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

Maria Teresa Landi 1 D. Timothy Bishop 2 Stuart Macgregor 3 Mitchell Machiela 1 Alexander Stratigos 4 Paola Ghiorzo 5, 6 Myriam Brossard 7 Donato Calista 8 Jiyeon Choi 1 Maria Concetta Fargnoli 9 Tongwu Zhang 1 Monica Rodolfo 10 Adam Trower 2 Chiara Menin Jacobo Martinez 11 Andreas Hadjisavvas 12 Lei Song 1 Irene Stefanaki 13 Richard Scolyer 14 Rose Yang 1 Alisa Goldstein 1 Miriam Potrony 15 Katerina Kypreou 13 Lorenza Pastorino 5 Paola Queirolo 5 Cristina Pellegrini 9 Laura Cattaneo 16 Matthew Zawistowski 17 Pol Gimenez-Xavier 15 Arantxa Rodriguez 18 Lisa Elefanti 19 Siranoush Manoukian 20 Licia Rivoltini 20 Blair Smith 21 Maria Loizidou 22 Laura del Regno 23 Daniela Massi 24 Mario Mandala 16 Kiarash Khosrotehrani 25 Lars Akslen 26 Christopher Amos 27 Per Andresen 28 Marie-Françoise Avril 29 Esther Azizi 30 H. Peter Soyer 25 Veronique Bataille 31 Bruna Dalmasso 5 Lisa Bowdler 3 Kathryn Burdon 32 Wei Chen 33 Veryan Codd 34 Jamie Craig 35 Tadeusz Dębniak 36 Mario Falchi 31 Shenying Fang 33 Eitan Friedman 30 Sarah Simi 24 Pilar Galan 37 Zaida Garcia-Casado 18 Elizabeth Gillanders 38 Scott Gordon 3 Adele Green 3 Nelleke Gruis 39 Johan Hansson 40 Mark Harland 2 Jessica Harris 41 Per Helsing 28 Anjali Henders 25 Marko Hočevar 42 Veronica Höiom 40 David Hunter 43 Christian Ingvar 44 Rajiv Kumar 45 Julie Lang 46 G. Mark Lathrop Jeffrey Lee Xin Li Jan Lubiński Rona Mackie Maryrose Malt Josep Malvehy Kerrie Mcaloney Hamida Mohamdi Anders Molven Eric Moses Rachel Neale Srdjan Novaković Dale Nyholt Håkan Olsson Nicholas Orr Lars Fritsche Joan Anton Puig-Butille Abrar Qureshi Graham Radford-Smith Juliette Randerson-Moor Celia Requena Casey Rowe Nilesh Samani Marianna Sanna Dirk Schadendorf Hans-Joachim Schulze Lisa Simms Mark Smithers Fengju Song Anthony Swerdlow Nienke van der Stoep Nicole Kukutsch Alessia Visconti Leanne Wallace Sarah Ward Lawrie Wheeler Richard Sturm Amy Hutchinson Kristine Jones Michael Malasky Aurelie Vogt Weiyin Zhou Karen Pooley David Elder Jiali Han Belynda Hicks Nicholas Hayward Peter Kanetsky Chad Brummett Grant Montgomery Catherine Olsen Caroline Hayward Alison Dunning Nicholas Martin Evangelos Evangelou Graham Mann Georgina Long Paul Pharoah Douglas Easton Jennifer Barrett Anne Cust Goncalo Abecasis David Duffy David Whiteman Helen Gogas Arcangela de Nicolo Margaret Tucker Julia Newton-Bishop Ketty Peris Stephen Chanock Florence Demenais Kevin Brown Susana Puig Eduardo Nagore Jianxin Shi Mark Iles Matthew Law 47, *
* Corresponding author
37 CRESS - U1153 - Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle
Université Sorbonne Paris Nord, CRESS (U1153 / UMR_A_1125 / UMR_S_1153) - Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité
Abstract : Meta-analysis of 36,760 cases and 375,188 controls identifies 54 loci associated with susceptibility to cutaneous melanoma. Further analysis combining nevus count and hair color GWAS results provide insights into the genetic architecture of melanoma. 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.
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Submitted on : Monday, November 9, 2020 - 10:23:21 AM
Last modification on : Thursday, June 3, 2021 - 3:23:56 AM

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Maria Teresa Landi, D. Timothy Bishop, Stuart Macgregor, Mitchell Machiela, Alexander Stratigos, et al.. Genome-wide association meta-analyses combining multiple risk phenotypes provide insights into the genetic architecture of cutaneous melanoma susceptibility. Nature Genetics, Nature Publishing Group, 2020, 52 (5), pp.494-504. ⟨10.1038/s41588-020-0611-8⟩. ⟨hal-02995377⟩

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