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Journal Articles International Journal of Cancer Year : 2014

Fine mapping of genetic susceptibility loci for melanoma reveals a mixture of single variant and multiple variant regions

John C Taylor
  • Function : Author
Mark Harland
  • Function : Author
Marie‐françoise Avril
  • Function : Author
Esther Azizi
  • Function : Author
Giovanna Bianchi Scarrà
  • Function : Author
Tadeusz Dębniak
  • Function : Author
Per Helsing
  • Function : Author
Christian Ingvar
  • Function : Author
Julie Lang
  • Function : Author
Jan Lubiński
  • Function : Author
Rona M Mackie
  • Function : Author
Srdjan Novaković
  • Function : Author
Håkan Olsson
  • Function : Author
Joan Anton Puig‐butille
  • Function : Author
Wilbert van Workum
  • Function : Author
Peter A Kanetsky
  • Function : Author
Paul D P Pharoah
  • Function : Author
Julia A Newton Bishop
  • Function : Author
D. Timothy Bishop
  • Function : Author
Mark M Iles
  • Function : Author

Abstract

At least 17 genomic regions are established as harboring melanoma susceptibility variants, in most instances with genome‐wide levels of significance and replication in independent samples. Based on genome‐wide single nucleotide polymorphism (SNP) data augmented by imputation to the 1,000 Genomes reference panel, we have fine mapped these regions in over 5,000 individuals with melanoma (mainly from the GenoMEL consortium) and over 7,000 ethnically matched controls. A penalized regression approach was used to discover those SNP markers that most parsimoniously explain the observed association in each genomic region. For the majority of the regions, the signal is best explained by a single SNP, which sometimes, as in the tyrosinase region, is a known functional variant. However in five regions the explanation is more complex. At the CDKN2A locus, for example, there is strong evidence that not only multiple SNPs but also multiple genes are involved. Our results illustrate the variability in the biology underlying genome‐wide susceptibility loci and make steps toward accounting for some of the “missing heritability.”
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cea-04580612 , version 1 (20-05-2024)

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Jennifer H Barrett, John C Taylor, Chloe Bright, Mark Harland, Alison M Dunning, et al.. Fine mapping of genetic susceptibility loci for melanoma reveals a mixture of single variant and multiple variant regions. International Journal of Cancer, 2014, 136 (6), pp.1351 - 1360. ⟨10.1002/ijc.29099⟩. ⟨cea-04580612⟩
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