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

AMFS Investigators; MelaNostrum Consortium; GenoMEL Consortium; Q-MEGA and QTWIN Investigators; ATHENS Melanoma Study Group; 23andMe; The SDH Study Group; IBD Investigators; Essen-Heidelberg Investigators; Maria Teresa Landi; D. Timothy Bishop; Stuart MacGregor; Mitchell J. Machiela; Alexander J. Stratigos; Paola Ghiorzo; Myriam Brossard; Donato Calista; Jiyeon Choi; Maria Concetta Fargnoli; Tongwu Zhang; Monica Rodolfo; Adam J. Trower; Chiara Menin; Jacobo Martinez; Andreas Hadjisavvas; Lei Song; Irene Stefanaki; Richard Scolyer; Rose Yang; Alisa M. Goldstein; Miriam Potrony; Katerina P. Kypreou; Lorenza Pastorino; Paola Queirolo; Cristina Pellegrini; Laura Cattaneo; Matthew Zawistowski; Pol Gimenez-Xavier; Arantxa Rodriguez; Lisa Elefanti; Siranoush Manoukian; Licia Rivoltini; Blair H. Smith; Maria A. Loizidou; Laura Del Regno; Daniela Massi; Mario Mandala; Kiarash Khosrotehrani; Lars A. Akslen; Christopher I. Amos; Per A. Andresen; Marie Françoise Avril; Esther Azizi; H. Peter Soyer; Veronique Bataille; Bruna Dalmasso; Lisa M. Bowdler; Kathryn P. Burdon; Wei V. Chen; Veryan Codd; Jamie E. Craig; Tadeusz Dębniak; Mario Falchi; Shenying Fang; Eitan Friedman; Sarah Simi; Pilar Galan; Zaida Garcia-Casado; Elizabeth M. Gillanders; Scott Gordon; Adele Green; Nelleke A. Gruis; Johan Hansson; Mark Harland; Jessica Harris; Per Helsing; Anjali Henders; Marko Hočevar; Veronica Höiom; David Hunter; Christian Ingvar; Rajiv Kumar; Julie Lang; G. Mark Lathrop; Jeffrey E. Lee; Xin Li; Jan Lubiński; Rona M. Mackie; Maryrose Malt; Josep Malvehy; Kerrie McAloney; Hamida Mohamdi; Anders Molven; Eric K. Moses; Rachel E. Neale; Srdjan Novaković; Dale R. Nyholt; Håkan Olsson; Nicholas Orr; Lars G. Fritsche; Joan Anton Puig-Butille; Abrar A. Qureshi; Graham L. Radford-Smith; Juliette Randerson-Moor; Celia Requena; Casey Rowe; Nilesh J. Samani; Marianna Sanna; Dirk Schadendorf; Hans Joachim Schulze; Lisa A. Simms; Mark Smithers; Fengju Song; Anthony J. Swerdlow; Nienke van der Stoep; Nicole A. Kukutsch; Alessia Visconti; Leanne Wallace; Sarah V. Ward; Lawrie Wheeler; Richard A. Sturm; Amy Hutchinson; Kristine Jones; Michael Malasky; Aurelie Vogt; Weiyin Zhou; Karen A. Pooley; David E. Elder; Jiali Han; Belynda Hicks; Nicholas K. Hayward; Peter A. Kanetsky; Chad Brummett; Grant W. Montgomery; Catherine M. Olsen; Caroline Hayward; Alison M. Dunning; Nicholas G. Martin; Evangelos Evangelou; Graham J. Mann; Georgina Long; Paul D.P. Pharoah; Douglas F. Easton; Jennifer H. Barrett; Anne E. Cust; Goncalo Abecasis; David L. Duffy; David C. Whiteman; Helen Gogas; Arcangela De Nicolo; Margaret A. Tucker; Julia A. Newton-Bishop; Ketty Peris; Stephen J. Chanock; Florence Demenais; Kevin M. Brown; Susana Puig; Eduardo Nagore; Jianxin Shi; Mark M. Iles; Matthew H. Law

doi:10.1038/s41588-020-0611-8

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

AMFS Investigators
, MelaNostrum Consortium
, GenoMEL Consortium
, Q-MEGA and QTWIN Investigators
, ATHENS Melanoma Study Group
, 23andMe
, The SDH Study Group
, IBD Investigators
, Essen-Heidelberg Investigators
, Maria Teresa Landi (Corresponding Author)
, D. Timothy Bishop
, Stuart MacGregor
, Mitchell J. Machiela
, Alexander J. Stratigos
, Paola Ghiorzo
, Myriam Brossard
, Donato Calista
, Jiyeon Choi
, Maria Concetta Fargnoli
, Tongwu Zhang

