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Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation.
Wednesday,2019-01-09 13:09 America/Los_Angeles — ecterry
| Title | Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation. |
| Publication Type | Journal Article |
| Year of Publication | 2018 |
| Authors | Teumer, A, Chaker, L, Groeneweg, S, Li, Y, Di Munno, C, Barbieri, C, Schultheiss, UT, Traglia, M, Ahluwalia, TS, Akiyama, M, Appel, EVincent R, Arking, DE, Arnold, A, Astrup, A, Beekman, M, Beilby, JP, Bekaert, S, Boerwinkle, E, Brown, SJ, De Buyzere, M, Campbell, PJ, Ceresini, G, Cerqueira, C, Cucca, F, Deary, IJ, Deelen, J, Eckardt, K-U, Ekici, AB, Eriksson, JG, Ferrrucci, L, Fiers, T, Fiorillo, E, Ford, I, Fox, CS, Fuchsberger, C, Galesloot, TE, Gieger, C, Gögele, M, De Grandi, A, Grarup, N, Greiser, KHalina, Haljas, K, Hansen, T, Harris, SE, van Heemst, D, Heijer, Mden, Hicks, AA, Hollander, Wden, Homuth, G, Hui, J, Ikram, AM, Ittermann, T, Jensen, RA, Jing, J, J Jukema, W, Kajantie, E, Kamatani, Y, Kasbohm, E, Kaufman, J-M, Kiemeney, LA, Kloppenburg, M, Kronenberg, F, Kubo, M, Lahti, J, Lapauw, B, Li, S, Liewald, DCM, Lim, EMun, Linneberg, A, Marina, M, Mascalzoni, D, Matsuda, K, Medenwald, D, Meisinger, C, Meulenbelt, I, De Meyer, T, Meyer zu Schwabedissen, HE, Mikolajczyk, R, Moed, M, Netea-Maier, RT, Nolte, IM, Okada, Y, Pala, M, Pattaro, C, Pedersen, O, Petersmann, A, Porcu, E, Postmus, I, Pramstaller, PP, Psaty, BM, Ramos, YFM, Rawal, R, Redmond, P, J Richards, B, Rietzschel, ER, Rivadeneira, F, Roef, G, Rotter, JI, Sala, CF, Schlessinger, D, Selvin, E, P Slagboom, E, Soranzo, N, Sørensen, TIA, Spector, TD, Starr, JM, Stott, DJ, Taes, Y, Taliun, D, Tanaka, T, Thuesen, B, Tiller, D, Toniolo, D, Uitterlinden, AG, W Visser, E, Walsh, JP, Wilson, SG, Wolffenbuttel, BHR, Yang, Q, Zheng, H-F, Cappola, A, Peeters, RP, Naitza, S, Völzke, H, Sanna, S, Köttgen, A, Visser, TJ, Medici, M |
| Corporate/Institutional Authors | LifeLines Cohort Study, |
| Journal | Nat Commun |
| Volume | 9 |
| Issue | 1 |
| Pagination | 4455 |
| Date Published | 2018 10 26 |
| ISSN | 2041-1723 |
| Abstract | <p>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.</p> |
| DOI | 10.1038/s41467-018-06356-1 |
| Alternate Journal | Nat Commun |
| PubMed ID | 30367059 |
| PubMed Central ID | PMC6203810 |
ePub date:
18/10