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


Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Amos, CI; Wang, L-E; Lee, JE; Gershenwald, JE; Chen, WV; Fang, S; Kosoy, R; Zhang, M; Qureshi, AA; Vattathil, S; Schacherer, CW; Gardner, JM; Wang, Y; Bishop, DT; Barrett, JH; GenoMEL Investigators, ; MacGregor, S; Hayward, NK; Martin, NG; Duffy, DL; Q-Mega Investigators, ; Mann, GJ; Cust, A; Hopper, J; AMFS Investigators, ; Brown, KM; Grimm, EA; Xu, Y; Han, Y; Jing, K; McHugh, C; Laurie, CC; Doheny, KF; Pugh, EW; Seldin, MF; Han, J; Wei, Q

Published Date

  • December 15, 2011

Published In

Volume / Issue

  • 20 / 24

Start / End Page

  • 5012 - 5023

PubMed ID

  • 21926416

Pubmed Central ID

  • 21926416

Electronic International Standard Serial Number (EISSN)

  • 1460-2083

Digital Object Identifier (DOI)

  • 10.1093/hmg/ddr415


  • eng

Conference Location

  • England