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

Landi, Maria Teresa ; Bishop, D Timothy ; MacGregor, Stuart ; Machiela, Mitchell J ; Stratigos, Alexander J ; Ghiorzo, Paola ; Brossard, Myriam ; Calista, Donato ; Choi, Jiyeon and Fargnoli, Maria Concetta , et al. (2020) In Nature Genetics 52(5). p.494-504
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... (More)

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.

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Contribution to journal
publication status
published
subject
in
Nature Genetics
volume
52
issue
5
pages
11 pages
publisher
Nature Publishing Group
external identifiers
  • pmid:32341527
  • scopus:85084007486
ISSN
1546-1718
DOI
10.1038/s41588-020-0611-8
language
English
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yes
id
9a2b5113-a5de-4550-b235-73b458bab253
date added to LUP
2020-05-01 17:58:55
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2021-02-17 07:19:31
@article{9a2b5113-a5de-4550-b235-73b458bab253,
  abstract     = {<p>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 &lt; 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.</p>},
  author       = {Landi, Maria Teresa and Bishop, D Timothy and MacGregor, Stuart and Machiela, Mitchell J and Stratigos, Alexander J and Ghiorzo, Paola and Brossard, Myriam and Calista, Donato and Choi, Jiyeon and Fargnoli, Maria Concetta and Zhang, Tongwu and Rodolfo, Monica and Trower, Adam J and Menin, Chiara and Martinez, Jacobo and Hadjisavvas, Andreas and Song, Lei and Stefanaki, Irene and Scolyer, Richard and Yang, Rose and Goldstein, Alisa M and Potrony, Miriam and Kypreou, Katerina P and Pastorino, Lorenza and Queirolo, Paola and Pellegrini, Cristina and Cattaneo, Laura and Zawistowski, Matthew and Gimenez-Xavier, Pol and Rodriguez, Arantxa and Elefanti, Lisa and Manoukian, Siranoush and Rivoltini, Licia and Smith, Blair H and Loizidou, Maria A and Del Regno, Laura and Massi, Daniela and Mandala, Mario and Khosrotehrani, Kiarash and Akslen, Lars A and Amos, Christopher I and Andresen, Per A and Avril, Marie-Françoise and Azizi, Esther and Soyer, H Peter and Bataille, Veronique and Dalmasso, Bruna and Bowdler, Lisa M and Burdon, Kathryn P and Ingvar, Christian},
  issn         = {1546-1718},
  language     = {eng},
  number       = {5},
  pages        = {494--504},
  publisher    = {Nature Publishing Group},
  series       = {Nature Genetics},
  title        = {Genome-wide association meta-analyses combining multiple risk phenotypes provide insights into the genetic architecture of cutaneous melanoma susceptibility},
  url          = {http://dx.doi.org/10.1038/s41588-020-0611-8},
  doi          = {10.1038/s41588-020-0611-8},
  volume       = {52},
  year         = {2020},
}