Genome-wide association meta-analyses combining multiple risk phenotypes provide insights into the genetic architecture of cutaneous melanoma susceptibility
Landi, MT Bishop, D T MacGregor, S Machiela, MJ Stratigos, AJ Ghiorzo, P Brossard, M Calista, D Choi, J. Fargnoli, MC
Landi, MT
Bishop, D T
MacGregor, S
Machiela, MJ
Stratigos, AJ
Ghiorzo, P
Brossard, M
Calista, D
Choi, J.
Fargnoli, MC
Citations
Altmetric:
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.
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.
Essen-Heidelberg, I.
MelaNostrum, C.
Peris, K.
Chanock, S. J.
Demenais, F.
Brown, K. M.
Puig, S.
Nagore, E.
Shi, J.
Iles, M. M.
Law, M. H.
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.
Essen-Heidelberg, I.
MelaNostrum, C.
Peris, K.
Chanock, S. J.
Demenais, F.
Brown, K. M.
Puig, S.
Nagore, E.
Shi, J.
Iles, M. M.
Law, M. H.
Description
Date
2020
Publisher
Collections
Keywords
Type
Article
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.