Genome-wide association meta-analyses combining multiple risk phenotypes provide insights into the genetic architecture of cutaneous melanoma susceptibility

AMFS Investigators, MelaNostrum Consortium, GenoMEL Consortium, Q-MEGA and QTWIN Investigators, ATHENS Melanoma Study Group, 23andMe, The SDH Study Group, IBD Investigators, Essen-Heidelberg Investigators

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Most genetic susceptibility to cutaneous melanoma remains to be discovered. Meta-analysis genome-wide association study (GWAS) of 36,760 cases of melanoma (67% newly genotyped) and 375,188 controls identified 54 significant (P < 5 × 10−8) loci with 68 independent single nucleotide polymorphisms. Analysis of risk estimates across geographical regions and host factors suggests the acral melanoma subtype is uniquely unrelated to pigmentation. Combining this meta-analysis with GWAS of nevus count and hair color, and transcriptome association approaches, uncovered 31 potential secondary loci for a total of 85 cutaneous melanoma susceptibility loci. These findings provide insights into cutaneous melanoma genetic architecture, reinforcing the importance of nevogenesis, pigmentation and telomere maintenance, together with identifying potential new pathways for cutaneous melanoma pathogenesis.

Original languageEnglish (US)
Pages (from-to)494-504
Number of pages11
JournalNature genetics
Volume52
Issue number5
DOIs
StatePublished - May 1 2020

ASJC Scopus subject areas

  • Genetics

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    AMFS Investigators, MelaNostrum Consortium, GenoMEL Consortium, Q-MEGA and QTWIN Investigators, ATHENS Melanoma Study Group, 23andMe, The SDH Study Group, IBD Investigators, & Essen-Heidelberg Investigators (2020). Genome-wide association meta-analyses combining multiple risk phenotypes provide insights into the genetic architecture of cutaneous melanoma susceptibility. Nature genetics, 52(5), 494-504. https://doi.org/10.1038/s41588-020-0611-8