
Document type Scientific Article
Keywords Participant Data-analysis; Monocarboxylate Transporter-8; Subclinical Hypothyroidism; Atrial-fibrillation; Reference Range; Association; Risk; Identification; Population; Disease
Language
Publication Year 2018
HGF-reported in Year 2018
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 9, Issue: 1, Pages: , Article Number: 4455 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)
POF-Topic(s) 30202 - Environmental Health
Research field(s) Genetics and Epidemiology
PSP Element(s) G-504091-004
G-504000-010
G-504000-006
DOI 10.1038/s41467-018-06356-1
WOS ID WOS:000448414100005
Scopus ID 85055612686
PubMed ID 30367059
Erfassungsdatum 2018-10-31
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