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Genome-wide association meta-analyses combining multiple risk phenotypes provide insights into the genetic architecture of cutaneous melanoma susceptibility

journal contribution
posted on 2023-05-20, 23:56 authored by Landi, MT, Bishop, DT, MacGregor, S, Machiela, MJ, Stratigos, AJ, Ghiorzo, P, Brossard, M, Calista, D, Choi, J, Fargnoli, MC, Zhang, T, Rodolfo, M, Trower, AJ, Menin, C, Martinez, J, Hadjisavvas, A, Song, L, Stefanaki, I, Scolyer, R, Yang, R, Goldstein, AM, Potrony, M, Kypreou, KP, Pastorino, L, Queirolo, P, Pellegrini, C, Cattaneo, L, Zawistowski, M, Gimenez-Xavier, P, Rodriguez, A, Elefanti, L, Manoukian, S, Rivoltini, L, Smith, BH, Loizidou, MA, Del Regno, L, Massi, D, Mandala, M, Khosrotehrani, K, Akslen, LA, Amos, CI, Andresen, PA, Avril, MF, Azizi, E, Soyer, HP, Bataille, V, Dalmasso, B, Bowdler, LM, Kathryn BurdonKathryn Burdon, Chen, WV, Codd, V, Craig, JE, Debniak, T, Falchi, M, Fang, S, Friedman, E, Simi, S, Galan, P, Garcia-Casado, Z, Gillanders, EM, Gordon, S, Green, A, Gruis, NA, Hansson, J, Harland, M, Harris, J, Helsing, P, Henders, A, Hocevar, M, Hoiom, V, Hunter, D, Ingvar, C, Kumar, R, Lang, J, Lathrop, GM, Lee, JE, Li, X, Lubinski, J, Mackie, RM, Malt, M, Malvehy, J, McAloney, K, Mohamdi, H, Molven, A, Eric MosesEric Moses, Neale, RE, Novakovic, S, Nyholt, DR, Olsson, H, Orr, N, Fritsche, LG, Puig-Butille, JA, Qureshi, AA, Radford-Smith, GL, Randerson-Moor, J, Requena, C, Rowe, C, Samani, NJ, Sanna, M, Schadendorf, D
Most genetic susceptibility to cutaneous melanoma remains to be discovered. Meta-analysis genome-wide association study (GWAS) of 36,760 cases of melanoma (67% newly genotyped) and 375,188 controls identified 54 significant (P < 5 × 10-8) loci with 68 independent single nucleotide polymorphisms. Analysis of risk estimates across geographical regions and host factors suggests the acral melanoma subtype is uniquely unrelated to pigmentation. Combining this meta-analysis with GWAS of nevus count and hair color, and transcriptome association approaches, uncovered 31 potential secondary loci for a total of 85 cutaneous melanoma susceptibility loci. These findings provide insights into cutaneous melanoma genetic architecture, reinforcing the importance of nevogenesis, pigmentation and telomere maintenance, together with identifying potential new pathways for cutaneous melanoma pathogenesis.


Publication title

Nature Genetics










Menzies Institute for Medical Research


Nature Pub. Co.

Place of publication

United States

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  • Restricted

Socio-economic Objectives

Expanding knowledge in the biomedical and clinical sciences

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