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

Research output: Contribution to journal › Article › peer-review

175 Citations (Scopus)

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.

Original language	English
Pages (from-to)	494-504
Number of pages	11
Journal	Nature Genetics
Volume	52
Issue number	5
DOIs	https://doi.org/10.1038/s41588-020-0611-8
Publication status	Published - 1 May 2020
Externally published	Yes

Field of Science*

3.2 Clinical medicine

Publication Type*

1.1. Scientific article indexed in Web of Science and/or Scopus database

Access to Document

10.1038/s41588-020-0611-8

Cite this

AMFS Investigators, MelaNostrum Consortium, GenoMEL Consortium, Q-MEGA and QTWIN Investigators, ATHENS Melanoma Study Group, 23andMe, The SDH Study Group, IBD Investigators, Essen-Heidelberg Investigators, 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., ... Law, M. H. (2020). Genome-wide association meta-analyses combining multiple risk phenotypes provide insights into the genetic architecture of cutaneous melanoma susceptibility. Nature Genetics, 52(5), 494-504. https://doi.org/10.1038/s41588-020-0611-8

@article{11538ceae1a9408e9f34d47dd8b35f92,

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.",

author = "\{AMFS Investigators\} and \{MelaNostrum Consortium\} and \{GenoMEL Consortium\} and \{Q-MEGA and QTWIN Investigators\} and \{ATHENS Melanoma Study Group\} and 23andMe and \{The SDH Study Group\} and \{IBD Investigators\} and \{Essen-Heidelberg Investigators\} and Landi, \{Maria Teresa\} and Bishop, \{D. Timothy\} and Stuart MacGregor and Machiela, \{Mitchell J.\} and Stratigos, \{Alexander J.\} and Paola Ghiorzo and Myriam Brossard and Donato Calista and Jiyeon Choi and Fargnoli, \{Maria Concetta\} and Tongwu Zhang and Monica Rodolfo and Trower, \{Adam J.\} and Chiara Menin and Jacobo Martinez and Andreas Hadjisavvas and Lei Song and Irene Stefanaki and Richard Scolyer and Rose Yang and Goldstein, \{Alisa M.\} and Miriam Potrony and Kypreou, \{Katerina P.\} and Lorenza Pastorino and Paola Queirolo and Cristina Pellegrini and Laura Cattaneo and Matthew Zawistowski and Pol Gimenez-Xavier and Arantxa Rodriguez and Lisa Elefanti and Siranoush Manoukian and Licia Rivoltini and Smith, \{Blair H.\} and Loizidou, \{Maria A.\} and \{Del Regno\}, Laura and Daniela Massi and Mario Mandala and Kiarash Khosrotehrani and Akslen, \{Lars A.\} and Amos, \{Christopher I.\} and Andresen, \{Per A.