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

• 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. © 2018, The Author(s).

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)

Nyckelord

cytochrome P450 1B1

histone deacetylase 4

interferon regulatory factor 4

peroxisome proliferator activated receptor gamma coactivator 1beta

actin binding protein

carrier protein

CYP1B1 protein, human

DOCK8 protein, human

G protein coupled receptor

GPRC5A protein, human

guanine nucleotide exchange factor

HDAC4 protein, human

histone deacetylase

interferon regulatory factor

interferon regulatory factor-4

KITLG protein, human

microRNA

MIRN146 microRNA, human

nerve protein

nuclear protein

phospholipase A2 group VI

PLA2G6 protein, human

PPARGC1B protein, human

repressor protein

RNA

stem cell factor

Stn1 protein, human

SYNE2 protein, human

telomerase

telomerase RNA

telomere binding protein

biology

cancer

gene

gene expression

meta-analysis

risk assessment

skin

Article

Australia

cutaneous melanoma

gene locus

genetic risk

genome-wide association study

human

meta analysis (topic)

Netherlands

pigmented nevus

single nucleotide polymorphism

telomere homeostasis

United Kingdom

United States

Caucasian

genetic predisposition

genetics

melanoma

meta analysis

pleiotropy

skin tumor

Carrier Proteins

Cytochrome P-450 CYP1B1

European Continental Ancestry Group

Genetic Pleiotropy

Genetic Predisposition to Disease

Genome-Wide Association Study

Group VI Phospholipases A2

Guanine Nucleotide Exchange Factors

Histone Deacetylases

Humans

Interferon Regulatory Factors

Melanoma

Microfilament Proteins

MicroRNAs

Nerve Tissue Proteins

Nevus, Pigmented

Nuclear Proteins

Polymorphism, Single Nucleotide

Receptors, G-Protein-Coupled

Repressor Proteins

Skin Neoplasms

Stem Cell Factor

Telomerase

Telomere-Binding Proteins

Publikations- och innehållstyp

art (ämneskategori)

ref (ämneskategori)