| Authors: |
Landi, M. T.; Bishop, D. T.; MacGregor, S.; Machiela, M. J.; Stratigos, A. J.; Ghiorzo, P.; Brossard, M.; Calista, D.; Choi, J.; Fargnoli, M. C.; Zhang, T.; Rodolfo, M.; Trower, A. J.; Menin, C.; Martinez, J.; Hadjisavvas, A.; Song, L.; Stefanaki, I.; Scolyer, R.; Yang, R.; Goldstein, A. M.; Potrony, M.; Kypreou, K. P.; 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.; Dębniak, T.; Falchi, M.; Fang, S.; Friedman, E.; Simi, S.; Galan, P.; Garcia-Casado, Z.; Gillanders, E. M.; Gordon, S.; Green, A.; Gruis, N. A.; Hansson, J.; Harland, M.; Harris, J.; Helsing, P.; Henders, A.; Hočevar, M.; Höiom, V.; Hunter, D.; Ingvar, C.; Kumar, R.; Lang, J.; Lathrop, G. M.; Lee, J. E.; Li, X.; Lubiński, J.; Mackie, R. M.; Malt, M.; Malvehy, J.; McAloney, K.; Mohamdi, H.; Molven, A.; Moses, E. K.; Neale, R. E.; Novaković, 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.; GenoMEL Consortium; Q-MEGA and QTWIN Investigators; ATHENS Melanoma Study Group; 23andMe; SDH Study Group; IBD Investigators; Essen-Heidelberg Investigators; AMFS Investigators; MelaNostrum Consortium; Peris, K.; Chanock, S. J.; Demenais, F.; Brown, K. M.; Puig, S.; Nagore, E.; Shi, J.; Iles, M. M.; Law, M. H. |
| Article Title: |
Genome-wide association meta-analyses combining multiple risk phenotypes provide insights into the genetic architecture of cutaneous melanoma susceptibility |
| 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 × 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. © 2020, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply. |
| Keywords: |
controlled study; unclassified drug; major clinical study; single nucleotide polymorphism; case control study; cancer risk; phenotype; cancer susceptibility; melanoma; skin pigmentation; nevus; malignant lentigo; cohort analysis; gene locus; genetic association; genotype; genome-wide association study; transcriptomics; protein p53; uvomorulin; tumor marker; risk assessment; hair color; cancer genetics; genetic susceptibility; hla antigen class 2; genetic risk; microphthalmia associated transcription factor; transcriptome; cutaneous melanoma; interferon regulatory factor 4; gene structure; adam15 protein; superficial spreading melanoma; kruppel like factor 4; notch2 receptor; histone deacetylase 4; peptides and proteins; peroxisome proliferator activated receptor gamma coactivator 1beta; host factor; telomere homeostasis; human; male; female; priority journal; article; acral lentiginous melanoma; medical geography; alpha ketoglutarate dependent dioxygenase fto; dstyk protein; dtnb protein; foxd3 protein; gba protein; hdgfl1 protein; hla dqb2 antigen; kiaa0930 protein; mfsd12 protein; plxnb2 protein; pot1 protein; rapgef5 protein; retl1 protein; terc protein; transcription factor sox6; zbtb7b protein
|
| Journal Title: |
Nature Genetics
|
| Volume: |
52 |
| Issue: |
5 |
| ISSN: |
1061-4036 |
| Publisher: |
Nature Publishing Group
|
| Date Published: |
2020-05-01 |
| Start Page: |
494 |
| End Page: |
504 |
| Language: |
English |
| DOI: |
10.1038/s41588-020-0611-8
|
| PUBMED: |
32341527
|
| PROVIDER: |
scopus
|
| PMCID: |
PMC7255059
|
| DOI/URL: |
|
| Notes: |
Article -- Export Date: 1 June 2020 -- Source: Scopus |
