title: Genome-wide association study identifies nidogen 1 (NID1) as a susceptibility locus to cutaneous nevi and melanoma risk.
abstract: We conducted a genome-wide association study on the number of melanocytic nevi reported by 9136 individuals of European ancestry, with follow-up replication in 3581 individuals. We identified the nidogen 1 (NID1) gene on 1q42 associated with nevus count (two linked single nucleotide polymorphisms with r(2) > 0.9: rs3768080 A allele associated with reduced count, P = 6.5 × 10(-8); and rs10754833 T allele associated with reduced count, P = 1.5 × 10(-7)). We further determined that the rs10754833 [T] was associated with a decreased melanoma risk in 2368 melanoma cases and 7432 controls [for CT genotype: odds ratio (OR) = 0.86, 95% confidence interval (CI) = 0.75-0.99, P = 0.04; for TT genotype: OR = 0.84, 95% CI = 0.71-0.98, P = 0.03]. Expression level of the NID1 locus was 2-fold higher for the rs10754833 T allele carriers than that with the CC genotype (P = 0.017) in the 87 HapMap CEU cell lines. The NID1 gene is a biologically plausible locus for nevogenesis and melanoma development, with decreased expression levels of NID1 in benign nevi (P = 3.5 × 10(-6)) and in primary melanoma (P = 4.6 × 10(-4)) compared with the normal skin.
authors.affiliation: Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Nan
authors.forename: Mousheng
authors.initials: M
authors.lastname: Xu
authors.forename: Jiangwen
authors.initials: J
authors.lastname: Zhang
authors.forename: Mingfeng
authors.initials: M
authors.lastname: Zhang
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.forename: Abrar A
authors.initials: AA
authors.lastname: Qureshi
authors.forename: Constance
authors.initials: C
authors.lastname: Chen
authors.forename: Qun
authors.initials: Q
authors.lastname: Guo
authors.forename: Frank B
authors.initials: FB
authors.lastname: Hu
authors.forename: Eric B
authors.initials: EB
authors.lastname: Rimm
authors.forename: Gary
authors.initials: G
authors.lastname: Curhan
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Song
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Amos
authors.forename: Li-E
authors.initials: LE
authors.lastname: Wang
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Lee
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
authors.forename: David J
authors.initials: DJ
authors.lastname: Hunter
authors.forename: Jiali
authors.initials: J
authors.lastname: Han
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D009508:Nevus, Pigmented / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012306:Risk; D012878:Skin Neoplasms / Q000235:genetics*
chemical_list: D008562:Membrane Glycoproteins; C029967:nidogen