Cargando…
GWAS of thyroid stimulating hormone highlights pleiotropic effects and inverse association with thyroid cancer
Thyroid stimulating hormone (TSH) is critical for normal development and metabolism. To better understand the genetic contribution to TSH levels, we conduct a GWAS meta-analysis at 22.4 million genetic markers in up to 119,715 individuals and identify 74 genome-wide significant loci for TSH, of whic...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group UK
2020
|
| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414135/ https://www.ncbi.nlm.nih.gov/pubmed/32769997 http://dx.doi.org/10.1038/s41467-020-17718-z |
| _version_ | 1783568917832138752 |
|---|---|
| author | Zhou, Wei Brumpton, Ben Kabil, Omer Gudmundsson, Julius Thorleifsson, Gudmar Weinstock, Josh Zawistowski, Matthew Nielsen, Jonas B. Chaker, Layal Medici, Marco Teumer, Alexander Naitza, Silvia Sanna, Serena Schultheiss, Ulla T. Cappola, Anne Karjalainen, Juha Kurki, Mitja Oneka, Morgan Taylor, Peter Fritsche, Lars G. Graham, Sarah E. Wolford, Brooke N. Overton, William Rasheed, Humaira Haug, Eirin B. Gabrielsen, Maiken E. Skogholt, Anne Heidi Surakka, Ida Davey Smith, George Pandit, Anita Roychowdhury, Tanmoy Hornsby, Whitney E. Jonasson, Jon G. Senter, Leigha Liyanarachchi, Sandya Ringel, Matthew D. Xu, Li Kiemeney, Lambertus A. He, Huiling Netea-Maier, Romana T. Mayordomo, Jose I. Plantinga, Theo S. Hrafnkelsson, Jon Hjartarson, Hannes Sturgis, Erich M. Palotie, Aarno Daly, Mark Citterio, Cintia E. Arvan, Peter Brummett, Chad M. Boehnke, Michael de la Chapelle, Albert Stefansson, Kari Hveem, Kristian Willer, Cristen J. Åsvold, Bjørn Olav |
| author_facet | Zhou, Wei Brumpton, Ben Kabil, Omer Gudmundsson, Julius Thorleifsson, Gudmar Weinstock, Josh Zawistowski, Matthew Nielsen, Jonas B. Chaker, Layal Medici, Marco Teumer, Alexander Naitza, Silvia Sanna, Serena Schultheiss, Ulla T. Cappola, Anne Karjalainen, Juha Kurki, Mitja Oneka, Morgan Taylor, Peter Fritsche, Lars G. Graham, Sarah E. Wolford, Brooke N. Overton, William Rasheed, Humaira Haug, Eirin B. Gabrielsen, Maiken E. Skogholt, Anne Heidi Surakka, Ida Davey Smith, George Pandit, Anita Roychowdhury, Tanmoy Hornsby, Whitney E. Jonasson, Jon G. Senter, Leigha Liyanarachchi, Sandya Ringel, Matthew D. Xu, Li Kiemeney, Lambertus A. He, Huiling Netea-Maier, Romana T. Mayordomo, Jose I. Plantinga, Theo S. Hrafnkelsson, Jon Hjartarson, Hannes Sturgis, Erich M. Palotie, Aarno Daly, Mark Citterio, Cintia E. Arvan, Peter Brummett, Chad M. Boehnke, Michael de la Chapelle, Albert Stefansson, Kari Hveem, Kristian Willer, Cristen J. Åsvold, Bjørn Olav |
| author_sort | Zhou, Wei |
| collection | PubMed |
| description | Thyroid stimulating hormone (TSH) is critical for normal development and metabolism. To better understand the genetic contribution to TSH levels, we conduct a GWAS meta-analysis at 22.4 million genetic markers in up to 119,715 individuals and identify 74 genome-wide significant loci for TSH, of which 28 are previously unreported. Functional experiments show that the thyroglobulin protein-altering variants P118L and G67S impact thyroglobulin secretion. Phenome-wide association analysis in the UK Biobank demonstrates the pleiotropic effects of TSH-associated variants and a polygenic score for higher TSH levels is associated with a reduced risk of thyroid cancer in the UK Biobank and three other independent studies. Two-sample Mendelian randomization using TSH index variants as instrumental variables suggests a protective effect of higher TSH levels (indicating lower thyroid function) on risk of thyroid cancer and goiter. Our findings highlight the pleiotropic effects of TSH-associated variants on thyroid function and growth of malignant and benign thyroid tumors. |
| format | Online Article Text |
| id | pubmed-7414135 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2020 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-74141352020-08-17 GWAS of thyroid stimulating hormone highlights pleiotropic effects and inverse association with thyroid cancer Zhou, Wei Brumpton, Ben Kabil, Omer Gudmundsson, Julius Thorleifsson, Gudmar Weinstock, Josh Zawistowski, Matthew Nielsen, Jonas B. Chaker, Layal Medici, Marco Teumer, Alexander Naitza, Silvia Sanna, Serena Schultheiss, Ulla T. Cappola, Anne Karjalainen, Juha Kurki, Mitja Oneka, Morgan Taylor, Peter Fritsche, Lars G. Graham, Sarah E. Wolford, Brooke N. Overton, William Rasheed, Humaira Haug, Eirin B. Gabrielsen, Maiken E. Skogholt, Anne Heidi Surakka, Ida Davey Smith, George Pandit, Anita Roychowdhury, Tanmoy Hornsby, Whitney E. Jonasson, Jon G. Senter, Leigha Liyanarachchi, Sandya Ringel, Matthew D. Xu, Li Kiemeney, Lambertus A. He, Huiling Netea-Maier, Romana T. Mayordomo, Jose I. Plantinga, Theo S. Hrafnkelsson, Jon Hjartarson, Hannes Sturgis, Erich M. Palotie, Aarno Daly, Mark Citterio, Cintia E. Arvan, Peter Brummett, Chad M. Boehnke, Michael de la Chapelle, Albert Stefansson, Kari Hveem, Kristian Willer, Cristen J. Åsvold, Bjørn Olav Nat Commun Article Thyroid stimulating hormone (TSH) is critical for normal development and metabolism. To better understand the genetic contribution to TSH levels, we conduct a GWAS meta-analysis at 22.4 million genetic markers in up to 119,715 individuals and identify 74 genome-wide significant loci for TSH, of which 28 are previously unreported. Functional experiments show that the thyroglobulin protein-altering variants P118L and G67S impact thyroglobulin secretion. Phenome-wide association analysis in the UK Biobank demonstrates the pleiotropic effects of TSH-associated variants and a polygenic score for higher TSH levels is associated with a reduced risk of thyroid cancer in the UK Biobank and three other independent studies. Two-sample Mendelian randomization using TSH index variants as instrumental variables suggests a protective effect of higher TSH levels (indicating lower thyroid function) on risk of thyroid cancer and goiter. Our findings highlight the pleiotropic effects of TSH-associated variants on thyroid function and growth of malignant and benign thyroid tumors. Nature Publishing Group UK 2020-08-07 /pmc/articles/PMC7414135/ /pubmed/32769997 http://dx.doi.org/10.1038/s41467-020-17718-z Text en © The Author(s) 2020, corrected publication 2021 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . |
