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

Melanoma GWAS Consortium

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish (US)
Article number4774
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

Fingerprint

Nevi and Melanomas
loci
Nevus
Melanoma
genes
Genome-Wide Association Study
bivariate analysis
Genes
telomeres
Single Nucleotide Polymorphism
Meta-Analysis
Telomere Homeostasis
Netherlands
Pigmented Nevus
maintenance
Skin

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways. / Melanoma GWAS Consortium.

In: Nature Communications, Vol. 9, No. 1, 4774, 01.12.2018.

Research output: Contribution to journalArticle

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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.",
author = "{Melanoma GWAS Consortium} and Duffy, {David L.} and Gu Zhu and Xin Li and Marianna Sanna and Iles, {Mark M.} and Jacobs, {Leonie C.} and Evans, {David M.} and Seyhan Yazar and Jonathan Beesley and Law, {Matthew H.} and Peter Kraft and Alessia Visconti and Taylor, {John C.} and Fan Lui and Wright, {Margaret J.} and Henders, {Anjali K.} and Lisa Bowdler and Dan Glass and Ikram, {Arfan M.} and Uitterlinden, {Andr{\'e} G.} and Madden, {Pamela A.} and Heath, {Andrew C.} and Nelson, {Elliot C.} and Green, {Adele C.} and Stephen Chanock and Barrett, {Jennifer H.} and Brown, {Matthew A.} and Hayward, {Nicholas K.} and Stuart MacGregor and Sturm, {Richard A.} and Hewitt, {Alex W.} and Lee, {Jeffrey E.} and Myriam Brossard and Moses, {Eric K.} and Fengju Song and Rajiv Kumar and Easton, {Douglas F.} and Pharoah, {Paul D.P.} and Swerdlow, {Anthony J.} and Kypreou, {Katerina P.} and Mark Harland and Juliette Randerson-Moor and Akslen, {Lars A.} and Andresen, {Per A.} and Avril, {Marie Fran{\cc}oise} and Esther Azizi and Scarr{\`a}, {Giovanna Bianchi} and Brown, {Kevin M.} and Tadeusz Dębniak and Jiali Han",
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