Genome-wide association meta-analyses combining multiple risk phenotypes provide insights into the genetic architecture of cutaneous melanoma susceptibility
Authors
Landi, MTBishop, D T
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, B. H.
Loizidou, M. A.
Del Regno, L
Massi, D
Mandala, M
Khosrotehrani, K
Akslen, L. A.
Amos, C. I.
Andresen, P. A.
Avril, M. F.
Azizi, E.
Soyer, H. P.
Bataille, V.
Dalmasso, B.
Bowdler, L. M.
Burdon, K. P.
Chen, W. V.
Codd, V.
Craig, J. E.
Debniak, T.
Falchi, M.
Fang, S.
Friedman, E.
Simi, S.
Galan, P.
Garcia-Casado, Z.
Gillanders, E. M.
Gordon, S.
Green, Adèle C
Gruis, N. A.
Hansson, J.
Harland, M.
Harris, J.
Helsing, P.
Henders, A.
Hocevar, M.
Hoiom, V.
Hunter, D.
Ingvar, C.
Kumar, R.
Lang, J.
Lathrop, G. M.
Lee, J. E.
Li, X.
Lubinski, J.
Mackie, R. M.
Malt, M.
Malvehy, J.
McAloney, K.
Mohamdi, H.
Molven, A.
Moses, E. K.
Neale, R. E.
Novakovic, S.
Nyholt, D. R.
Olsson, H.
Orr, N.
Fritsche, L. G.
Puig-Butille, J. A.
Qureshi, A. A.
Radford-Smith, G. L.
Randerson-Moor, J.
Requena, C.
Rowe, C.
Samani, N. J.
Sanna, M.
Schadendorf, D.
Schulze, H. J.
Simms, L. A.
Smithers, M.
Song, F.
Swerdlow, A. J.
van der Stoep, N.
Kukutsch, N. A.
Visconti, A.
Wallace, L.
Ward, S. V.
Wheeler, L.
Sturm, R. A.
Hutchinson, A.
Jones, K.
Malasky, M.
Vogt, A.
Zhou, W.
Pooley, K. A.
Elder, D. E.
Han, J.
Hicks, B.
Hayward, N. K.
Kanetsky, P. A.
Brummett, C.
Montgomery, G. W.
Olsen, C. M.
Hayward, C.
Dunning, A M
Martin, N. G.
Evangelou, E.
Mann, G. J.
Long, G.
Pharoah, P. D. P.
Easton, D. F.
Barrett, J. H.
Cust, A. E.
Abecasis, G.
Duffy, D. L.
Whiteman, D. C.
Gogas, H.
De Nicolo, A.
Tucker, M. A.
Newton-Bishop, J
Geno, M. E. L. C.
Q, M.
Investigators, Q.
Group, A. M. S.
andMe
Group, S. D. H. S.
Investigators, I. B. D.
Essen-Heidelberg, I.
Investigators, A.
MelaNostrum, C.
Peris, K.
Chanock, S. J.
Demenais, F.
Brown, K. M.
Puig, S.
Nagore, E.
Shi, J.
Iles, M. M.
Law, M. H.
Affiliation
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD,Issue Date
2020
Metadata
Show full item recordAbstract
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 x 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.Citation
M. T. Landi, D. T. Bishop, S. MacGregor et al. Genome-wide association meta-analyses combining multiple risk phenotypes provide insights into the genetic architecture of cutaneous melanoma susceptibility. Nat Genet. 2020;52(5):494-504.Journal
Nature GeneticsDOI
10.1038/s41588-020-0611-8PubMed ID
32341527Additional Links
https://dx.doi.org/10.1038/s41588-020-0611-8Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1038/s41588-020-0611-8
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