\} and Avril, \{Marie Fran{\c c}oise\} and Esther Azizi and Soyer, \{H. Peter\} and Veronique Bataille and Bruna Dalmasso and Bowdler, \{Lisa M.\} and Burdon, \{Kathryn P.\} and Chen, \{Wei V.\} and Veryan Codd and Craig, \{Jamie E.\} and Tadeusz D{\c e}bniak and Mario Falchi and Shenying Fang and Eitan Friedman and Sarah Simi and Pilar Galan and Zaida Garcia-Casado and Gillanders, \{Elizabeth M.\} and Scott Gordon and Adele Green and Gruis, \{Nelleke A.\} and Johan Hansson and Mark Harland and Jessica Harris and Per Helsing and Anjali Henders and Marko Ho{\v c}evar and Veronica H{\"o}iom and David Hunter and Christian Ingvar and Rajiv Kumar and Julie Lang and Lathrop, \{G. Mark\} and Lee, \{Jeffrey E.\} and Xin Li and Jan Lubi{\'n}ski and Mackie, \{Rona M.\} and Maryrose Malt and Josep Malvehy and Kerrie McAloney and Hamida Mohamdi and Anders Molven and Moses, \{Eric K.\} and Neale, \{Rachel E.\} and Srdjan Novakovi{\'c} and Nyholt, \{Dale R.\} and H{\aa}kan Olsson and Nicholas Orr and Fritsche, \{Lars G.\} and Puig-Butille, \{Joan Anton\} and Qureshi, \{Abrar A.\} and Radford-Smith, \{Graham L.\} and Juliette Randerson-Moor and Celia Requena and Casey Rowe and Samani, \{Nilesh J.\} and Marianna Sanna and Dirk Schadendorf and Schulze, \{Hans Joachim\} and Simms, \{Lisa A.\} and Mark Smithers and Fengju Song and Swerdlow, \{Anthony J.\} and \{van der Stoep\}, Nienke and Kukutsch, \{Nicole A.\} and Alessia Visconti and Leanne Wallace and Ward, \{Sarah V.\} and Lawrie Wheeler and Sturm, \{Richard A.\} and Amy Hutchinson and Kristine Jones and Michael Malasky and Aurelie Vogt and Weiyin Zhou and Pooley, \{Karen A.\} and Elder, \{David E.\} and Jiali Han and Belynda Hicks and Hayward, \{Nicholas K.\} and Kanetsky, \{Peter A.\} and Chad Brummett and Montgomery, \{Grant W.\} and Olsen, \{Catherine M.\} and Caroline Hayward and Dunning, \{Alison M.\} and Martin, \{Nicholas G.\} and Evangelos Evangelou and Mann, \{Graham J.\} and Georgina Long and Pharoah, \{Paul D.P.\} and Easton, \{Douglas F.\} and Barrett, \{Jennifer H.\} and Cust, \{Anne E.\} and Goncalo Abecasis and Duffy, \{David L.\} and Whiteman, \{David C.\} and Helen Gogas and \{De Nicolo\}, Arcangela and Tucker, \{Margaret A.\} and Newton-Bishop, \{Julia A.\} and Ketty Peris and Chanock, \{Stephen J.\} and Florence Demenais and Brown, \{Kevin M.\} and Susana Puig and Eduardo Nagore and Jianxin Shi and Iles, \{Mark M.\} and Law, \{Matthew H.\}",

note = "Publisher Copyright: {\textcopyright} 2020, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.",

