Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1038/s41467-018-06649-5

Type

Journal article

Journal

Nat Commun

Publication Date

14/11/2018

Volume

9

Keywords

Carrier Proteins, Cytochrome P-450 CYP1B1, European Continental Ancestry Group, Genetic Pleiotropy, Genetic Predisposition to Disease, Genome-Wide Association Study, Group VI Phospholipases A2, Guanine Nucleotide Exchange Factors, Histone Deacetylases, Humans, Interferon Regulatory Factors, Melanoma, MicroRNAs, Microfilament Proteins, Nerve Tissue Proteins, Nevus, Pigmented, Nuclear Proteins, Polymorphism, Single Nucleotide, RNA, RNA-Binding Proteins, Receptors, G-Protein-Coupled, Repressor Proteins, Skin Neoplasms, Stem Cell Factor, Telomerase, Telomere-Binding Proteins