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Platelet function is modified by common sequence variation in megakaryocyte super enhancers
Linking non-coding genetic variants associated with the risk of diseases or disease-relevant traits to target genes is a crucial step to realize GWAS potential in the introduction of precision medicine. Here we set out to determine the mechanisms underpinning variant association with platelet quanti...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group
2017
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5511350/ https://www.ncbi.nlm.nih.gov/pubmed/28703137 http://dx.doi.org/10.1038/ncomms16058 |
| _version_ | 1783250324748763136 |
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| author | Petersen, Romina Lambourne, John J. Javierre, Biola M. Grassi, Luigi Kreuzhuber, Roman Ruklisa, Dace Rosa, Isabel M. Tomé, Ana R. Elding, Heather van Geffen, Johanna P. Jiang, Tao Farrow, Samantha Cairns, Jonathan Al-Subaie, Abeer M. Ashford, Sofie Attwood, Antony Batista, Joana Bouman, Heleen Burden, Frances Choudry, Fizzah A. Clarke, Laura Flicek, Paul Garner, Stephen F. Haimel, Matthias Kempster, Carly Ladopoulos, Vasileios Lenaerts, An-Sofie Materek, Paulina M. McKinney, Harriet Meacham, Stuart Mead, Daniel Nagy, Magdolna Penkett, Christopher J. Rendon, Augusto Seyres, Denis Sun, Benjamin Tuna, Salih van der Weide, Marie-Elise Wingett, Steven W. Martens, Joost H. Stegle, Oliver Richardson, Sylvia Vallier, Ludovic Roberts, David J. Freson, Kathleen Wernisch, Lorenz Stunnenberg, Hendrik G. Danesh, John Fraser, Peter Soranzo, Nicole Butterworth, Adam S. Heemskerk, Johan W. Turro, Ernest Spivakov, Mikhail Ouwehand, Willem H. Astle, William J. Downes, Kate Kostadima, Myrto Frontini, Mattia |
| author_facet | Petersen, Romina Lambourne, John J. Javierre, Biola M. Grassi, Luigi Kreuzhuber, Roman Ruklisa, Dace Rosa, Isabel M. Tomé, Ana R. Elding, Heather van Geffen, Johanna P. Jiang, Tao Farrow, Samantha Cairns, Jonathan Al-Subaie, Abeer M. Ashford, Sofie Attwood, Antony Batista, Joana Bouman, Heleen Burden, Frances Choudry, Fizzah A. Clarke, Laura Flicek, Paul Garner, Stephen F. Haimel, Matthias Kempster, Carly Ladopoulos, Vasileios Lenaerts, An-Sofie Materek, Paulina M. McKinney, Harriet Meacham, Stuart Mead, Daniel Nagy, Magdolna Penkett, Christopher J. Rendon, Augusto Seyres, Denis Sun, Benjamin Tuna, Salih van der Weide, Marie-Elise Wingett, Steven W. Martens, Joost H. Stegle, Oliver Richardson, Sylvia Vallier, Ludovic Roberts, David J. Freson, Kathleen Wernisch, Lorenz Stunnenberg, Hendrik G. Danesh, John Fraser, Peter Soranzo, Nicole Butterworth, Adam S. Heemskerk, Johan W. Turro, Ernest Spivakov, Mikhail Ouwehand, Willem H. Astle, William J. Downes, Kate Kostadima, Myrto Frontini, Mattia |
| author_sort | Petersen, Romina |
| collection | PubMed |
| description | Linking non-coding genetic variants associated with the risk of diseases or disease-relevant traits to target genes is a crucial step to realize GWAS potential in the introduction of precision medicine. Here we set out to determine the mechanisms underpinning variant association with platelet quantitative traits using cell type-matched epigenomic data and promoter long-range interactions. We identify potential regulatory functions for 423 of 565 (75%) non-coding variants associated with platelet traits and we demonstrate, through ex vivo and proof of principle genome editing validation, that variants in super enhancers play an important role in controlling archetypical platelet functions. |
| format | Online Article Text |
| id | pubmed-5511350 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2017 |
