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

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    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
    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.
    Show allShow less
    Affiliation
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD,
    Issue Date
    2020
    
    Metadata
    Show full item record
    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
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41588-020-0611-8
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

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