Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

David L. Duffy, Gu Zhu, Xin Li, Marianna Sanna, Mark M. Iles, Leonie C. Jacobs, David M. Evans, Seyhan Yazar, Jonathan Beesley, Matthew H. Law, Peter Kraft, Alessia Visconti, John C. Taylor, Fan Liu, Margaret J. Wright, Anjali K. Henders, Lisa Bowdler, Dan Glass, M. Arfan Ikram, André G. Uitterlinden, Pamela A. Madden, Andrew C. Heath, Elliot C. Nelson, Adele C. Green, Stephen Chanock, Jennifer H. Barrett, Matthew A. Brown, Nicholas K. Hayward, Stuart MacGregor, Richard A. Sturm, Alex W. Hewitt, Manfred Kayser, David J. Hunter, Julia A. Newton Bishop, Timothy D. Spector, Grant W. Montgomery, David A. Mackey, George Davey Smith, Tamar E. Nijsten, D. Timothy Bishop, Veronique Bataille, Mario Falchi, Jiali Han, Nicholas G. Martin

ABSTRACT

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. More... »

PAGES

4774

References to SciGraph publications

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    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-018-06649-5

    DOI

    http://dx.doi.org/10.1038/s41467-018-06649-5

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1109832824

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30429480


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