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Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
 
ID 4486880
Author(s) Teumer, Alexander; Chaker, Layal; Groeneweg, Stefan; Li, Yong; Di Munno, Celia; Barbieri, Caterina; Schultheiss, Ulla T.; Traglia, Michela; Ahluwalia, Tarunveer S.; Akiyama, Masato; Appel, Emil Vincent R.; Arking, Dan E.; Arnold, Alice; Astrup, Arne; Beekman, Marian; Beilby, John P.; Bekaert, Sofie; Boerwinkle, Eric; Brown, Suzanne J.; De Buyzere, Marc; Campbell, Purdey J.; Ceresini, Graziano; Cerqueira, Charlotte; Cucca, Francesco; Deary, Ian J.; Deelen, Joris; Eckardt, Kai-Uwe; Ekici, Arif B.; Eriksson, Johan G.; Ferrrucci, Luigi; Fiers, Tom; Fiorillo, Edoardo; Ford, Ian; Fox, Caroline S.; Fuchsberger, Christian; Galesloot, Tessel E.; Gieger, Christian; Gögele, Martin; De Grandi, Alessandro; Grarup, Niels; Greiser, Karin Halina; Haljas, Kadri; Hansen, Torben; Harris, Sarah E.; van Heemst, Diana; den Heijer, Martin; Hicks, Andrew A.; den Hollander, Wouter; Homuth, Georg; Hui, Jennie; Ikram, M. Arfan; Ittermann, Till; Jensen, Richard A.; Jing, Jiaojiao; Jukema, J. Wouter; Kajantie, Eero; Kamatani, Yoichiro; Kasbohm, Elisa; Kaufman, Jean-Marc; Kiemeney, Lambertus A.; Kloppenburg, Margreet; Kronenberg, Florian; Kubo, Michiaki; Lahti, Jari; Lapauw, Bruno; Li, Shuo; Liewald, David C. M.; Lifelines Cohort Study,; Lim, Ee Mun; Linneberg, Allan; Marina, Michela; Mascalzoni, Deborah; Matsuda, Koichi; Medenwald, Daniel; Meisinger, Christa; Meulenbelt, Ingrid; De Meyer, Tim; Meyer Zu Schwabedissen, Henriette E.; Mikolajczyk, Rafael; Moed, Matthijs; Netea-Maier, Romana T.; Nolte, Ilja M.; Okada, Yukinori; Pala, Mauro; Pattaro, Cristian; Pedersen, Oluf; Petersmann, Astrid; Porcu, Eleonora; Postmus, Iris; Pramstaller, Peter P.; Psaty, Bruce M.; Ramos, Yolande F. M.; Rawal, Rajesh; Redmond, Paul; Richards, J. Brent; Rietzschel, Ernst R.; Rivadeneira, Fernando; Roef, Greet; Rotter, Jerome I.; Sala, Cinzia F.; Schlessinger, David; Selvin, Elizabeth; Slagboom, P. Eline; Soranzo, Nicole; Sørensen, Thorkild I. A.; Spector, Timothy D.; Starr, John M.; Stott, David J.; Taes, Youri; Taliun, Daniel; Tanaka, Toshiko; Thuesen, Betina; Tiller, Daniel; Toniolo, Daniela; Uitterlinden, Andre G.; Visser, W. Edward; Walsh, John P.; Wilson, Scott G.; Wolffenbuttel, Bruce H. R.; Yang, Qiong; Zheng, Hou-Feng; Cappola, Anne; Peeters, Robin P.; Naitza, Silvia; Völzke, Henry; Sanna, Serena; Köttgen, Anna; Visser, Theo J.; Medici, Marco
Author(s) at UniBasel Meyer zu Schwabedissen, Henriette
Year 2018
Title Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation
Journal Nature communications
Volume 9
Number 1
Pages / Article-Number 4455
Mesh terms 2-Aminoadipate Transaminase, metabolism; Animals; Biological Transport; COS Cells; Chlorocebus aethiops; European Continental Ancestry Group; Gene Expression Regulation, genetics; Genome-Wide Association Study; Humans; Hyperthyroidism, physiopathology; Hypothyroidism, physiopathology; Polymorphism, Single Nucleotide; Risk Factors; Sodium-Phosphate Cotransporter Proteins, Type I, metabolism; Thyroid Gland, physiopathology; Thyroid Hormones, metabolism; Thyrotropin, metabolism
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.
ISSN/ISBN 2041-1723
edoc-URL https://edoc.unibas.ch/66313/
Full Text on edoc No
Digital Object Identifier DOI 10.1038/s41467-018-06356-1
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/30367059
Document type (ISI) Journal Article
 
   

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