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

Research output: Contribution to journalArticle


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.


External organisations
  • University of Leeds
  • National Cancer Institute, NCI
  • National and Kapodistrian University of Athens
  • University of Genoa
  • Maurizio Bufalini Hospital
  • University of L'Aquila
  • New South Wales Health Pathology, Sydney, New South Wales, Australia.
  • Ospedale Policlinico San Martino
  • University of Michigan
  • Instituto Valenciano de Oncologia
  • Istituto Nazionale dei Tumori
  • University of Dundee
  • University of Florence
  • Princess Alexandra Hospital
  • Haukeland University Hospital
  • Dartmouth College
  • Paris Descartes University
  • Tel-Aviv University
  • University of Queensland
  • University of Tasmania
  • Veneto Institute of Oncology
  • National Institutes of Health, United States
  • QIMR Berghofer Medical Research Institute
  • University of Valencia
  • University of Barcelona
  • Cyprus Institute of Neurology and Genetics
  • Andreas Syggros Hospital
  • Biomedical Network on Rare Diseases (CIBERER)
  • Istituto Nazionale Tumori IRCCS - Fondazione G Pascale, Napoli
  • University of Bergamo
  • University of Oslo
  • NHS Trust Herts
  • Catholic University School of Medicine
  • Azienda Ospedaliera Papa Giovanni XXIII
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical Genetics
  • Cancer and Oncology
Original languageEnglish
JournalNature Genetics
Publication statusE-pub ahead of print - 2020 Apr 27
Publication categoryResearch