Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
QIMR Home Page
GenEpi Home Page
About GenEpi
Publications
Contacts
Research
Staff Index
Collaborators
Software Tools
Computing Resources
Studies
Search
GenEpi Intranet
PMID
30429480
TITLE
Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways.
ABSTRACT
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.
DATE PUBLISHED
2018 11 14
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2017/08/03
accepted 2018/09/13
entrez 2018/11/16 06:00
pubmed 2018/11/16 06:00
medline 2019/04/16 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Duffy DL Duffy David L DL QIMR Berghofer Medical Research Institute, Brisbane, Australia. David.Duffy@qimrberghofer.edu.au.
Zhu G Zhu Gu G QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Li X Li Xin X Department of Epidemiology, Richard M. Fairbanks School of Public Health, Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, IN, 63110, USA.
Sanna M Sanna Marianna M Department of Twin Research & Genetic Epidemiology, St Thomas Hospital Campus, Kings College, London, UK.
Iles MM Iles Mark M MM Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
Jacobs LC Jacobs Leonie C LC Department of Dermatology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands.
Evans DM Evans David M DM University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia.
Yazar S Yazar Seyhan S Centre for Ophthalmology and Vision Science, University of Western Australia and the Lions Eye Institute, Perth, Australia.
Beesley J Beesley Jonathan J QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Law MH Law Matthew H MH QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Kraft P Kraft Peter P Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, 02115, MA, USA.
Visconti A Visconti Alessia A Department of Twin Research & Genetic Epidemiology, St Thomas Hospital Campus, Kings College, London, UK.
Taylor JC Taylor John C JC Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
Liu F Liu Fan F Department of Genetic Identification, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands.
Wright MJ Wright Margaret J MJ QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Henders AK Henders Anjali K AK Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
Bowdler L Bowdler Lisa L QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Glass D Glass Dan D Department of Twin Research & Genetic Epidemiology, St Thomas Hospital Campus, Kings College, London, UK.
Ikram MA Ikram M Arfan MA Department of Epidemiology, Erasmus MC, Rotterdam, Netherlands.
Uitterlinden AG Uitterlinden André G AG Department of Internal Medicine, Erasmus MC, Rotterdam, Netherlands.
Madden PA Madden Pamela A PA Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Heath AC Heath Andrew C AC Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Nelson EC Nelson Elliot C EC Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Green AC Green Adele C AC Molecular Oncology Group, CRUK Manchester Institute, University of Manchester, Manchester, UK.
Chanock S Chanock Stephen S Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Barrett JH Barrett Jennifer H JH Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
Brown MA Brown Matthew A MA University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia.
Hayward NK Hayward Nicholas K NK QIMR Berghofer Medical Research Institute, Brisbane, Australia.
MacGregor S MacGregor Stuart S QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Sturm RA Sturm Richard A RA Dermatology Research Centre, University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia.
Hewitt AW Hewitt Alex W AW Centre for Ophthalmology and Vision Science, University of Western Australia and the Lions Eye Institute, Perth, Australia.
Melanoma GWAS Consortium
Kayser M Kayser Manfred M Department of Genetic Identification, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands.
Hunter DJ Hunter David J DJ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, 02115, MA, USA.
Newton Bishop JA Newton Bishop Julia A JA Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
Spector TD Spector Timothy D TD Department of Twin Research & Genetic Epidemiology, St Thomas Hospital Campus, Kings College, London, UK.
Montgomery GW Montgomery Grant W GW Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
Mackey DA Mackey David A DA Centre for Ophthalmology and Vision Science, University of Western Australia and the Lions Eye Institute, Perth, Australia.
Smith GD Smith George Davey GD MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Nijsten TE Nijsten Tamar E TE Department of Dermatology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands.
Bishop DT Bishop D Timothy DT Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
Bataille V Bataille Veronique V Department of Twin Research & Genetic Epidemiology, St Thomas Hospital Campus, Kings College, London, UK.
Falchi M Falchi Mario M Department of Twin Research & Genetic Epidemiology, St Thomas Hospital Campus, Kings College, London, UK.
Han J Han Jiali J Department of Epidemiology, Richard M. Fairbanks School of Public Health, Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, IN, 63110, USA.
Martin NG Martin Nicholas G NG QIMR Berghofer Medical Research Institute, Brisbane, Australia.