year = "2020",

month = may,

day = "1",

doi = "10.1038/s41588-020-0611-8",

language = "English",

volume = "52",

pages = "494--504",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "5",

}

AMFS Investigators, MelaNostrum Consortium, GenoMEL Consortium, Q-MEGA and QTWIN Investigators, ATHENS Melanoma Study Group, 23andMe, The SDH Study Group, IBD Investigators, Essen-Heidelberg Investigators, Landi, MT, Bishop, DT, 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, BH, Loizidou, MA, Del Regno, L, Massi, D, Mandala, M, Khosrotehrani, K, Akslen, LA, Amos, CI, Andresen, PA, Avril, MF, Azizi, E, Soyer, HP, Bataille, V, Dalmasso, B, Bowdler, LM, Burdon, KP, Chen, WV, Codd, V, Craig, JE, Dębniak, T, Falchi, M, Fang, S, Friedman, E, Simi, S, Galan, P, Garcia-Casado, Z, Gillanders, EM, Gordon, S, Green, A, Gruis, NA, Hansson, J, Harland, M, Harris, J, Helsing, P, Henders, A, Hočevar, M, Höiom, V, Hunter, D, Ingvar, C, Kumar, R, Lang, J, Lathrop, GM, Lee, JE, Li, X, Lubiński, J, Mackie, RM, Malt, M, Malvehy, J, McAloney, K, Mohamdi, H, Molven, A, Moses, EK, Neale, RE, Novaković, S, Nyholt, DR, Olsson, H, Orr, N, Fritsche, LG, Puig-Butille, JA, Qureshi, AA, Radford-Smith, GL, Randerson-Moor, J, Requena, C, Rowe, C, Samani, NJ, Sanna, M, Schadendorf, D, Schulze, HJ, Simms, LA, Smithers, M, Song, F, Swerdlow, AJ, van der Stoep, N, Kukutsch, NA, Visconti, A, Wallace, L, Ward, SV, Wheeler, L, Sturm, RA, Hutchinson, A, Jones, K, Malasky, M, Vogt, A, Zhou, W, Pooley, KA, Elder, DE, Han, J, Hicks, B, Hayward, NK, Kanetsky, PA, Brummett, C, Montgomery, GW, Olsen, CM, Hayward, C, Dunning, AM, Martin, NG, Evangelou, E, Mann, GJ, Long, G, Pharoah, PDP, Easton, DF, Barrett, JH, Cust, AE, Abecasis, G, Duffy, DL, Whiteman, DC, Gogas, H, De Nicolo, A, Tucker, MA, Newton-Bishop, JA, Peris, K, Chanock, SJ, Demenais, F, Brown, KM, Puig, S, Nagore, E, Shi, J, Iles, MM & Law, MH 2020, 'Genome-wide association meta-analyses combining multiple risk phenotypes provide insights into the genetic architecture of cutaneous melanoma susceptibility', Nature Genetics, vol. 52, no. 5, pp. 494-504. https://doi.org/10.1038/s41588-020-0611-8

TY - JOUR

T1 - Genome-wide association meta-analyses combining multiple risk phenotypes provide insights into the genetic architecture of cutaneous melanoma susceptibility

AU - AMFS Investigators

AU - MelaNostrum Consortium

AU - GenoMEL Consortium

AU - Q-MEGA and QTWIN Investigators

AU - ATHENS Melanoma Study Group

AU - 23andMe

AU - The SDH Study Group

AU - IBD Investigators

AU - Essen-Heidelberg Investigators

AU - Landi, Maria Teresa

AU - Bishop, D. Timothy

AU - MacGregor, Stuart

AU - Machiela, Mitchell J.

AU - Stratigos, Alexander J.

AU - Ghiorzo, Paola

AU - Brossard, Myriam

AU - Calista, Donato

AU - Choi, Jiyeon

AU - Fargnoli, Maria Concetta

AU - Zhang, Tongwu

AU - Rodolfo, Monica

AU - Trower, Adam J.

AU - Menin, Chiara

AU - Martinez, Jacobo

AU - Hadjisavvas, Andreas

AU - Song, Lei

AU - Stefanaki, Irene

AU - Scolyer, Richard

AU - Yang, Rose

AU - Goldstein, Alisa M.

AU - Potrony, Miriam

AU - Kypreou, Katerina P.

AU - Pastorino, Lorenza

AU - Queirolo, Paola

AU - Pellegrini, Cristina

AU - Cattaneo, Laura

AU - Zawistowski, Matthew

AU - Gimenez-Xavier, Pol

AU - Rodriguez, Arantxa

AU - Elefanti, Lisa

AU - Manoukian, Siranoush

AU - Rivoltini, Licia

AU - Smith, Blair H.

AU - Loizidou, Maria A.

AU - Del Regno, Laura

AU - Massi, Daniela

AU - Mandala, Mario

AU - Khosrotehrani, Kiarash

AU - Akslen, Lars A.

AU - Amos, Christopher I.

AU - Andresen, Per A.

AU - Avril, Marie Françoise

AU - Azizi, Esther

AU - Soyer, H. Peter

AU - Bataille, Veronique

AU - Dalmasso, Bruna

AU - Bowdler, Lisa M.

AU - Burdon, Kathryn P.

AU - Chen, Wei V.

AU - Codd, Veryan

AU - Craig, Jamie E.

AU - Dębniak, Tadeusz

AU - Falchi, Mario

AU - Fang, Shenying

AU - Friedman, Eitan

AU - Simi, Sarah

AU - Galan, Pilar

AU - Garcia-Casado, Zaida

AU - Gillanders, Elizabeth M.

