Genome-wide association study identifies novel loci predisposing to cutaneous melanoma

Christopher I. Amos, Li E. Wang, Jeffrey E. Lee, Jeffrey E. Gershenwald, Wei V. Chen, Shenying Fang, Roman Kosoy, Mingfeng Zhang, Abrar A. Qureshi, Selina Vattathil, Christopher W. Schacherer, Julie M. Gardner, Yuling Wang, D. Tim bishop, Jennifer H. Barrett, Stuart Macgregor, Nicholas K. Hayward, Nicholas G. Martin, David L. Duffy, Graham J. MannAnne Cust, John Hopper, Kevin M. Brown, Elizabeth A. Grimm, Yaji Xu, Younghun Han, Kaiyan Jing, Caitlin Mchugh, Cathy C. Laurie, Kim F. Doheny, Elizabeth W. Pugh, Michael F. Seldin, Jiali Han, Qingyi Wei, Joanne F. Aitken, Bruce K. Armstrong, Graham G. Giles, Richard F. Kefford, Mark A. Jenkins, Helen Schmid, Paula Aguilera, Celia Badenas, Cristina Carrera, Francisco Cuellar, Daniel Gabriel, Estefania Martinez, Melinda Gonzalez, Pablo Iglesias, Josep Malvehy, Rosa Marti-Laborda, Montse Mila, Zighe Ogbah, Joan Anton Puig Butille, Susana Puig, Llúcia Alós, Ana Arance, Pedro Arguís, Antonio Campo, Teresa Castel, Carlos Conill, Jose Palou, Ramon Rull, Marcelo Sánchez, Sergi Vidal-Sicart, Antonio Vilalta, Ramon Vilella, Grant W. Montgomery, David L. Duffy, David C. Whiteman

Research output: Contribution to journalArticlepeer-review

157 Citations (Scopus)


We performed a multistage genome-wide association study of melanoma. In a discovery cohort of 1804 melanoma cases and 1026 controls, we identified loci at chromosomes 15q13.1 (HERC2/OCA2 region) and 16q24.3 (MC1R) regions that reached genome-wide significance within this study and also found strong evidence for genetic effects on susceptibility to melanoma from markers on chromosome 9p21.3 in the p16/ARF region and on chromosome 1q21.3 (ARNT/LASS2/ANXA9 region). The most significant single-nucleotide polymorphisms (SNPs) in the 15q13.1 locus (rs1129038 and rs12913832) lie within a genomic region that has profound effects on eye and skin color; notably, 50% of variability in eye color is associated with variation in the SNP rs12913832. Because eye and skin colors vary across European populations, we further evaluated the associations of the significant SNPs after carefully adjusting for European substructure. We also evaluated the top 10 most significant SNPs by using data from three other genome-wide scans. Additional in silico data provided replication of the findings from the most significant region on chromosome 1q21.3 rs7412746 (P = 6 × 10-10). Together, these data identified several candidate genes for additional studies to identify causal variants predisposing to increased risk for developing melanoma.

Original languageEnglish
Pages (from-to)5012-5023
Number of pages12
JournalHuman Molecular Genetics
Issue number24
Publication statusPublished - 1 Dec 2011
Externally publishedYes


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