High melanocytic nevus count is a strong predictor of melanoma risk. A GWAS of nevus
count in Australian adolescent twins identified an association of nevus count with
the interferon regulatory factor 4 gene (IRF4 [p = 6 x 10(-9)]). There was a strong
genotype-by-age interaction, which was replicated in independent UK samples of adolescents
and adults. The rs12203592(*)T allele was associated with high nevus counts and high
freckling scores in adolescents, but with low nevus counts and high freckling scores
in adults. The rs12203592(*)T increased counts of flat (compound and junctional) nevi
in Australian adolescent twins, but decreased counts of raised (intradermal) nevi.
In combined analysis of melanoma case-control data from Australia, the UK, and Sweden,
the rs12203592(*)C allele was associated with melanoma (odds ratio [OR] 1.15, p =
4 x 10(-3)), most significantly on the trunk (OR = 1.33, p = 2.5 x 10(-5)). The melanoma
association was corroborated in a GWAS performed by the GenoMEL consortium for an
adjacent SNP, rs872071 (rs872071(*)T: OR 1.14, p = 0.0035; excluding Australian, the
UK, and Swedish samples typed at rs12203592: OR 1.08, p = 0.08).
Copyright 2010 The American Society of Human Genetics. Published by Elsevier Inc.
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