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

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.

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Item Permalink: https://hdl.handle.net/21.11116/0000-000B-4463-9 Version Permalink: https://hdl.handle.net/21.11116/0000-000C-0852-F

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https://www.ncbi.nlm.nih.gov/pubmed/30367059 (Any fulltext) Open Access status unknown

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Teumer, A., Author
Chaker, L., Author
Groeneweg, S., Author
Li, Y., Author
Di Munno, C., Author
Barbieri, C., Author
Schultheiss, U. T., Author
Traglia, M., Author
Ahluwalia, T. S., Author
Akiyama, M., Author
Appel, E. V. R., Author
Arking, D. E., Author
Arnold, A., Author
Astrup, A., Author
Beekman, M., Author
Beilby, J. P., Author
Bekaert, S., Author
Boerwinkle, E., Author
Brown, S. J., Author
De Buyzere, M., Author
Campbell, P. J., AuthorCeresini, G., AuthorCerqueira, C., AuthorCucca, F., AuthorDeary, I. J., AuthorDeelen, J.¹, Author Eckardt, K. U., AuthorEkici, A. B., AuthorEriksson, J. G., AuthorFerrrucci, L., AuthorFiers, T., AuthorFiorillo, E., AuthorFord, I., AuthorFox, C. S., AuthorFuchsberger, C., AuthorGalesloot, T. E., AuthorGieger, C., AuthorGogele, M., AuthorDe Grandi, A., AuthorGrarup, N., AuthorGreiser, K. H., AuthorHaljas, K., AuthorHansen, T., AuthorHarris, S. E., Authorvan Heemst, D., Authorden Heijer, M., AuthorHicks, A. A., Authorden Hollander, W., AuthorHomuth, G., AuthorHui, J., AuthorIkram, M. A., AuthorIttermann, T., AuthorJensen, R. A., AuthorJing, J., AuthorJukema, J. W., AuthorKajantie, E., AuthorKamatani, Y., AuthorKasbohm, E., AuthorKaufman, J. M., AuthorKiemeney, L. A., AuthorKloppenburg, M., AuthorKronenberg, F., AuthorKubo, M., AuthorLahti, J., AuthorLapauw, B., AuthorLi, S., AuthorLiewald, D. C. M., AuthorLifelines Cohort, Study, AuthorLim, E. M., AuthorLinneberg, A., AuthorMarina, M., AuthorMascalzoni, D., AuthorMatsuda, K., AuthorMedenwald, D., AuthorMeisinger, C., AuthorMeulenbelt, I., AuthorDe Meyer, T., AuthorMeyer Zu Schwabedissen, H. E., AuthorMikolajczyk, R., AuthorMoed, M., AuthorNetea-Maier, R. T., AuthorNolte, I. M., AuthorOkada, Y., AuthorPala, M., AuthorPattaro, C., AuthorPedersen, O., AuthorPetersmann, A., AuthorPorcu, E., AuthorPostmus, I., AuthorPramstaller, P. P., AuthorPsaty, B. M., AuthorRamos, Y. F. M., AuthorRawal, R., AuthorRedmond, P., AuthorRichards, J. B., AuthorRietzschel, E. R., AuthorRivadeneira, F., AuthorRoef, G., AuthorRotter, J. I., AuthorSala, C. F., AuthorSchlessinger, D., AuthorSelvin, E., AuthorSlagboom, P. E., Author Soranzo, N., AuthorSorensen, T. I. A., AuthorSpector, T. D., AuthorStarr, J. M., AuthorStott, D. J., AuthorTaes, Y., AuthorTaliun, D., AuthorTanaka, T., AuthorThuesen, B., AuthorTiller, D., AuthorToniolo, D., AuthorUitterlinden, A. G., AuthorVisser, W. E., AuthorWalsh, J. P., AuthorWilson, S. G., AuthorWolffenbuttel, B. H. R., AuthorYang, Q., AuthorZheng, H. F., AuthorCappola, A., AuthorPeeters, R. P., AuthorNaitza, S., AuthorVolzke, H., AuthorSanna, S., AuthorKottgen, A., AuthorVisser, T. J., AuthorMedici, M., Author more..

Affiliations:
1Deelen – Genetics and Biomarkers of Human Ageing, Research Groups, Max Planck Institute for Biology of Ageing, Max Planck Society, ou_3394006

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Free keywords: 2-Aminoadipate Transaminase/genetics/*metabolism Animals Biological Transport COS Cells Chlorocebus aethiops European Continental Ancestry Group Gene Expression Regulation/*genetics Genome-Wide Association Study Humans Hyperthyroidism/genetics/physiopathology Hypothyroidism/genetics/physiopathology Polymorphism, Single Nucleotide Risk Factors Sodium-Phosphate Cotransporter Proteins, Type I/genetics/*metabolism Thyroid Gland/metabolism/physiopathology Thyroid Hormones/*genetics/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.

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Dates: Published Online: 2018-10-26Date issued: 2018-10-28

Publication Status: Issued

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Identifiers: Other: 30367059
DOI: 10.1038/s41467-018-06356-1
ISSN: 2041-1723 (Electronic)2041-1723 (Linking)

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Title: Nat Commun

Source Genre: Journal

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Pages: - Volume / Issue: 9 (1) Sequence Number: - Start / End Page: 4455 Identifier: -