Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways.
Green, Adèle C
Newton, Bishop JA
AffiliationQIMR Berghofer Medical Research Institute, Brisbane, Australia.
MetadataShow full item record
AbstractThe 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.
CitationDuffy DL, Zhu G, Li X, Sanna M, Iles MM, Jacobs LC, et al. Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways. Nat Commun. 2018 Nov 14;9(1):4774.
- Polymorphisms in nevus-associated genes MTAP, PLA2G6, and IRF4 and the risk of invasive cutaneous melanoma.
- Authors: Kvaskoff M, Whiteman DC, Zhao ZZ, Montgomery GW, Martin NG, Hayward NK, Duffy DL
- Issue date: 2011 Oct
- Two-stage genome-wide association study identifies a novel susceptibility locus associated with melanoma.
- Authors: Ransohoff KJ, Wu W, Cho HG, Chahal HC, Lin Y, Dai HJ, Amos CI, Lee JE, Tang JY, Hinds DA, Han J, Wei Q, Sarin KY
- Issue date: 2017 Mar 14
- Genetic factors associated with naevus count and dermoscopic patterns: preliminary results from the Study of Nevi in Children (SONIC).
- Authors: Orlow I, Satagopan JM, Berwick M, Enriquez HL, White KA, Cheung K, Dusza SW, Oliveria SA, Marchetti MA, Scope A, Marghoob AA, Halpern AC
- Issue date: 2015 Apr
- IRF4 variants have age-specific effects on nevus count and predispose to melanoma.
- Authors: Duffy DL, Iles MM, Glass D, Zhu G, Barrett JH, Höiom V, Zhao ZZ, Sturm RA, Soranzo N, Hammond C, Kvaskoff M, Whiteman DC, Mangino M, Hansson J, Newton-Bishop JA, GenoMEL., Bataille V, Hayward NK, Martin NG, Bishop DT, Spector TD, Montgomery GW
- Issue date: 2010 Jul 9
- No association between telomere length-related loci and number of cutaneous nevi.
- Authors: Li X, Liang G, Du M, De Vivo I, Nan H
- Issue date: 2016 Dec 13