title: A unique genome-wide association analysis in extended Utah high-risk pedigrees identifies a novel melanoma risk variant on chromosome arm 10q.
abstract: Only two genome-wide association (GWA) screens have been published for melanoma (Nat Genet 47:920-925, 2009; Nat Genet 40:838-840, 2008). Using a unique approach, we performed a genome-wide association study in 156 related melanoma cases from 34 high-risk Utah pedigrees. Genome-wide association analysis was performed on nearly 500,000 markers; we compared cases to 2,150 genotypically matched samples from Illumina's iControls database. We performed genome-wide association with EMMAX software, which is designed to account for population structure, including relatedness between cases. Three SNPs exceeded a genome-wide significance threshold of p < 5 × 10(-8) on chromosome arm 10q25.1 (rs17119434, rs17119461, and rs17119490), where the most extreme p value was 7.21 × 10(-12). This study represents a new and unique approach to predisposition gene identification; and it is the first genome-wide association study performed in related cases in high-risk pedigrees. Our approach illustrates an example of using high-risk pedigrees for the identification of new melanoma predisposition variants.
authors.affiliation: Division of Genetic Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT 84132, USA. craig.teerlink@utah.edu
authors.forename: Craig
authors.initials: C
authors.lastname: Teerlink
authors.forename: James
authors.initials: J
authors.lastname: Farnham
authors.forename: Kristina
authors.initials: K
authors.lastname: Allen-Brady
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Camp
authors.forename: Alun
authors.initials: A
authors.lastname: Thomas
authors.forename: Sancy
authors.initials: S
authors.lastname: Leachman
authors.forename: Lisa
authors.initials: L
authors.lastname: Cannon-Albright
mesh_terms: D016022:Case-Control Studies; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008545:Melanoma / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D014589:Utah