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Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation
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 deter...
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group UK
2018
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6203810/ https://www.ncbi.nlm.nih.gov/pubmed/30367059 http://dx.doi.org/10.1038/s41467-018-06356-1 |
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| author | Teumer, Alexander Chaker, Layal Groeneweg, Stefan Li, Yong Di Munno, Celia Barbieri, Caterina Schultheiss, Ulla T. Traglia, Michela Ahluwalia, Tarunveer S. Akiyama, Masato Appel, Emil Vincent R. Arking, Dan E. Arnold, Alice Astrup, Arne Beekman, Marian Beilby, John P. Bekaert, Sofie Boerwinkle, Eric Brown, Suzanne J. De Buyzere, Marc Campbell, Purdey J. Ceresini, Graziano Cerqueira, Charlotte Cucca, Francesco Deary, Ian J. Deelen, Joris Eckardt, Kai-Uwe Ekici, Arif B. Eriksson, Johan G. Ferrrucci, Luigi Fiers, Tom Fiorillo, Edoardo Ford, Ian Fox, Caroline S. Fuchsberger, Christian Galesloot, Tessel E. Gieger, Christian Gögele, Martin De Grandi, Alessandro Grarup, Niels Greiser, Karin Halina Haljas, Kadri Hansen, Torben Harris, Sarah E. van Heemst, Diana den Heijer, Martin Hicks, Andrew A. den Hollander, Wouter Homuth, Georg Hui, Jennie Ikram, M. Arfan Ittermann, Till Jensen, Richard A. Jing, Jiaojiao Jukema, J. Wouter Kajantie, Eero Kamatani, Yoichiro Kasbohm, Elisa Kaufman, Jean-Marc Kiemeney, Lambertus A. Kloppenburg, Margreet Kronenberg, Florian Kubo, Michiaki Lahti, Jari Lapauw, Bruno Li, Shuo Liewald, David C. M. Lim, Ee Mun Linneberg, Allan Marina, Michela Mascalzoni, Deborah Matsuda, Koichi Medenwald, Daniel Meisinger, Christa Meulenbelt, Ingrid De Meyer, Tim Meyer zu Schwabedissen, Henriette E. Mikolajczyk, Rafael Moed, Matthijs Netea-Maier, Romana T. Nolte, Ilja M. Okada, Yukinori Pala, Mauro Pattaro, Cristian Pedersen, Oluf Petersmann, Astrid Porcu, Eleonora Postmus, Iris Pramstaller, Peter P. Psaty, Bruce M. Ramos, Yolande F. M. Rawal, Rajesh Redmond, Paul Richards, J. Brent Rietzschel, Ernst R. Rivadeneira, Fernando Roef, Greet Rotter, Jerome I. Sala, Cinzia F. Schlessinger, David Selvin, Elizabeth Slagboom, P. Eline Soranzo, Nicole Sørensen, Thorkild I. A. Spector, Timothy D. Starr, John M. Stott, David J. Taes, Youri Taliun, Daniel Tanaka, Toshiko Thuesen, Betina Tiller, Daniel Toniolo, Daniela Uitterlinden, Andre G. Visser, W. Edward Walsh, John P. Wilson, Scott G. Wolffenbuttel, Bruce H. R. Yang, Qiong Zheng, Hou-Feng Cappola, Anne Peeters, Robin P. Naitza, Silvia Völzke, Henry Sanna, Serena Köttgen, Anna Visser, Theo J. Medici, Marco |
| author_facet | Teumer, Alexander Chaker, Layal Groeneweg, Stefan Li, Yong Di Munno, Celia Barbieri, Caterina Schultheiss, Ulla T. Traglia, Michela Ahluwalia, Tarunveer S. Akiyama, Masato Appel, Emil Vincent R. Arking, Dan E. Arnold, Alice Astrup, Arne Beekman, Marian Beilby, John P. Bekaert, Sofie Boerwinkle, Eric Brown, Suzanne J. De Buyzere, Marc Campbell, Purdey J. Ceresini, Graziano Cerqueira, Charlotte Cucca, Francesco Deary, Ian J. Deelen, Joris Eckardt, Kai-Uwe Ekici, Arif B. Eriksson, Johan G. Ferrrucci, Luigi Fiers, Tom Fiorillo, Edoardo Ford, Ian Fox, Caroline S. Fuchsberger, Christian Galesloot, Tessel E. Gieger, Christian Gögele, Martin De Grandi, Alessandro Grarup, Niels Greiser, Karin Halina Haljas, Kadri Hansen, Torben Harris, Sarah E. van Heemst, Diana den Heijer, Martin Hicks, Andrew A. den Hollander, Wouter Homuth, Georg Hui, Jennie Ikram, M. Arfan Ittermann, Till