Genome-wide association study identifies variants at 9p21 and 22q13 associated with development of cutaneous nevi.
A high melanocytic nevi count is the strongest known risk factor for cutaneous melanoma. We conducted a genome-wide association study for nevus count using 297,108 SNPs in 1,524 twins, with validation in an independent cohort of 4,107 individuals. We identified strongly associated variants in MTAP, a gene adjacent to the familial melanoma susceptibility locus CDKN2A on 9p21 (rs4636294, combined P = 3.4 x 10(-15)), as well as in PLA2G6 on 22q13.1 (rs2284063, combined P = 3.4 x 10(-8)). In addition, variants in these two loci showed association with melanoma risk in 3,131 melanoma cases from two independent studies, including rs10757257 at 9p21, combined P = 3.4 x 10(-8), OR = 1.23 (95% CI = 1.15-1.30) and rs132985 at 22q13.1, combined P = 2.6 x 10(-7), OR = 1.23 (95% CI = 1.15-1.30). This provides the first report of common variants associated to nevus number and demonstrates association of these variants with melanoma susceptibility.
Falchi
Mario
M
Department of Twin Research & Genetic Epidemiology, Kings College London, St. Thomas' Hospital Campus, London, UK. m.falchi@imperial.ac.uk
Bataille
Veronique
V
Hayward
Nicholas K
NK
Duffy
David L
DL
Bishop
Julia A Newton
JA
Pastinen
Tomi
T
Cervino
Alessandra
A
Zhao
Zhen Z
ZZ
Deloukas
Panos
P
Soranzo
Nicole
N
Elder
David E
DE
Barrett
Jennifer H
JH
Martin
Nicholas G
NG
Bishop
D Timothy
DT
Montgomery
Grant W
GW
Spector
Timothy D
TD
D000483:Alleles; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006720:Homozygote; D006801:Humans; D008545:Melanoma / Q000235:genetics; D009506:Nevus / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011230:Precancerous Conditions / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics*; D006113:United Kingdom