TY - JOUR
T1 - Genome-wide association meta-analyses combining multiple risk phenotypes provide insights into the genetic architecture of cutaneous melanoma susceptibility
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 - Mann, Graham J.
N1 - Publisher Copyright:
© 2020, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.
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 - http://www.scopus.com/inward/record.url?scp=85084007486&partnerID=8YFLogxK
U2 - 10.1038/s41588-020-0611-8
DO - 10.1038/s41588-020-0611-8
M3 - Article
SN - 1061-4036
VL - 52
SP - 494
EP - 504
JO - Nature Genetics
JF - Nature Genetics
IS - 5
ER -