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

Teumer, Alexander and Chaker, Layal and Groeneweg, Stefan and Li, Yong and Di Munno, Celia and Barbieri, Caterina and Schultheiss, Ulla T. and Traglia, Michela and Ahluwalia, Tarunveer S. and Akiyama, Masato and Appel, Emil Vincent R. and Arking, Dan E. and Arnold, Alice and Astrup, Arne and Beekman, Marian and Beilby, John P. and Bekaert, Sofie and Boerwinkle, Eric and Brown, Suzanne J. and De Buyzere, Marc and Campbell, Purdey J. and Ceresini, Graziano and Cerqueira, Charlotte and Cucca, Francesco and Deary, Ian J. and Deelen, Joris and Eckardt, Kai-Uwe and Ekici, Arif B. and Eriksson, Johan G. and Ferrrucci, Luigi and Fiers, Tom and Fiorillo, Edoardo and Ford, Ian and Fox, Caroline S. and Fuchsberger, Christian and Galesloot, Tessel E. and Gieger, Christian and Gögele, Martin and De Grandi, Alessandro and Grarup, Niels and Greiser, Karin Halina and Haljas, Kadri and Hansen, Torben and Harris, Sarah E. and van Heemst, Diana and den Heijer, Martin and Hicks, Andrew A. and den Hollander, Wouter and Homuth, Georg and Hui, Jennie and Ikram, M. Arfan and Ittermann, Till and Jensen, Richard A. and Jing, Jiaojiao and Jukema, J. Wouter and Kajantie, Eero and Kamatani, Yoichiro and Kasbohm, Elisa and Kaufman, Jean-Marc and Kiemeney, Lambertus A. and Kloppenburg, Margreet and Kronenberg, Florian and Kubo, Michiaki and Lahti, Jari and Lapauw, Bruno and Li, Shuo and Liewald, David C. M. and Lifelines Cohort Study, and Lim, Ee Mun and Linneberg, Allan and Marina, Michela and Mascalzoni, Deborah and Matsuda, Koichi and Medenwald, Daniel and Meisinger, Christa and Meulenbelt, Ingrid and De Meyer, Tim and Meyer Zu Schwabedissen, Henriette E. and Mikolajczyk, Rafael and Moed, Matthijs and Netea-Maier, Romana T. and Nolte, Ilja M. and Okada, Yukinori and Pala, Mauro and Pattaro, Cristian and Pedersen, Oluf and Petersmann, Astrid and Porcu, Eleonora and Postmus, Iris and Pramstaller, Peter P. and Psaty, Bruce M. and Ramos, Yolande F. M. and Rawal, Rajesh and Redmond, Paul and Richards, J. Brent and Rietzschel, Ernst R. and Rivadeneira, Fernando and Roef, Greet and Rotter, Jerome I. and Sala, Cinzia F. and Schlessinger, David and Selvin, Elizabeth and Slagboom, P. Eline and Soranzo, Nicole and Sørensen, Thorkild I. A. and Spector, Timothy D. and Starr, John M. and Stott, David J. and Taes, Youri and Taliun, Daniel and Tanaka, Toshiko and Thuesen, Betina and Tiller, Daniel and Toniolo, Daniela and Uitterlinden, Andre G. and Visser, W. Edward and Walsh, John P. and Wilson, Scott G. and Wolffenbuttel, Bruce H. R. and Yang, Qiong and Zheng, Hou-Feng and Cappola, Anne and Peeters, Robin P. and Naitza, Silvia and Völzke, Henry and Sanna, Serena and Köttgen, Anna and Visser, Theo J. and Medici, Marco. (2018) Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation. Nature communications, 9 (1). p. 4455.

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Official URL: https://edoc.unibas.ch/66313/

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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.
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Biopharmazie (Meyer zu Schwabedissen)
UniBasel Contributors:Meyer zu Schwabedissen, Henriette
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:2041-1723
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:26 Apr 2020 19:40
Deposited On:26 Apr 2020 19:40

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