Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation
Authors: 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, Alizadeh Behrooz Z. , Boezen H. Marike , Franke Lude , van der Harst Pim , Navis Gerjan , Rots Marianne , Snieder Harold , Swertz Morris A. , Wijmenga Cisca , 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 
Published: October 2018

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.