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

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.

SUBMITTER: Duffy DL

PROVIDER: S-EPMC6235897 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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

Duffy David L DL Zhu Gu G Li Xin X Sanna Marianna M Iles Mark M MM Jacobs Leonie C LC Evans David M DM Yazar Seyhan S Beesley Jonathan J Law Matthew H MH Kraft Peter P Visconti Alessia A Taylor John C JC Liu Fan F Wright Margaret J MJ Henders Anjali K AK Bowdler Lisa L Glass Dan D Ikram M Arfan MA Uitterlinden André G AG Madden Pamela A PA Heath Andrew C AC Nelson Elliot C EC Green Adele C AC Chanock Stephen S Barrett Jennifer H JH Brown Matthew A MA Hayward Nicholas K NK MacGregor Stuart S Sturm Richard A RA Hewitt Alex W AW Kayser Manfred M Hunter David J DJ Newton Bishop Julia A JA Spector Timothy D TD Montgomery Grant W GW Mackey David A DA Smith George Davey GD Nijsten Tamar E TE Bishop D Timothy DT Bataille Veronique V Falchi Mario M Han Jiali J Martin Nicholas G NG

Nature communications 20181114 1

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, ...[more]

PMID: 30429480

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

Publications

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

Similar Datasets

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