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
Lee Jeffrey E JE
Brossard Myriam M
Moses Eric K EK
Song Fengju F
Kumar Rajiv R
Easton Douglas F DF
Pharoah Paul D P PDP
Swerdlow Anthony J AJ
Kypreou Katerina P KP
Harland Mark M
Randerson-Moor Juliette J
Akslen Lars A LA
Andresen Per A PA
Avril Marie-Françoise MF
Azizi Esther E
Scarrà Giovanna Bianchi GB
Brown Kevin M KM
Dębniak Tadeusz T
Elder David E DE
Fang Shenying S
Friedman Eitan E
Galan Pilar P
Ghiorzo Paola P
Gillanders Elizabeth M EM
Goldstein Alisa M AM
Gruis Nelleke A NA
Hansson Johan J
Helsing Per P
Hočevar Marko M
Höiom Veronica V
Ingvar Christian C
Kanetsky Peter A PA
Chen Wei V WV
Landi Maria Teresa MT
Lang Julie J
Lathrop G Mark GM
Lubiński Jan J
Mackie Rona M RM
Mann Graham J GJ
Molven Anders A
Novaković Srdjan S
Olsson Håkan H
Puig Susana S
Puig-Butille Joan Anton JA
Radford-Smith Graham L GL
van der Stoep Nienke N
van Doorn Remco R
Whiteman David C DC
Craig Jamie E JE
Schadendorf Dirk D
Simms Lisa A LA
Burdon Kathryn P KP
Nyholt Dale R DR
Pooley Karen A KA
Orr Nicholas N
Stratigos Alexander J AJ
Cust Anne E AE
Ward Sarah V SV
Schulze Hans-Joachim HJ
Dunning Alison M AM
Demenais Florence F
Amos Christopher I CI
JOURNAL
VOLUME: 9
ISSUE: 1
TITLE: Nature communications
ISOABBREVIATION: Nat Commun
YEAR: 2018
MONTH: 11
DAY: 14
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 2041-1723
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Nat Commun
COUNTRY: England
ISSNLINKING: 2041-1723
NLMUNIQUEID: 101528555
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Meta-Analysis
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
ErratumIn Nat Commun. 2019 Jan 14;10(1):299 30643134
GRANTS
GRANTID AGENCY COUNTRY
12-0023 Worldwide Cancer Research United Kingdom
MC_UU_00011/1 Medical Research Council United Kingdom
P30 CA008748 NCI NIH HHS United States
MC_UU_12013/4 Medical Research Council United Kingdom
10589 Cancer Research UK United Kingdom
MR/L01629X/1 Medical Research Council United Kingdom
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Carrier Proteins genetics
Cytochrome P-450 CYP1B1 genetics
European Continental Ancestry Group genetics
Genetic Pleiotropy genetics
Genetic Predisposition to Disease genetics
Genome-Wide Association Study genetics
Group VI Phospholipases A2 genetics
Guanine Nucleotide Exchange Factors genetics
Histone Deacetylases genetics
Humans genetics
Interferon Regulatory Factors genetics
Melanoma genetics
MicroRNAs genetics
Microfilament Proteins genetics
Nerve Tissue Proteins genetics
Nevus, Pigmented genetics
Nuclear Proteins genetics
Polymorphism, Single Nucleotide genetics
RNA genetics
RNA-Binding Proteins genetics
Receptors, G-Protein-Coupled genetics
Repressor Proteins genetics
Skin Neoplasms genetics
Stem Cell Factor genetics
Telomerase genetics
Telomere-Binding Proteins genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Carrier Proteins
0 DOCK8 protein, human
0 GPRC5A protein, human
0 Guanine Nucleotide Exchange Factors
0 Interferon Regulatory Factors
0 KITLG protein, human
0 MIRN146 microRNA, human
0 MicroRNAs
0 Microfilament Proteins
0 Nerve Tissue Proteins
0 Nuclear Proteins
0 PPARGC1B protein, human
0 RNA-Binding Proteins
0 Receptors, G-Protein-Coupled
0 Repressor Proteins
0 SYNE2 protein, human
0 Stem Cell Factor
0 Stn1 protein, human
0 Telomere-Binding Proteins
0 interferon regulatory factor-4
0 telomerase RNA
63231-63-0 RNA
EC 1.14.14.1 CYP1B1 protein, human
EC 1.14.14.1 Cytochrome P-450 CYP1B1
EC 2.7.7.49 Telomerase
EC 3.1.1.4 Group VI Phospholipases A2
EC 3.1.1.4 PLA2G6 protein, human
EC 3.5.1.98 HDAC4 protein, human
EC 3.5.1.98 Histone Deacetylases
OTHER ID's