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Variants associating with uterine leiomyoma highlight genetic background shared by various cancers and hormone-related traits
Uterine leiomyomas are common benign tumors of the myometrium. We performed a meta-analysis of two genome-wide association studies of leiomyoma in European women (16,595 cases and 523,330 controls), uncovering 21 variants at 16 loci that associate with the disease. Five variants were previously repo...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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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/PMC6128903/ https://www.ncbi.nlm.nih.gov/pubmed/30194396 http://dx.doi.org/10.1038/s41467-018-05428-6 |
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| author | Rafnar, Thorunn Gunnarsson, Bjarni Stefansson, Olafur A. Sulem, Patrick Ingason, Andres Frigge, Michael L. Stefansdottir, Lilja Sigurdsson, Jon K. Tragante, Vinicius Steinthorsdottir, Valgerdur Styrkarsdottir, Unnur Stacey, Simon N. Gudmundsson, Julius Arnadottir, Gudny A. Oddsson, Asmundur Zink, Florian Halldorsson, Gisli Sveinbjornsson, Gardar Kristjansson, Ragnar P. Davidsson, Olafur B. Salvarsdottir, Anna Thoroddsen, Asgeir Helgadottir, Elisabet A. Kristjansdottir, Katrin Ingthorsson, Orri Gudmundsson, Valur Geirsson, Reynir T. Arnadottir, Ragnheidur Gudbjartsson, Daniel F. Masson, Gisli Asselbergs, Folkert W. Jonasson, Jon G. Olafsson, Karl Thorsteinsdottir, Unnur Halldorsson, Bjarni V. Thorleifsson, Gudmar Stefansson, Kari |
| author_facet | Rafnar, Thorunn Gunnarsson, Bjarni Stefansson, Olafur A. Sulem, Patrick Ingason, Andres Frigge, Michael L. Stefansdottir, Lilja Sigurdsson, Jon K. Tragante, Vinicius Steinthorsdottir, Valgerdur Styrkarsdottir, Unnur Stacey, Simon N. Gudmundsson, Julius Arnadottir, Gudny A. Oddsson, Asmundur Zink, Florian Halldorsson, Gisli Sveinbjornsson, Gardar Kristjansson, Ragnar P. Davidsson, Olafur B. Salvarsdottir, Anna Thoroddsen, Asgeir Helgadottir, Elisabet A. Kristjansdottir, Katrin Ingthorsson, Orri Gudmundsson, Valur Geirsson, Reynir T. Arnadottir, Ragnheidur Gudbjartsson, Daniel F. Masson, Gisli Asselbergs, Folkert W. Jonasson, Jon G. Olafsson, Karl Thorsteinsdottir, Unnur Halldorsson, Bjarni V. Thorleifsson, Gudmar Stefansson, Kari |
| author_sort | Rafnar, Thorunn |
| collection | PubMed |
| description | Uterine leiomyomas are common benign tumors of the myometrium. We performed a meta-analysis of two genome-wide association studies of leiomyoma in European women (16,595 cases and 523,330 controls), uncovering 21 variants at 16 loci that associate with the disease. Five variants were previously reported to confer risk of various malignant or benign tumors (rs78378222 in TP53, rs10069690 in TERT, rs1800057 and rs1801516 in ATM, and rs7907606 at OBFC1) and four signals are located at established risk loci for hormone-related traits (endometriosis and breast cancer) at 1q36.12 (CDC42/WNT4), 2p25.1 (GREB1), 20p12.3 (MCM8), and 6q26.2 (SYNE1/ESR1). Polygenic score for leiomyoma, computed using UKB data, is significantly correlated with risk of cancer in the Icelandic population. Functional annotation suggests that the non-coding risk variants affect multiple genes, including ESR1. Our results provide insights into the genetic background of leiomyoma that are shared by other benign and malignant tumors and highlight the role of hormones in leiomyoma growth. |
| format | Online Article Text |