Jensen, Richard A. Jing, Jiaojiao Jukema, J. Wouter Kajantie, Eero Kamatani, Yoichiro Kasbohm, Elisa Kaufman, Jean-Marc Kiemeney, Lambertus A. Kloppenburg, Margreet Kronenberg, Florian Kubo, Michiaki Lahti, Jari Lapauw, Bruno Li, Shuo Liewald, David C. M. Lim, Ee Mun Linneberg, Allan Marina, Michela Mascalzoni, Deborah Matsuda, Koichi Medenwald, Daniel Meisinger, Christa Meulenbelt, Ingrid De Meyer, Tim Meyer zu Schwabedissen, Henriette E. Mikolajczyk, Rafael Moed, Matthijs Netea-Maier, Romana T. Nolte, Ilja M. Okada, Yukinori Pala, Mauro Pattaro, Cristian Pedersen, Oluf Petersmann, Astrid Porcu, Eleonora Postmus, Iris Pramstaller, Peter P. Psaty, Bruce M. Ramos, Yolande F. M. Rawal, Rajesh Redmond, Paul Richards, J. Brent Rietzschel, Ernst R. Rivadeneira, Fernando Roef, Greet Rotter, Jerome I. Sala, Cinzia F. Schlessinger, David Selvin, Elizabeth Slagboom, P. Eline Soranzo, Nicole Sørensen, Thorkild I. A. Spector, Timothy D. Starr, John M. Stott, David J. Taes, Youri Taliun, Daniel Tanaka, Toshiko Thuesen, Betina Tiller, Daniel Toniolo, Daniela Uitterlinden, Andre G. Visser, W. Edward Walsh, John P. Wilson, Scott G. Wolffenbuttel, Bruce H. R. Yang, Qiong Zheng, Hou-Feng Cappola, Anne Peeters, Robin P. Naitza, Silvia Völzke, Henry Sanna, Serena Köttgen, Anna Visser, Theo J. Medici, Marco |
| author_sort | Teumer, Alexander |
| collection | PubMed |
| description | 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. |
| format | Online Article Text |
| id | pubmed-6203810 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2018 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-62038102018-10-29 Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation Teumer, Alexander Chaker, Layal Groeneweg, Stefan Li, Yong Di Munno, Celia Barbieri, Caterina Schultheiss, Ulla T. Traglia, Michela Ahluwalia, Tarunveer S. Akiyama, Masato Appel, Emil Vincent R. Arking, Dan E. Arnold, Alice Astrup, Arne Beekman, Marian Beilby, John P. Bekaert, Sofie Boerwinkle, Eric Brown, Suzanne J. De Buyzere, Marc Campbell, Purdey J. Ceresini, Graziano Cerqueira, Charlotte Cucca, Francesco Deary, Ian J. Deelen, Joris Eckardt, Kai-Uwe Ekici, Arif B. Eriksson, Johan G. Ferrrucci, Luigi Fiers, Tom Fiorillo, Edoardo Ford, Ian Fox, Caroline S. Fuchsberger, Christian Galesloot, Tessel E. Gieger, Christian Gögele, Martin De Grandi, Alessandro Grarup, Niels Greiser, Karin Halina Haljas, Kadri Hansen, Torben Harris, Sarah E. van Heemst, Diana den Heijer, Martin Hicks, Andrew A. den Hollander, Wouter Homuth, Georg Hui, Jennie Ikram, M. Arfan Ittermann, Till Jensen, Richard A. Jing, Jiaojiao Jukema, J. Wouter Kajantie, Eero Kamatani, Yoichiro Kasbohm, Elisa Kaufman, Jean-Marc Kiemeney, Lambertus A. Kloppenburg, Margreet Kronenberg, Florian Kubo, Michiaki Lahti, Jari Lapauw, Bruno Li, Shuo Liewald, David C. M. Lim, Ee Mun Linneberg, Allan Marina, Michela Mascalzoni, Deborah Matsuda, Koichi Medenwald, Daniel Meisinger, Christa Meulenbelt, Ingrid De Meyer, Tim Meyer zu Schwabedissen, Henriette E. Mikolajczyk, Rafael Moed, Matthijs Netea-Maier, Romana T. Nolte, Ilja M. Okada, Yukinori Pala, Mauro Pattaro, Cristian Pedersen, Oluf Petersmann, Astrid Porcu, Eleonora Postmus, Iris Pramstaller, Peter P. Psaty, Bruce M. Ramos, Yolande F. M. Rawal, Rajesh Redmond, Paul Richards, J. Brent Rietzschel, Ernst R. Rivadeneira, Fernando Roef, Greet Rotter, Jerome I. Sala, Cinzia F. Schlessinger, David Selvin, Elizabeth Slagboom, P. Eline Soranzo, Nicole Sørensen, Thorkild I. A. Spector, Timothy D. Starr, John M. Stott, David J. Taes, Youri