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

© 2018, The Author(s). 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,...

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Main Author: Moses, Eric
Format: Journal Article
Published: Macmillan Publishers Limited 2018
Online Access:http://hdl.handle.net/20.500.11937/71635
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author Moses, Eric
author_facet Moses, Eric
author_sort Moses, Eric
building Curtin Institutional Repository
collection Online Access
description © 2018, The Author(s). 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.
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spelling curtin-20.500.11937-716352019-03-18T04:35:28Z Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways Moses, Eric © 2018, The Author(s). 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. 2018 Journal Article http://hdl.handle.net/20.500.11937/71635 10.1038/s41467-018-06649-5 http://creativecommons.org/licenses/by/4.0/ Macmillan Publishers Limited fulltext
spellingShingle Moses, Eric
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
url http://hdl.handle.net/20.500.11937/71635