| publisher | Nature Publishing Group |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-55113502017-07-20 Platelet function is modified by common sequence variation in megakaryocyte super enhancers Petersen, Romina Lambourne, John J. Javierre, Biola M. Grassi, Luigi Kreuzhuber, Roman Ruklisa, Dace Rosa, Isabel M. Tomé, Ana R. Elding, Heather van Geffen, Johanna P. Jiang, Tao Farrow, Samantha Cairns, Jonathan Al-Subaie, Abeer M. Ashford, Sofie Attwood, Antony Batista, Joana Bouman, Heleen Burden, Frances Choudry, Fizzah A. Clarke, Laura Flicek, Paul Garner, Stephen F. Haimel, Matthias Kempster, Carly Ladopoulos, Vasileios Lenaerts, An-Sofie Materek, Paulina M. McKinney, Harriet Meacham, Stuart Mead, Daniel Nagy, Magdolna Penkett, Christopher J. Rendon, Augusto Seyres, Denis Sun, Benjamin Tuna, Salih van der Weide, Marie-Elise Wingett, Steven W. Martens, Joost H. Stegle, Oliver Richardson, Sylvia Vallier, Ludovic Roberts, David J. Freson, Kathleen Wernisch, Lorenz Stunnenberg, Hendrik G. Danesh, John Fraser, Peter Soranzo, Nicole Butterworth, Adam S. Heemskerk, Johan W. Turro, Ernest Spivakov, Mikhail Ouwehand, Willem H. Astle, William J. Downes, Kate Kostadima, Myrto Frontini, Mattia Nat Commun Article Linking non-coding genetic variants associated with the risk of diseases or disease-relevant traits to target genes is a crucial step to realize GWAS potential in the introduction of precision medicine. Here we set out to determine the mechanisms underpinning variant association with platelet quantitative traits using cell type-matched epigenomic data and promoter long-range interactions. We identify potential regulatory functions for 423 of 565 (75%) non-coding variants associated with platelet traits and we demonstrate, through ex vivo and proof of principle genome editing validation, that variants in super enhancers play an important role in controlling archetypical platelet functions. Nature Publishing Group 2017-07-13 /pmc/articles/PMC5511350/ /pubmed/28703137 http://dx.doi.org/10.1038/ncomms16058 Text en Copyright © 2017, The Author(s) http://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/ |
| spellingShingle | Article Petersen, Romina Lambourne, John J. Javierre, Biola M. Grassi, Luigi Kreuzhuber, Roman Ruklisa, Dace Rosa, Isabel M. Tomé, Ana R. Elding, Heather van Geffen, Johanna P. Jiang, Tao Farrow, Samantha Cairns, Jonathan Al-Subaie, Abeer M. Ashford, Sofie Attwood, Antony Batista, Joana Bouman, Heleen Burden, Frances Choudry, Fizzah A. Clarke, Laura Flicek, Paul Garner, Stephen F. Haimel, Matthias Kempster, Carly Ladopoulos, Vasileios Lenaerts, An-Sofie Materek, Paulina M. McKinney, Harriet Meacham, Stuart Mead, Daniel Nagy, Magdolna Penkett, Christopher J. Rendon, Augusto Seyres, Denis Sun, Benjamin Tuna, Salih van der Weide, Marie-Elise Wingett, Steven W. Martens, Joost H. Stegle, Oliver Richardson, Sylvia Vallier, Ludovic Roberts, David J. Freson, Kathleen Wernisch, Lorenz Stunnenberg, Hendrik G. Danesh, John Fraser, Peter Soranzo, Nicole Butterworth, Adam S. Heemskerk, Johan W. Turro, Ernest Spivakov, Mikhail Ouwehand, Willem H. Astle, William J. Downes, Kate Kostadima, Myrto Frontini, Mattia Platelet function is modified by common sequence variation in megakaryocyte super enhancers |
| title | Platelet function is modified by common sequence variation in megakaryocyte super enhancers |
| title_full | Platelet function is modified by common sequence variation in megakaryocyte super enhancers |
| title_fullStr | Platelet function is modified by common sequence variation in megakaryocyte super enhancers |
| title_full_unstemmed | Platelet function is modified by common sequence variation in megakaryocyte super enhancers |
| title_short | Platelet function is modified by common sequence variation in megakaryocyte super enhancers |
| title_sort | platelet function is modified by common sequence variation in megakaryocyte super enhancers |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5511350/ https://www.ncbi.nlm.nih.gov/pubmed/28703137 http://dx.doi.org/10.1038/ncomms16058 |
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