Original Investigation

Human Genetics

, Volume 131, Issue 1, pp 77-85

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

  • Craig TeerlinkAffiliated withDivision of Genetic Epidemiology, Department of Internal Medicine, University of Utah School of Medicine Email author 
  • , James FarnhamAffiliated withDivision of Genetic Epidemiology, Department of Internal Medicine, University of Utah School of Medicine
  • , Kristina Allen-BradyAffiliated withDivision of Genetic Epidemiology, Department of Internal Medicine, University of Utah School of Medicine
  • , Nicola J. CampAffiliated withDivision of Genetic Epidemiology, Department of Internal Medicine, University of Utah School of Medicine
  • , Alun ThomasAffiliated withDivision of Genetic Epidemiology, Department of Internal Medicine, University of Utah School of Medicine
  • , Sancy LeachmanAffiliated withDepartment of Dermatology, University of Utah School of Medicine
  • , Lisa Cannon-AlbrightAffiliated withDivision of Genetic Epidemiology, Department of Internal Medicine, University of Utah School of MedicineGeorge E. Wahlen Department of Veterans Affairs Medical Center

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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.