title: Fine mapping of genetic susceptibility loci for melanoma reveals a mixture of single variant and multiple variant regions.
abstract: At least 17 genomic regions are established as harboring melanoma susceptibility variants, in most instances with genome-wide levels of significance and replication in independent samples. Based on genome-wide single nucleotide polymorphism (SNP) data augmented by imputation to the 1,000 Genomes reference panel, we have fine mapped these regions in over 5,000 individuals with melanoma (mainly from the GenoMEL consortium) and over 7,000 ethnically matched controls. A penalized regression approach was used to discover those SNP markers that most parsimoniously explain the observed association in each genomic region. For the majority of the regions, the signal is best explained by a single SNP, which sometimes, as in the tyrosinase region, is a known functional variant. However in five regions the explanation is more complex. At the CDKN2A locus, for example, there is strong evidence that not only multiple SNPs but also multiple genes are involved. Our results illustrate the variability in the biology underlying genome-wide susceptibility loci and make steps toward accounting for some of the "missing heritability."
authors: Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, United Kingdom.
authors: Jennifer H
authors: JH
authors: Barrett
authors: John C
authors: JC
authors: Taylor
authors: Chloe
authors: C
authors: Bright
authors: Mark
authors: M
authors: Harland
authors: Alison M
authors: AM
authors: Dunning
authors: Lars A
authors: LA
authors: Akslen
authors: Per A
authors: PA
authors: Andresen
authors: Marie-Françoise
authors: MF
authors: Avril
authors: Esther
authors: E
authors: Azizi
authors: Giovanna
authors: G
authors: Bianchi Scarrà
authors: Myriam
authors: M
authors: Brossard
authors: Kevin M
authors: KM
authors: Brown
authors: Tadeusz
authors: T
authors: Dębniak
authors: David E
authors: DE
authors: Elder
authors: Eitan
authors: E
authors: Friedman
authors: Paola
authors: P
authors: Ghiorzo
authors: Elizabeth M
authors: EM
authors: Gillanders
authors: Nelleke A
authors: NA
authors: Gruis
authors: Johan
authors: J
authors: Hansson
authors: Per
authors: P
authors: Helsing
authors: Marko
authors: M
authors: Hočevar
authors: Veronica
authors: V
authors: Höiom
authors: Christian
authors: C
authors: Ingvar
authors: Maria Teresa
authors: MT
authors: Landi
authors: Julie
authors: J
authors: Lang
authors: G Mark
authors: GM
authors: Lathrop
authors: Jan
authors: J
authors: Lubiński
authors: Rona M
authors: RM
authors: Mackie
authors: Anders
authors: A
authors: Molven
authors: Srdjan
authors: S
authors: Novaković
authors: Håkan
authors: H
authors: Olsson
authors: Susana
authors: S
authors: Puig
authors: Joan Anton
authors: JA
authors: Puig-Butille
authors: Nienke
authors: N
authors: van der Stoep
authors: Remco
authors: R
authors: van Doorn
authors: Wilbert
authors: W
authors: van Workum
authors: Alisa M
authors: AM
authors: Goldstein
authors: Peter A
authors: PA
authors: Kanetsky
authors: Paul D P
authors: PD
authors: Pharoah
authors: Florence
authors: F
authors: Demenais
authors: Nicholas K
authors: NK
authors: Hayward
authors: Julia A
authors: JA
authors: Newton Bishop
authors: D Timothy
authors: DT
authors: Bishop
authors: Mark M
authors: MM
authors: Iles
mesh_terms: D002874:Chromosome Mapping; D019938:Cyclin D1 / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D006801:Humans; D008545:Melanoma / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D019098:Telomerase / Q000235:genetics
chemical_list: C530104:CCND1 protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019938:Cyclin D1; C509186:TERT protein, human; D019098:Telomerase
keywords: fine mapping; genome-wide signal; heritability; melanoma; penalized regression