Genome-wide association study identifies variants at 9p21 and 22q13 associated with development of cutaneous nevi

Mario Falchi, Veronique Bataille, Nicholas K Hayward, David L Duffy, Julia A Newton Bishop, Tomi Pastinen, Alessandra Cervino, Zhen Z Zhao, Panos Deloukas, Nicole Soranzo, David E Elder, Jennifer H Barrett, Nicholas G Martin, D Timothy Bishop, Grant W Montgomery, Timothy D Spector

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184 Citations (Scopus)

Abstract

A high melanocytic nevi count is the strongest known risk factor for cutaneous melanoma. We conducted a genome-wide association study for nevus count using 297,108 SNPs in 1,524 twins, with validation in an independent cohort of 4,107 individuals. We identified strongly associated variants in MTAP, a gene adjacent to the familial melanoma susceptibility locus CDKN2A on 9p21 (rs4636294, combined P = 3.4 x 10(-15)), as well as in PLA2G6 on 22q13.1 (rs2284063, combined P = 3.4 x 10(-8)). In addition, variants in these two loci showed association with melanoma risk in 3,131 melanoma cases from two independent studies, including rs10757257 at 9p21, combined P = 3.4 x 10(-8), OR = 1.23 (95% CI = 1.15-1.30) and rs132985 at 22q13.1, combined P = 2.6 x 10(-7), OR = 1.23 (95% CI = 1.15-1.30). This provides the first report of common variants associated to nevus number and demonstrates association of these variants with melanoma susceptibility.
Original languageEnglish
Pages (from-to)915 - 919
Number of pages5
JournalNature Genetics
Volume41
Issue number8
DOIs
Publication statusPublished - Aug 2009

Keywords

  • Alleles
  • Chromosomes, Human, Pair 22
  • Chromosomes, Human, Pair 9
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Great Britain
  • Homozygote
  • Humans
  • Melanoma
  • Nevus
  • Polymorphism, Single Nucleotide
  • Precancerous Conditions
  • Skin Neoplasms

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