TY - JOUR
T1 - Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways
AU - Duffy, David L.
AU - Zhu, Gu
AU - Li, Xin
AU - Sanna, Marianna
AU - Iles, Mark M.
AU - Jacobs, Leonie C.
AU - Evans, David M.
AU - Yazar, Seyhan
AU - Beesley, Jonathan
AU - Law, Matthew H.
AU - Kraft, Peter
AU - Visconti, Alessia
AU - Taylor, John C.
AU - Liu, Fan
AU - Wright, Margaret J.
AU - Henders, Anjali K.
AU - Bowdler, Lisa
AU - Glass, Dan
AU - Ikram, M. Arfan
AU - Uitterlinden, André G.
AU - Madden, Pamela A.
AU - Nelson, Elliot C.
AU - Heath, Andrew C.
AU - Green, Adele C.
AU - Chanock, Stephen
AU - Barrett, Jennifer H.
AU - Brown, Matthew A.
AU - Hayward, Nicholas K.
AU - MacGregor, Stuart
AU - Sturm, Richard A.
AU - Hewitt, Alex W.
AU - Melanoma GWAS Consortium
AU - Lee, Jeffrey E.
AU - Brossard, Myriam
AU - Moses, Eric K.
AU - Song, Fengju
AU - Kumar, Rajiv
AU - Easton, Douglas F.
AU - Pharoah, Paul D.P.
AU - Swerdlow, Anthony J.
AU - Kypreou, Katerina P.
AU - Harland, Mark
AU - Randerson-Moor, Juliette
AU - Akslen, Lars A.
AU - Andresen, Per A.
AU - Avril, Marie Françoise
AU - Azizi, Esther
AU - Scarrà, Giovanna Bianchi
AU - Brown, Kevin M.
AU - Dębniak, Tadeusz
AU - Elder, David E.
AU - Fang, Shenying
AU - Friedman, Eitan
AU - Galan, Pilar
AU - Ghiorzo, Paola
AU - Gillanders, Elizabeth M.
AU - Goldstein, Alisa M.
AU - Gruis, Nelleke A.
AU - Hansson, Johan
AU - Helsing, Per
AU - Hočevar, Marko
AU - Höiom, Veronica
AU - Ingvar, Christian
AU - Kanetsky, Peter A.
AU - Chen, Wei V.
AU - Landi, Maria Teresa
AU - Lang, Julie
AU - Lathrop, G. Mark
AU - Lubiński, Jan
AU - Mackie, Rona M.
AU - Mann, Graham J.
AU - Molven, Anders
AU - Novaković, Srdjan
AU - Olsson, Håkan
AU - Puig, Susana
AU - Puig-Butille, Joan Anton
AU - Radford-Smith, Graham L.
AU - van der Stoep, Nienke
AU - van Doorn, Remco
AU - Whiteman, David C.
AU - Craig, Jamie E.
AU - Schadendorf, Dirk
AU - Simms, Lisa A.
AU - Burdon, Kathryn P.
AU - Nyholt, Dale R.
AU - Pooley, Karen A.
AU - Orr, Nicholas
AU - Stratigos, Alexander J.
AU - Cust, Anne E.
AU - Ward, Sarah V.
AU - Schulze, Hans Joachim
AU - Dunning, Alison M.
AU - Demenais, Florence
AU - Amos, Christopher I.
AU - Kayser, Manfred
AU - Hunter, David J.
AU - Newton Bishop, Julia A.
AU - Spector, Timothy D.
AU - Montgomery, Grant W.
AU - Mackey, David A.
AU - Smith, George Davey
AU - Nijsten, Tamar E.
AU - Bishop, D. Timothy
AU - Bataille, Veronique
AU - Falchi, Mario
AU - Han, Jiali
AU - Martin, Nicholas G.
N1 - CC-BY This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
PY - 2018/12/1
Y1 - 2018/12/1
N2 - The total number of acquired melanocytic nevi on the skin is strongly correlated with melanoma risk. Here we report a meta-analysis of 11 nevus GWAS from Australia, Netherlands, UK, and USA comprising 52,506 individuals. We confirm known loci including MTAP, PLA2G6, and IRF4, and detect novel SNPs in KITLG and a region of 9q32. In a bivariate analysis combining the nevus results with a recent melanoma GWAS meta-analysis (12,874 cases, 23,203 controls), SNPs near GPRC5A, CYP1B1, PPARGC1B, HDAC4, FAM208B, DOCK8, and SYNE2 reached global significance, and other loci, including MIR146A and OBFC1, reached a suggestive level. Overall, we conclude that most nevus genes affect melanoma risk (KITLG an exception), while many melanoma risk loci do not alter nevus count. For example, variants in TERC and OBFC1 affect both traits, but other telomere length maintenance genes seem to affect melanoma risk only. Our findings implicate multiple pathways in nevogenesis.
AB - The total number of acquired melanocytic nevi on the skin is strongly correlated with melanoma risk. Here we report a meta-analysis of 11 nevus GWAS from Australia, Netherlands, UK, and USA comprising 52,506 individuals. We confirm known loci including MTAP, PLA2G6, and IRF4, and detect novel SNPs in KITLG and a region of 9q32. In a bivariate analysis combining the nevus results with a recent melanoma GWAS meta-analysis (12,874 cases, 23,203 controls), SNPs near GPRC5A, CYP1B1, PPARGC1B, HDAC4, FAM208B, DOCK8, and SYNE2 reached global significance, and other loci, including MIR146A and OBFC1, reached a suggestive level. Overall, we conclude that most nevus genes affect melanoma risk (KITLG an exception), while many melanoma risk loci do not alter nevus count. For example, variants in TERC and OBFC1 affect both traits, but other telomere length maintenance genes seem to affect melanoma risk only. Our findings implicate multiple pathways in nevogenesis.
KW - pleiotropic risk
KW - melanocytic nevus
KW - Meta-analysis
KW - melanoma risk
KW - nevogenesis pathways
KW - gene variation
UR - http://www.scopus.com/inward/record.url?scp=85047573234&partnerID=8YFLogxK
U2 - 10.1038/s41467-018-06649-5
DO - 10.1038/s41467-018-06649-5
M3 - Article
C2 - 30643134
AN - SCOPUS:85047573234
VL - 9
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 4774
ER -