Title |
IRF4 Variants Have Age-Specific Effects on Nevus Count and Predispose to Melanoma
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Published in |
American Journal of Human Genetics, June 2010
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DOI | 10.1016/j.ajhg.2010.05.017 |
Pubmed ID | |
Authors |
David L. Duffy, Mark M. Iles, Dan Glass, Gu Zhu, Jennifer H. Barrett, Veronica Höiom, Zhen Z. Zhao, Richard A. Sturm, Nicole Soranzo, Chris Hammond, Marina Kvaskoff, David C. Whiteman, Massimo Mangino, Johan Hansson, Julia A. Newton-Bishop, GenoMEL, Veronique Bataille, Nicholas K. Hayward, Nicholas G. Martin, D. Timothy Bishop, Timothy D. Spector, Grant W. Montgomery |
Abstract |
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). |
X Demographics
Geographical breakdown
Country | Count | As % |
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Unknown | 1 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Brazil | 2 | 3% |
Australia | 1 | 1% |
Turkey | 1 | 1% |
Unknown | 65 | 94% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 13 | 19% |
Student > Master | 12 | 17% |
Student > Ph. D. Student | 10 | 14% |
Professor | 6 | 9% |
Student > Bachelor | 5 | 7% |
Other | 13 | 19% |
Unknown | 10 | 14% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 25 | 36% |
Biochemistry, Genetics and Molecular Biology | 17 | 25% |
Medicine and Dentistry | 14 | 20% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 1% |
Unspecified | 1 | 1% |
Other | 2 | 3% |
Unknown | 9 | 13% |