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

Research output: Contribution to journalArticle

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

Original languageEnglish
JournalNature Genetics
DOIs
Publication statusAccepted/In press - 1 Jan 2020

King's Authors

  • 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

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.

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