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

Authors
Landi, MT
Bishop, 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. A.
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
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Abstract
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 Genetics
URI
http://hdl.handle.net/10541/623052
DOI
10.1038/s41588-020-0611-8
PubMed ID
32341527
Additional Links
https://dx.doi.org/10.1038/s41588-020-0611-8
Type
Article
Language
en
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