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

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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.
Keywords
PARTICIPANT DATA-ANALYSIS, MONOCARBOXYLATE TRANSPORTER-8, SUBCLINICAL HYPOTHYROIDISM, ATRIAL-FIBRILLATION, REFERENCE RANGE, ASSOCIATION, RISK, IDENTIFICATION, POPULATION, DISEASE

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MLA
Teumer, Alexander, Layal Chaker, Stefan Groeneweg, et al. “Genome-wide Analyses Identify a Role for SLC17A4 and AADAT in Thyroid Hormone Regulation.” NATURE COMMUNICATIONS 9 (2018): n. pag. Print.
APA
Teumer, A., Chaker, L., Groeneweg, S., Li, Y., Di Munno, C., Barbieri, C., Schultheiss, U. T., et al. (2018). Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation. NATURE COMMUNICATIONS, 9.
Chicago author-date
Teumer, Alexander, Layal Chaker, Stefan Groeneweg, Yong Li, Celia Di Munno, Caterina Barbieri, Ulla T Schultheiss, et al. 2018. “Genome-wide Analyses Identify a Role for SLC17A4 and AADAT in Thyroid Hormone Regulation.” Nature Communications 9.
Chicago author-date (all authors)
Teumer, Alexander, Layal Chaker, Stefan Groeneweg, Yong Li, Celia Di Munno, Caterina Barbieri, Ulla T Schultheiss, Michela Traglia, Tarunveer S Ahluwalia, Masato Akiyama, Emil Vincent R Appel, Dan E Arking, Alice Arnold, Arne Astrup, Marian Beekman, John P Beilby, Sofie Bekaert, Eric Boerwinkle, Suzanne J Brown, Marc De Buyzere, Purdey J Campbell, Graziano Ceresini, Charlotte Cerqueira, Francesco Cucca, Ian J Deary, Joris Deelen, Kai-Uwe Eckardt, Arif B Ekici, Johan G Eriksson, Luigi Ferrrucci, Tom Fiers, Edoardo Fiorillo, Ian Ford, Caroline S Fox, Christian Fuchsberger, Tessel E Galesloot, Christian Gieger, Martin Gögele, Alessandro De Grandi, Niels Grarup, Karin Halina Greiser, Kadri Haljas, Torben Hansen, Sarah E Harris, Diana van Heemst, Martin den Heijer, Andrew A Hicks, Wouter den Hollander, Georg Homuth, Jennie Hui, M Arfan Ikram, Till Ittermann, Richard A Jensen, Jiaojiao Jing, J Wouter Jukema, Eero Kajantie, Yoichiro Kamatani, Elisa Kasbohm, Jean Kaufman, Lambertus A Kiemeney, Margreet Kloppenburg, Florian Kronenberg, Michiaki Kubo, Jari Lahti, Bruno Lapauw, Shuo Li, David CM Liewald, Ee Mun Lim, Allan Linneberg, Michela Marina, Deborah Mascalzoni, Koichi Matsuda, Daniel Medenwald, Christa Meisinger, Ingrid Meulenbelt, Tim De Meyer, Henriette E Meyer zu Schwabedissen, Rafael Mikolajczyk, Matthijs Moed, Romana T Netea-Maier, Ilja M Nolte, Yukinori Okada, Mauro Pala, Cristian Pattaro, Oluf Pedersen, Astrid Petersmann, Eleonora Porcu, Iris Postmus, Peter P Pramstaller, Bruce M Psaty, Yolande FM Ramos, Rajesh Rawal, Paul Redmond, J Brent Richards, Ernst Rietzschel, Fernando Rivadeneira, GREET ROEF, Jerome I Rotter, Cinzia F Sala, David Schlessinger, Elizabeth Selvin, P Eline Slagboom, Nicole Soranzo, Thorkild IA Sørensen, Timothy D Spector, John M Starr, David J Stott, Youri Taes, Daniel Taliun, Toshiko Tanaka, Betina Thuesen, Daniel Tiller, Daniela Toniolo, Andre G Uitterlinden, W Edward Visser, John P Walsh, Scott G Wilson, Bruce HR Wolffenbuttel, Qiong Yang, Hou-Feng Zheng, Anne Cappola, Robin P Peeters, Silvia Naitza, Henry Völzke, Serena Sanna, Anna Köttgen, Theo J Visser, and Marco Medici. 2018. “Genome-wide Analyses Identify a Role for SLC17A4 and AADAT in Thyroid Hormone Regulation.” Nature Communications 9.
Vancouver
1.
Teumer A, Chaker L, Groeneweg S, Li Y, Di Munno C, Barbieri C, et al. Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation. NATURE COMMUNICATIONS. 2018;9.
