Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways

Melanoma GWAS Consortium

doi:10.1038/s41467-018-06649-5

Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways

Melanoma GWAS Consortium

Indiana University-Purdue University Indianapolis
St Thomas' Hospital
University of Leeds
Sophia Children's Hospital
Medical Research Council (MRC)
University of Bristol
Translational Research Institute
University of Queensland
University of Western Australia
Harvard School of Public Health
UMIST
University of Texas MD Anderson Cancer Center
INSERM, U968
Tianjin Medical University
DKFZ (Deutsches Krebsforschungszentrum Heidelberg)
University of Cambridge
The Institute of Cancer Research (University of London)
Athens University Medical School
University of Bergen
Oslo University Hospital
ASSISTANCE PUBLIQUE HOPITAUX DE PARIS
Chaim Sheba Medical Center
Università di Genova
National Cancer Institute
Pomeranian Medical University
University of Pennsylvania
QIMR Berghofer Medical Research Institute

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	4774
Journal	Nature Communications
Volume	9
Issue number	1
Early online date	14 Nov 2018
DOIs	https://doi.org/10.1038/s41467-018-06649-5
Publication status	Published - 2018

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SDG 3 Good Health and Well-being

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@article{2c12987871724f7c993fa347c187bb45,

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.",

author = "\{Melanoma GWAS Consortium\} and Duffy, \{David L.\} and Gu Zhu and Xin Li and Marianna Sanna and Iles, \{Mark M.\} and Jacobs, \{Leonie C.\} and Evans, \{David M.\} and Seyhan Yazar and Jonathan Beesley and Law, \{Matthew H.\} and Peter Kraft and Alessia Visconti and Taylor, \{John C.\} and Fan Lui and Wright, \{Margaret J.\} and Henders, \{Anjali K.\} and Lisa Bowdler and Dan Glass and Ikram, \{Arfan M.\} and Uitterlinden, \{Andr{\'e} G.\} and Madden, \{Pamela A.\} and Heath, \{Andrew C.\} and Nelson, \{Elliot C.\} and Green, \{Adele C.\} and Stephen Chanock and Barrett, \{Jennifer H.\} and Brown, \{Matthew A.\} and Hayward, \{Nicholas K.\} and Stuart MacGregor and Sturm, \{Richard A.\} and Hewitt, \{Alex W.\} and Lee, \{Jeffrey E.\} and Myriam Brossard and Moses, \{Eric K.\} and Fengju Song and Rajiv Kumar and Easton, \{Douglas F.\} and Pharoah, \{Paul D.P.\} and Swerdlow, \{Anthony J.\} and Kypreou, \{Katerina P.\} and Mark Harland and Juliette Randerson-Moor and Akslen, \{Lars A.\} and Andresen, \{Per A.\} and Avril, \{Marie Fran{\c c}oise\} and Esther Azizi and Scarr{\`a}, \{Giovanna Bianchi\} and Brown, \{Kevin M.\} and Tadeusz D{\c e}bniak and Elder, \{David E.\}",

year = "2018",

doi = "10.1038/s41467-018-06649-5",

language = "English",

volume = "9",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

}

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.

PY - 2018

Y1 - 2018

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 - https://www.scopus.com/pages/publications/85047573234

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 -

Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways

Abstract

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