A unique genome-wide association analysis in extended Utah high-risk pedigrees identifies a novel melanoma risk variant on chromosome arm 10q

Hum Genet. 2012 Jan;131(1):77-85. doi: 10.1007/s00439-011-1048-z. Epub 2011 Jun 26.


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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Case-Control Studies
  • Chromosomes, Human, Pair 10 / genetics*
  • Female
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study*
  • Genotype
  • Humans
  • Linkage Disequilibrium
  • Male
  • Melanoma / genetics*
  • Pedigree
  • Polymorphism, Single Nucleotide / genetics*
  • Risk Factors
  • Utah