AU - Gordon, Scott

AU - Green, Adele

AU - Gruis, Nelleke A.

AU - Hansson, Johan

AU - Harland, Mark

AU - Harris, Jessica

AU - Helsing, Per

AU - Henders, Anjali

AU - Hočevar, Marko

AU - Höiom, Veronica

AU - Hunter, David

AU - Ingvar, Christian

AU - Kumar, Rajiv

AU - Lang, Julie

AU - Lathrop, G. Mark

AU - Lee, Jeffrey E.

AU - Li, Xin

AU - Lubiński, Jan

AU - Mackie, Rona M.

AU - Malt, Maryrose

AU - Malvehy, Josep

AU - McAloney, Kerrie

AU - Mohamdi, Hamida

AU - Molven, Anders

AU - Moses, Eric K.

AU - Neale, Rachel E.

AU - Novaković, Srdjan

AU - Nyholt, Dale R.

AU - Olsson, Håkan

AU - Orr, Nicholas

AU - Fritsche, Lars G.

AU - Puig-Butille, Joan Anton

AU - Qureshi, Abrar A.

AU - Radford-Smith, Graham L.

AU - Randerson-Moor, Juliette

AU - Requena, Celia

AU - Rowe, Casey

AU - Samani, Nilesh J.

AU - Sanna, Marianna

AU - Schadendorf, Dirk

AU - Schulze, Hans Joachim

AU - Simms, Lisa A.

AU - Smithers, Mark

AU - Song, Fengju

AU - Swerdlow, Anthony J.

AU - van der Stoep, Nienke

AU - Kukutsch, Nicole A.

AU - Visconti, Alessia

AU - Wallace, Leanne

AU - Ward, Sarah V.

AU - Wheeler, Lawrie

AU - Sturm, Richard A.

AU - Hutchinson, Amy

AU - Jones, Kristine

AU - Malasky, Michael

AU - Vogt, Aurelie

AU - Zhou, Weiyin

AU - Pooley, Karen A.

AU - Elder, David E.

AU - Han, Jiali

AU - Hicks, Belynda

AU - Hayward, Nicholas K.

AU - Kanetsky, Peter A.

AU - Brummett, Chad

AU - Montgomery, Grant W.

AU - Olsen, Catherine M.

AU - Hayward, Caroline

AU - Dunning, Alison M.

AU - Martin, Nicholas G.

AU - Evangelou, Evangelos

AU - Mann, Graham J.

AU - Long, Georgina

AU - Pharoah, Paul D.P.

AU - Easton, Douglas F.

AU - Barrett, Jennifer H.

AU - Cust, Anne E.

AU - Abecasis, Goncalo

AU - Duffy, David L.

AU - Whiteman, David C.

AU - Gogas, Helen

AU - De Nicolo, Arcangela

AU - Tucker, Margaret A.

AU - Newton-Bishop, Julia A.

AU - Peris, Ketty

AU - Chanock, Stephen J.

AU - Demenais, Florence

AU - Brown, Kevin M.

AU - Puig, Susana

AU - Nagore, Eduardo

AU - Shi, Jianxin

AU - Iles, Mark M.

AU - Law, Matthew H.

PY - 2020/5/1

Y1 - 2020/5/1

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85084007486

U2 - 10.1038/s41588-020-0611-8

DO - 10.1038/s41588-020-0611-8

M3 - Article

C2 - 32341527

AN - SCOPUS:85084007486

SN - 1061-4036

VL - 52

SP - 494

EP - 504

JO - Nature Genetics

JF - Nature Genetics

IS - 5

ER -

AMFS Investigators, MelaNostrum Consortium, GenoMEL Consortium, Q-MEGA and QTWIN Investigators, ATHENS Melanoma Study Group, 23andMe et al. Genome-wide association meta-analyses combining multiple risk phenotypes provide insights into the genetic architecture of cutaneous melanoma susceptibility. Nature Genetics. 2020 May 1;52(5):494-504. doi: 10.1038/s41588-020-0611-8

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

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