Taliun, Daniel Tanaka, Toshiko Thuesen, Betina Tiller, Daniel Toniolo, Daniela Uitterlinden, Andre G. Visser, W. Edward Walsh, John P. Wilson, Scott G. Wolffenbuttel, Bruce H. R. Yang, Qiong Zheng, Hou-Feng Cappola, Anne Peeters, Robin P. Naitza, Silvia Völzke, Henry Sanna, Serena Köttgen, Anna Visser, Theo J. Medici, Marco Nat Commun Article 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. Nature Publishing Group UK 2018-10-26 /pmc/articles/PMC6203810/ /pubmed/30367059 http://dx.doi.org/10.1038/s41467-018-06356-1 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| spellingShingle | Article Teumer, Alexander Chaker, Layal Groeneweg, Stefan Li, Yong Di Munno, Celia Barbieri, Caterina Schultheiss, Ulla T. Traglia, Michela Ahluwalia, Tarunveer S. Akiyama, Masato Appel, Emil Vincent R. Arking, Dan E. Arnold, Alice Astrup, Arne Beekman, Marian Beilby, John P. Bekaert, Sofie Boerwinkle, Eric Brown, Suzanne J. De Buyzere, Marc Campbell, Purdey J. Ceresini, Graziano Cerqueira, Charlotte Cucca, Francesco Deary, Ian J. Deelen, Joris Eckardt, Kai-Uwe Ekici, Arif B. Eriksson, Johan G. Ferrrucci, Luigi Fiers, Tom Fiorillo, Edoardo Ford, Ian Fox, Caroline S. Fuchsberger, Christian Galesloot, Tessel E. Gieger, Christian Gögele, Martin De Grandi, Alessandro Grarup, Niels Greiser, Karin Halina Haljas, Kadri Hansen, Torben Harris, Sarah E. van Heemst, Diana den Heijer, Martin Hicks, Andrew A. den Hollander, Wouter Homuth, Georg Hui, Jennie Ikram, M. Arfan Ittermann, Till Jensen, Richard A. Jing, Jiaojiao Jukema, J. Wouter Kajantie, Eero Kamatani, Yoichiro Kasbohm, Elisa Kaufman, Jean-Marc Kiemeney, Lambertus A. Kloppenburg, Margreet Kronenberg, Florian Kubo, Michiaki Lahti, Jari Lapauw, Bruno Li, Shuo Liewald, David C. M. Lim, Ee Mun Linneberg, Allan Marina, Michela Mascalzoni, Deborah Matsuda, Koichi Medenwald, Daniel Meisinger, Christa Meulenbelt, Ingrid De Meyer, Tim Meyer zu Schwabedissen, Henriette E. Mikolajczyk, Rafael Moed, Matthijs Netea-Maier, Romana T. Nolte, Ilja M. Okada, Yukinori Pala, Mauro Pattaro, Cristian Pedersen, Oluf Petersmann, Astrid Porcu, Eleonora Postmus, Iris Pramstaller, Peter P. Psaty, Bruce M. Ramos, Yolande F. M. Rawal, Rajesh Redmond, Paul Richards, J. Brent Rietzschel, Ernst R. Rivadeneira, Fernando Roef, Greet Rotter, Jerome I. Sala, Cinzia F. Schlessinger, David Selvin, Elizabeth Slagboom, P. Eline Soranzo, Nicole Sørensen, Thorkild I. A. Spector, Timothy D. Starr, John M. Stott, David J. Taes, Youri Taliun, Daniel Tanaka, Toshiko Thuesen, Betina Tiller, Daniel Toniolo, Daniela Uitterlinden, Andre G. Visser, W. Edward Walsh, John P. Wilson, Scott G. Wolffenbuttel, Bruce H. R. Yang, Qiong Zheng, Hou-Feng Cappola, Anne Peeters, Robin P. Naitza, Silvia Völzke, Henry Sanna, Serena Köttgen, Anna Visser, Theo J. Medici, Marco Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation |
| title | Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation |
| title_full | Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation |
| title_fullStr | Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation |
| title_full_unstemmed | Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation |
| title_short | Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation |
| title_sort | genome-wide analyses identify a role for slc17a4 and aadat in thyroid hormone regulation |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6203810/ https://www.ncbi.nlm.nih.gov/pubmed/30367059 http://dx.doi.org/10.1038/s41467-018-06356-1 |
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