Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation. Issue 1 (December 2018)

• Record Type: Journal Article
• Authors: Teumer, Alexander; Chaker, Layal; Groeneweg, Stefan; Li, Yong; Di Munno, Celia; Barbieri, Caterina; Schultheiss, Ulla; Traglia, Michela; Ahluwalia, Tarunveer; Akiyama, Masato; Appel, Emil; Arking, Dan; Arnold, Alice; Astrup, Arne; Beekman, Marian; Beilby, John; Bekaert, Sofie; Boerwinkle, Eric; Brown, Suzanne; De Buyzere, Marc; Campbell, Purdey; Ceresini, Graziano; Cerqueira, Charlotte; Cucca, Francesco; Deary, Ian; Deelen, Joris; Eckardt, Kai-Uwe; Ekici, Arif; Eriksson, Johan; Ferrrucci, Luigi; Fiers, Tom; Fiorillo, Edoardo; Ford, Ian; Fox, Caroline; Fuchsberger, Christian; Galesloot, Tessel; Gieger, Christian; Gögele, Martin; De Grandi, Alessandro; Grarup, Niels; Greiser, Karin; Haljas, Kadri; Hansen, Torben; Harris, Sarah; Heemst, Diana; Heijer, Martin; Hicks, Andrew; Hollander, Wouter; Homuth, Georg; Hui, Jennie; Ikram, M.; Ittermann, Till; Jensen, Richard; Jing, Jiaojiao; Jukema, J.; Kajantie, Eero; Kamatani, Yoichiro; Kasbohm, Elisa; Kaufman, Jean-Marc; Kiemeney, Lambertus; Kloppenburg, Margreet; Kronenberg, Florian; Kubo, Michiaki; Lahti, Jari; Lapauw, Bruno; Li, Shuo; Liewald, David; Lim, Ee; Linneberg, Allan; Marina, Michela; Mascalzoni, Deborah; Matsuda, Koichi; Medenwald, Daniel; Meisinger, Christa; Meulenbelt, Ingrid; De Meyer, Tim; Meyer zu Schwabedissen, Henriette; Mikolajczyk, Rafael; Moed, Matthijs; Netea-Maier, Romana; Nolte, Ilja; Okada, Yukinori; Pala, Mauro; Pattaro, Cristian; Pedersen, Oluf; Petersmann, Astrid; Porcu, Eleonora; Postmus, Iris; Pramstaller, Peter; Psaty, Bruce; Ramos, Yolande; Rawal, Rajesh; Redmond, Paul; Richards, J.; Rietzschel, Ernst; Rivadeneira, Fernando; Roef, Greet; Rotter, Jerome; Sala, Cinzia; Schlessinger, David; Selvin, Elizabeth; Slagboom, P.; Soranzo, Nicole; Sørensen, Thorkild; Spector, Timothy; Starr, John; Stott, David; Taes, Youri; Taliun, Daniel; Tanaka, Toshiko; Thuesen, Betina; Tiller, Daniel; Toniolo, Daniela; Uitterlinden, Andre; Visser, W.; Walsh, John; Wilson, Scott; Wolffenbuttel, Bruce; Yang, Qiong; Zheng, Hou-Feng; Cappola, Anne; Peeters, Robin; Naitza, Silvia; Völzke, Henry; Sanna, Serena; Köttgen, Anna; Visser, Theo; Medici, Marco;
• Is Part Of: Nature communications. Volume 9:Issue 1(2018)
• Page Start: 1
• Page End: 14
• Publication Date: 2018-12
• Subjects: Biology -- Periodicals; Physical sciences -- Periodicals; 505
• DOI: 10.1038/s41467-018-06356-1
• Languages: English
• ISSNs: 2041-1723

Abstract

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. Thyroid dysfunction is a common public health problem and associated with cardiovascular co-morbidities. Here, the authors carry out genome-wide meta-analysis for thyroid hormone (TH) levels, hyper- and hypothyroidism and identify SLC17A4 as a TH transporter and AADAT as a TH metabolizing enzyme.