| id | pubmed-6128903 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2018 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-61289032018-09-10 Variants associating with uterine leiomyoma highlight genetic background shared by various cancers and hormone-related traits Rafnar, Thorunn Gunnarsson, Bjarni Stefansson, Olafur A. Sulem, Patrick Ingason, Andres Frigge, Michael L. Stefansdottir, Lilja Sigurdsson, Jon K. Tragante, Vinicius Steinthorsdottir, Valgerdur Styrkarsdottir, Unnur Stacey, Simon N. Gudmundsson, Julius Arnadottir, Gudny A. Oddsson, Asmundur Zink, Florian Halldorsson, Gisli Sveinbjornsson, Gardar Kristjansson, Ragnar P. Davidsson, Olafur B. Salvarsdottir, Anna Thoroddsen, Asgeir Helgadottir, Elisabet A. Kristjansdottir, Katrin Ingthorsson, Orri Gudmundsson, Valur Geirsson, Reynir T. Arnadottir, Ragnheidur Gudbjartsson, Daniel F. Masson, Gisli Asselbergs, Folkert W. Jonasson, Jon G. Olafsson, Karl Thorsteinsdottir, Unnur Halldorsson, Bjarni V. Thorleifsson, Gudmar Stefansson, Kari Nat Commun Article Uterine leiomyomas are common benign tumors of the myometrium. We performed a meta-analysis of two genome-wide association studies of leiomyoma in European women (16,595 cases and 523,330 controls), uncovering 21 variants at 16 loci that associate with the disease. Five variants were previously reported to confer risk of various malignant or benign tumors (rs78378222 in TP53, rs10069690 in TERT, rs1800057 and rs1801516 in ATM, and rs7907606 at OBFC1) and four signals are located at established risk loci for hormone-related traits (endometriosis and breast cancer) at 1q36.12 (CDC42/WNT4), 2p25.1 (GREB1), 20p12.3 (MCM8), and 6q26.2 (SYNE1/ESR1). Polygenic score for leiomyoma, computed using UKB data, is significantly correlated with risk of cancer in the Icelandic population. Functional annotation suggests that the non-coding risk variants affect multiple genes, including ESR1. Our results provide insights into the genetic background of leiomyoma that are shared by other benign and malignant tumors and highlight the role of hormones in leiomyoma growth. Nature Publishing Group UK 2018-09-07 /pmc/articles/PMC6128903/ /pubmed/30194396 http://dx.doi.org/10.1038/s41467-018-05428-6 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 Rafnar, Thorunn Gunnarsson, Bjarni Stefansson, Olafur A. Sulem, Patrick Ingason, Andres Frigge, Michael L. Stefansdottir, Lilja Sigurdsson, Jon K. Tragante, Vinicius Steinthorsdottir, Valgerdur Styrkarsdottir, Unnur Stacey, Simon N. Gudmundsson, Julius Arnadottir, Gudny A. Oddsson, Asmundur Zink, Florian Halldorsson, Gisli Sveinbjornsson, Gardar Kristjansson, Ragnar P. Davidsson, Olafur B. Salvarsdottir, Anna Thoroddsen, Asgeir Helgadottir, Elisabet A. Kristjansdottir, Katrin Ingthorsson, Orri Gudmundsson, Valur Geirsson, Reynir T. Arnadottir, Ragnheidur Gudbjartsson, Daniel F. Masson, Gisli Asselbergs, Folkert W. Jonasson, Jon G. Olafsson, Karl Thorsteinsdottir, Unnur Halldorsson, Bjarni V. Thorleifsson, Gudmar Stefansson, Kari Variants associating with uterine leiomyoma highlight genetic background shared by various cancers and hormone-related traits |
| title | Variants associating with uterine leiomyoma highlight genetic background shared by various cancers and hormone-related traits |
| title_full | Variants associating with uterine leiomyoma highlight genetic background shared by various cancers and hormone-related traits |
| title_fullStr | Variants associating with uterine leiomyoma highlight genetic background shared by various cancers and hormone-related traits |
| title_full_unstemmed | Variants associating with uterine leiomyoma highlight genetic background shared by various cancers and hormone-related traits |
| title_short | Variants associating with uterine leiomyoma highlight genetic background shared by various cancers and hormone-related traits |
| title_sort | variants associating with uterine leiomyoma highlight genetic background shared by various cancers and hormone-related traits |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6128903/ https://www.ncbi.nlm.nih.gov/pubmed/30194396 http://dx.doi.org/10.1038/s41467-018-05428-6 |
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