학술논문
Genome-wide association meta-analyses combining multiple risk phenotypes provide insights into the genetic architecture of cutaneous melanoma susceptibility
Document Type
Article
Author
Landi, Maria Teresa; Bishop, D. Timothy; MacGregor, Stuart; Machiela, Mitchell J.; Stratigos, Alexander J.; Ghiorzo, Paola; Brossard, Myriam; Calista, Donato; Choi, Jiyeon; Fargnoli, Maria Concetta; Zhang, Tongwu; Rodolfo, Monica; Trower, Adam J.; Menin, Chiara; Martinez, Jacobo; Hadjisavvas, Andreas; Song, Lei; Stefanaki, Irene; Scolyer, Richard; Yang, Rose; Goldstein, Alisa M.; Potrony, Miriam; Kypreou, Katerina P.; Pastorino, Lorenza; Queirolo, Paola; Pellegrini, Cristina; Cattaneo, Laura; Zawistowski, Matthew; Gimenez-Xavier, Pol; Rodriguez, Arantxa; Elefanti, Lisa; Manoukian, Siranoush; Rivoltini, Licia; Smith, Blair H.; Loizidou, Maria A.; Del Regno, Laura; Massi, Daniela; Mandala, Mario; Khosrotehrani, Kiarash; Akslen, Lars A.; Amos, Christopher I.; Andresen, Per A.; Avril, Marie-Françoise; Azizi, Esther; Soyer, H. Peter; Bataille, Veronique; Dalmasso, Bruna; Bowdler, Lisa M.; Burdon, Kathryn P.; Chen, Wei V.; Codd, Veryan; Craig, Jamie E.; Dębniak, Tadeusz; Falchi, Mario; Fang, Shenying; Friedman, Eitan; Simi, Sarah; Galan, Pilar; Garcia-Casado, Zaida; Gillanders, Elizabeth M.; Gordon, Scott; Green, Adele; Gruis, Nelleke A.; Hansson, Johan; Harland, Mark; Harris, Jessica; Helsing, Per; Henders, Anjali; Hočevar, Marko; Höiom, Veronica; Hunter, David; Ingvar, Christian; Kumar, Rajiv; Lang, Julie; Lathrop, G. Mark; Lee, Jeffrey E.; Li, Xin; Lubiński, Jan; Mackie, Rona M.; Malt, Maryrose; Malvehy, Josep; McAloney, Kerrie; Mohamdi, Hamida; Molven, Anders; Moses, Eric K.; Neale, Rachel E.; Novaković, Srdjan; Nyholt, Dale R.; Olsson, Håkan; Orr, Nicholas; Fritsche, Lars G.; Puig-Butille, Joan Anton; Qureshi, Abrar A.; Radford-Smith, Graham L.; Randerson-Moor, Juliette; Requena, Celia; Rowe, Casey; Samani, Nilesh J.; Sanna, Marianna; Schadendorf, Dirk; Schulze, Hans-Joachim; Simms, Lisa A.; Smithers, Mark; Song, Fengju; Swerdlow, Anthony J.; van der Stoep, Nienke; Kukutsch, Nicole A.; Visconti, Alessia; Wallace, Leanne; Ward, Sarah V.; Wheeler, Lawrie; Sturm, Richard A.; Hutchinson, Amy; Jones, Kristine; Malasky, Michael; Vogt, Aurelie; Zhou, Weiyin; Pooley, Karen A.; Elder, David E.; Han, Jiali; Hicks, Belynda; Hayward, Nicholas K.; Kanetsky, Peter A.; Brummett, Chad; Montgomery, Grant W.; Olsen, Catherine M.; Hayward, Caroline; Dunning, Alison M.; Martin, Nicholas G.; Evangelou, Evangelos; Mann, Graham J.; Long, Georgina; Pharoah, Paul D. P.; Easton, Douglas F.; Barrett, Jennifer H.; Cust, Anne E.; Abecasis, Goncalo; Duffy, David L.; Whiteman, David C.; Gogas, Helen; De Nicolo, Arcangela; Tucker, Margaret A.; Newton-Bishop, Julia A.; Peris, Ketty; Chanock, Stephen J.; Demenais, Florence; Brown, Kevin M.; Puig, Susana; Nagore, Eduardo; Shi, Jianxin; Iles, Mark M.; Law, Matthew H.
Source
Nature Genetics; May 2020, Vol. 52 Issue: 5 p494-504, 11p
Subject
Language
ISSN
10614036; 15461718
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.