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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.; [...]

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

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  • Medientyp: E-Artikel
  • Titel: Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways
  • Beteiligte: 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.; [...]
  • Erschienen: Springer Science and Business Media LLC, 2018
  • Erschienen in: Nature Communications
  • Sprache: Englisch
  • DOI: 10.1038/s41467-018-06649-5
  • ISSN: 2041-1723
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>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 <jats:italic>MTAP</jats:italic>, <jats:italic>PLA2G6</jats:italic>, and <jats:italic>IRF4</jats:italic>, and detect novel SNPs in <jats:italic>KITLG</jats:italic> 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 <jats:italic>GPRC5A, CYP1B1</jats:italic>, <jats:italic>PPARGC1B</jats:italic>, <jats:italic>HDAC4</jats:italic>, <jats:italic>FAM208B, DOCK8</jats:italic>, and <jats:italic>SYNE2</jats:italic> reached global significance, and other loci, including <jats:italic>MIR146A</jats:italic> and <jats:italic>OBFC1,</jats:italic> reached a suggestive level. Overall, we conclude that most nevus genes affect melanoma risk (<jats:italic>KITLG</jats:italic> an exception), while many melanoma risk loci do not alter nevus count. For example, variants in <jats:italic>TERC</jats:italic> and <jats:italic>OBFC1</jats:italic> affect both traits, but other telomere length maintenance genes seem to affect melanoma risk only. Our findings implicate multiple pathways in nevogenesis.</jats:p>
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