TY - JOUR
T1 - Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways
AU - Melanoma GWAS Consortium
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 - Lui, Fan
AU - Wright, Margaret J.
AU - Henders, Anjali K.
AU - Bowdler, Lisa
AU - Glass, Dan
AU - Ikram, Arfan M.
AU - Uitterlinden, André G.
AU - Madden, Pamela A.
AU - Heath, Andrew C.
AU - Nelson, Elliot 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 - 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.
N1 - Funding Information:
18Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 19Institut National de la Santé et de la Recherche Médicale (INSERM), UMR-946, Genetic Variation and Human Diseases Unit, Paris, France. 20Centre for Genetic Origins of Health and Disease, Faculty of Medicine, Dentistry and Health Sciences, The University of Western Australia, Western Australia, Australia. 21Departments of Epidemiology and Biostatistics, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, P. R. China. 22Division of Molecular Genetic Epidemiology, German Cancer Research Center, Im Neuenheimer Feld 580, Heidelberg, Germany. 23Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. 24Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK. 25Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK. 26Department of Dermatology, University of Athens School of Medicine, Andreas Sygros Hospital, Athens, Greece. 27Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK. 28Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, University of Bergen, Bergen, Norway. 29Department of Pathology, Molecular Pathology, Oslo University Hospital, Rikshospitalet, Oslo, Norway. 30Assistance Publique–Hôpitaux de Paris, Hôpital Cochin, Service de Dermatologie, Université Paris Descartes, Paris, France. 31Department of Dermatology, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv, Israel. 32Department of Internal Medicine and Medical Specialities, University of Genoa, Genoa, Italy. 33Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Publisher Copyright:
© 2018, The Author(s).
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.
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 - 30429480
AN - SCOPUS:85047573234
SN - 2041-1723
VL - 9
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 4774
ER -