IEEE
[1]
A. Teumer et al., “Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation,” NATURE COMMUNICATIONS, vol. 9, 2018.
@article{8579152,
  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.},
  articleno    = {4455},
  author       = {Teumer, Alexander and Chaker, Layal and Groeneweg, Stefan and Li, Yong and Di Munno, Celia and Barbieri, Caterina and Schultheiss, Ulla T and Traglia, Michela and Ahluwalia, Tarunveer S and Akiyama, Masato and Appel, Emil Vincent R and Arking, Dan E and Arnold, Alice and Astrup, Arne and Beekman, Marian and Beilby, John P and Bekaert, Sofie and Boerwinkle, Eric and Brown, Suzanne J and De Buyzere, Marc and Campbell, Purdey J and Ceresini, Graziano and Cerqueira, Charlotte and Cucca, Francesco and Deary, Ian J and Deelen, Joris and Eckardt, Kai-Uwe and Ekici, Arif B and Eriksson, Johan G and Ferrrucci, Luigi and Fiers, Tom and Fiorillo, Edoardo and Ford, Ian and Fox, Caroline S and Fuchsberger, Christian and Galesloot, Tessel E and Gieger, Christian and Gögele, Martin and De Grandi, Alessandro and Grarup, Niels and Greiser, Karin Halina and Haljas, Kadri and Hansen, Torben and Harris, Sarah E and van Heemst, Diana and den Heijer, Martin and Hicks, Andrew A and den Hollander, Wouter and Homuth, Georg and Hui, Jennie and Ikram, M Arfan and Ittermann, Till and Jensen, Richard A and Jing, Jiaojiao and Jukema, J Wouter and Kajantie, Eero and Kamatani, Yoichiro and Kasbohm, Elisa and Kaufman, Jean and Kiemeney, Lambertus A and Kloppenburg, Margreet and Kronenberg, Florian and Kubo, Michiaki and Lahti, Jari and Lapauw, Bruno and Li, Shuo and Liewald, David CM and Lim, Ee Mun and Linneberg, Allan and Marina, Michela and Mascalzoni, Deborah and Matsuda, Koichi and Medenwald, Daniel and Meisinger, Christa and Meulenbelt, Ingrid and De Meyer, Tim and Meyer zu Schwabedissen, Henriette E and Mikolajczyk, Rafael and Moed, Matthijs and Netea-Maier, Romana T and Nolte, Ilja M and Okada, Yukinori and Pala, Mauro and Pattaro, Cristian and Pedersen, Oluf and Petersmann, Astrid and Porcu, Eleonora and Postmus, Iris and Pramstaller, Peter P and Psaty, Bruce M and Ramos, Yolande FM and Rawal, Rajesh and Redmond, Paul and Richards, J Brent and Rietzschel, Ernst and Rivadeneira, Fernando and ROEF, GREET and Rotter, Jerome I and Sala, Cinzia F and Schlessinger, David and Selvin, Elizabeth and Slagboom, P Eline and Soranzo, Nicole and Sørensen, Thorkild IA and Spector, Timothy D and Starr, John M and Stott, David J and Taes, Youri and Taliun, Daniel and Tanaka, Toshiko and Thuesen, Betina and Tiller, Daniel and Toniolo, Daniela and Uitterlinden, Andre G and Visser, W Edward and Walsh, John P and Wilson, Scott G and Wolffenbuttel, Bruce HR and Yang, Qiong and Zheng, Hou-Feng and Cappola, Anne and Peeters, Robin P and Naitza, Silvia and Völzke, Henry and Sanna, Serena and Köttgen, Anna and Visser, Theo J and Medici, Marco},
  issn         = {2041-1723},
  journal      = {NATURE COMMUNICATIONS},
  keywords     = {PARTICIPANT DATA-ANALYSIS,MONOCARBOXYLATE TRANSPORTER-8,SUBCLINICAL HYPOTHYROIDISM,ATRIAL-FIBRILLATION,REFERENCE RANGE,ASSOCIATION,RISK,IDENTIFICATION,POPULATION,DISEASE},
  language     = {eng},
  pages        = {14},
  title        = {Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation},
  url          = {http://dx.doi.org/10.1038/s41467-018-06356-1},
  volume       = {9},
  year         = {2018},
}

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