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Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways
The total number of acquired melanocytic nevi on the skin is strongly correlated with melanoma risk. Here we report a meta-analysis of 11 nevus GWAS from Australia, Netherlands, UK, and USA comprising 52,506 individuals. We confirm known loci including MTAP, PLA2G6, and IRF4, and detect novel SNPs i...
| 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/PMC6235897/ https://www.ncbi.nlm.nih.gov/pubmed/30429480 http://dx.doi.org/10.1038/s41467-018-06649-5 |
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| author | Duffy, David L. Zhu, Gu Li, Xin Sanna, Marianna Iles, Mark M. Jacobs, Leonie C. Evans, David M. Yazar, Seyhan Beesley, Jonathan Law, Matthew H. Kraft, Peter Visconti, Alessia Taylor, John C. Liu, Fan Wright, Margaret J. Henders, Anjali K. Bowdler, Lisa Glass, Dan Ikram, M. Arfan Uitterlinden, André G. Madden, Pamela A. Heath, Andrew C. Nelson, Elliot C. Green, Adele C. Chanock, Stephen Barrett, Jennifer H. Brown, Matthew A. Hayward, Nicholas K. MacGregor, Stuart Sturm, Richard A. Hewitt, Alex W. Kayser, Manfred Hunter, David J. Newton Bishop, Julia A. Spector, Timothy D. Montgomery, Grant W. Mackey, David A. Smith, George Davey Nijsten, Tamar E. Bishop, D. Timothy Bataille, Veronique Falchi, Mario Han, Jiali Martin, Nicholas G. |
| author_facet | Duffy, David L. Zhu, Gu Li, Xin Sanna, Marianna Iles, Mark M. Jacobs, Leonie C. Evans, David M. Yazar, Seyhan Beesley, Jonathan Law, Matthew H. Kraft, Peter Visconti, Alessia Taylor, John C. Liu, Fan Wright, Margaret J. Henders, Anjali K. Bowdler, Lisa Glass, Dan Ikram, M. Arfan Uitterlinden, André G. Madden, Pamela A. Heath, Andrew C. Nelson, Elliot C. Green, Adele C. Chanock, Stephen Barrett, Jennifer H. Brown, Matthew A. Hayward, Nicholas K. MacGregor, Stuart Sturm, Richard A. Hewitt, Alex W. Kayser, Manfred Hunter, David J. Newton Bishop, Julia A. Spector, Timothy D. Montgomery, Grant W. Mackey, David A. Smith, George Davey Nijsten, Tamar E. Bishop, D. Timothy Bataille, Veronique Falchi, Mario Han, Jiali Martin, Nicholas G. |
| author_sort | Duffy, David L. |
| collection | PubMed |
| description | The total number of acquired melanocytic nevi on the skin is strongly correlated with melanoma risk. Here we report a meta-analysis of 11 nevus GWAS from Australia, Netherlands, UK, and USA comprising 52,506 individuals. We confirm known loci including MTAP, PLA2G6, and IRF4, and detect novel SNPs in KITLG and a region of 9q32. In a bivariate analysis combining the nevus results with a recent melanoma GWAS meta-analysis (12,874 cases, 23,203 controls), SNPs near GPRC5A, CYP1B1, PPARGC1B, HDAC4, FAM208B, DOCK8, and SYNE2 reached global significance, and other loci, including MIR146A and OBFC1, reached a suggestive level. Overall, we conclude that most nevus genes affect melanoma risk (KITLG an exception), while many melanoma risk loci do not alter nevus count. For example, variants in TERC and OBFC1 affect both traits, but other telomere length maintenance genes seem to affect melanoma risk only. Our findings implicate multiple pathways in nevogenesis. |
| format | Online Article Text |
| id | pubmed-6235897 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2018 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-62358972018-11-16 Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways Duffy, David L. Zhu, Gu Li, Xin Sanna, Marianna Iles, Mark M. Jacobs, Leonie C. Evans, David M. Yazar, Seyhan Beesley, Jonathan Law, Matthew H. Kraft, Peter Visconti, Alessia Taylor, John C. Liu, Fan Wright, Margaret J. Henders, Anjali K. Bowdler, Lisa Glass, Dan Ikram, M. Arfan Uitterlinden, André G. Madden, Pamela A. Heath, Andrew C. Nelson, Elliot C. Green, Adele C. Chanock, Stephen Barrett, Jennifer H. Brown, Matthew A. Hayward, Nicholas K. MacGregor, Stuart Sturm, Richard A. Hewitt, Alex W. Kayser, Manfred Hunter, David J. Newton Bishop, Julia A. Spector, Timothy D. Montgomery, Grant W. Mackey, David A. Smith, George Davey Nijsten, Tamar E. Bishop, D. Timothy Bataille, Veronique Falchi, Mario Han, Jiali Martin, Nicholas G. Nat Commun Article The total number of acquired melanocytic nevi on the skin is strongly correlated with melanoma risk. Here we report a meta-analysis of 11 nevus GWAS from Australia, Netherlands, UK, and USA comprising 52,506 individuals. We confirm known loci including MTAP, PLA2G6, and IRF4, and detect novel SNPs in KITLG and a region of 9q32. In a bivariate analysis combining the nevus results with a recent melanoma GWAS meta-analysis (12,874 cases, 23,203 controls), SNPs near GPRC5A, CYP1B1, PPARGC1B, HDAC4, FAM208B, DOCK8, and SYNE2 reached global significance, and other loci, including MIR146A and OBFC1, reached a suggestive level. Overall, we conclude that most nevus genes affect melanoma risk (KITLG an exception), while many melanoma risk loci do not alter nevus count. For example, variants in TERC and OBFC1 affect both traits, but other telomere length maintenance genes seem to affect melanoma risk only. Our findings implicate multiple pathways in nevogenesis. Nature Publishing Group UK 2018-11-14 /pmc/articles/PMC6235897/ /pubmed/30429480 http://dx.doi.org/10.1038/s41467-018-06649-5 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 Duffy, David L. Zhu, Gu Li, Xin Sanna, Marianna Iles, Mark M. Jacobs, Leonie C. Evans, David M. Yazar, Seyhan Beesley, Jonathan Law, Matthew H. Kraft, Peter Visconti, Alessia Taylor, John C. Liu, Fan Wright, Margaret J. Henders, Anjali K. Bowdler, Lisa Glass, Dan Ikram, M. Arfan Uitterlinden, André G. Madden, Pamela A. Heath, Andrew C. Nelson, Elliot C. Green, Adele C. Chanock, Stephen Barrett, Jennifer H. Brown, Matthew A. Hayward, Nicholas K. MacGregor, Stuart Sturm, Richard A. Hewitt, Alex W. Kayser, Manfred Hunter, David J. Newton Bishop, Julia A. Spector, Timothy D. Montgomery, Grant W. Mackey, David A. Smith, George Davey Nijsten, Tamar E. Bishop, D. Timothy Bataille, Veronique Falchi, Mario Han, Jiali Martin, Nicholas G. Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways |
| title | Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways |
| title_full | Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways |
| title_fullStr | Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways |
| title_full_unstemmed | Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways |
| title_short | Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways |
| title_sort | novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6235897/ https://www.ncbi.nlm.nih.gov/pubmed/30429480 http://dx.doi.org/10.1038/s41467-018-06649-5 |
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