| spellingShingle | Article Zhou, Wei Brumpton, Ben Kabil, Omer Gudmundsson, Julius Thorleifsson, Gudmar Weinstock, Josh Zawistowski, Matthew Nielsen, Jonas B. Chaker, Layal Medici, Marco Teumer, Alexander Naitza, Silvia Sanna, Serena Schultheiss, Ulla T. Cappola, Anne Karjalainen, Juha Kurki, Mitja Oneka, Morgan Taylor, Peter Fritsche, Lars G. Graham, Sarah E. Wolford, Brooke N. Overton, William Rasheed, Humaira Haug, Eirin B. Gabrielsen, Maiken E. Skogholt, Anne Heidi Surakka, Ida Davey Smith, George Pandit, Anita Roychowdhury, Tanmoy Hornsby, Whitney E. Jonasson, Jon G. Senter, Leigha Liyanarachchi, Sandya Ringel, Matthew D. Xu, Li Kiemeney, Lambertus A. He, Huiling Netea-Maier, Romana T. Mayordomo, Jose I. Plantinga, Theo S. Hrafnkelsson, Jon Hjartarson, Hannes Sturgis, Erich M. Palotie, Aarno Daly, Mark Citterio, Cintia E. Arvan, Peter Brummett, Chad M. Boehnke, Michael de la Chapelle, Albert Stefansson, Kari Hveem, Kristian Willer, Cristen J. Åsvold, Bjørn Olav GWAS of thyroid stimulating hormone highlights pleiotropic effects and inverse association with thyroid cancer |
| title | GWAS of thyroid stimulating hormone highlights pleiotropic effects and inverse association with thyroid cancer |
| title_full | GWAS of thyroid stimulating hormone highlights pleiotropic effects and inverse association with thyroid cancer |
| title_fullStr | GWAS of thyroid stimulating hormone highlights pleiotropic effects and inverse association with thyroid cancer |
| title_full_unstemmed | GWAS of thyroid stimulating hormone highlights pleiotropic effects and inverse association with thyroid cancer |
| title_short | GWAS of thyroid stimulating hormone highlights pleiotropic effects and inverse association with thyroid cancer |
| title_sort | gwas of thyroid stimulating hormone highlights pleiotropic effects and inverse association with thyroid cancer |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414135/ https://www.ncbi.nlm.nih.gov/pubmed/32769997 http://dx.doi.org/10.1038/s41467-020-17718-z |
| work_keys_str_mv | AT zhouwei gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT brumptonben gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT kabilomer gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT gudmundssonjulius gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT thorleifssongudmar gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT weinstockjosh gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT zawistowskimatthew gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT nielsenjonasb gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT chakerlayal gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT medicimarco gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT teumeralexander gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT naitzasilvia gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT sannaserena gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT schultheissullat gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT cappolaanne gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT karjalainenjuha gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT kurkimitja gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT onekamorgan gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT taylorpeter gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT fritschelarsg gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT grahamsarahe gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT wolfordbrooken gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT overtonwilliam gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT rasheedhumaira gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT haugeirinb gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT gabrielsenmaikene gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT skogholtanneheidi gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT surakkaida gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT daveysmithgeorge gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT panditanita gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT roychowdhurytanmoy gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT hornsbywhitneye gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT jonassonjong gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT senterleigha gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT liyanarachchisandya gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT ringelmatthewd gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT xuli gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT kiemeneylambertusa gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT hehuiling gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT neteamaierromanat gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT mayordomojosei gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT plantingatheos gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT hrafnkelssonjon gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT hjartarsonhannes gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT sturgiserichm gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT palotieaarno gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT dalymark gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT citteriocintiae gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT arvanpeter gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT brummettchadm gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT boehnkemichael gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT delachapellealbert gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT stefanssonkari gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT hveemkristian gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT willercristenj gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer AT asvoldbjørnolav gwasofthyroidstimulatinghormonehighlightspleiotropiceffectsandinverseassociationwiththyroidcancer |