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

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.; Gogele, 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.; Lifelines Cohort, Study; 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.; Rotter, J. I.; Sala, C. F.; Schlessinger, D.; Selvin, E.; Slagboom, P. E.; Soranzo, N.; Sorensen, T. I. A.; Spector, T. D.; Starr, J. M.; Stott, D. J.; Taes, Y.; 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.; Volzke, H.; Sanna, S.; Kottgen, A.; Visser, T. J.; Medici, M.

doi:10.1038/s41467-018-06356-1

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

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Deelen, J.
Deelen – Genetics and Biomarkers of Human Ageing, Research Groups, Max Planck Institute for Biology of Ageing, Max Planck Society;

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https://www.ncbi.nlm.nih.gov/pubmed/30367059
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Zitation

Teumer, A., Chaker, L., Groeneweg, S., Li, Y., Di Munno, C., Barbieri, C., et al. (2018). Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation. Nat Commun, 9(1), 4455. doi:10.1038/s41467-018-06356-1.

Zitierlink: https://hdl.handle.net/21.11116/0000-000B-4463-9

Zusammenfassung

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.