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

Teumer, A. et al. (2018) Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation. Nature Communications, 9, 4455. (doi:10.1038/s41467-018-06356-1) (PMID:30367059) (PMCID:PMC6203810)

Teumer, A. et al. (2018) Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation. Nature Communications, 9, 4455. (doi:10.1038/s41467-018-06356-1) (PMID:30367059) (PMCID:PMC6203810)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Stott J, Professor David and Ford, Professor Ian
Authors: 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., Gögele, 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., 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., Sørensen, 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., Völzke, H., Sanna, S., Köttgen, A., Visser, T. J., and Medici, M.
Subjects:R Medicine > R Medicine (General)
College/School:College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Nature Communications
Publisher:Nature Publishing Group
ISSN:2041-1723
ISSN (Online):2041-1723
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Nature Communications 9: 4455
Publisher Policy:Reproduced under a Creative Commons License

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