TY - JOUR
T1 - A unique genome-wide association analysis in extended Utah high-risk pedigrees identifies a novel melanoma risk variant on chromosome arm 10q
AU - Teerlink, Craig
AU - Farnham, James
AU - Allen-Brady, Kristina
AU - Camp, Nicola J.
AU - Thomas, Alun
AU - Leachman, Sancy
AU - Cannon-Albright, Lisa
N1 - Funding Information:
Acknowledgments L.A. C-A acknowledges support from the Huntsman Cancer Foundation. NIH National Cancer Institute grant R01 CA102422 (to L.A. C-A). Research was supported by the Utah Cancer Registry, which is funded by contract N01-PC-35141 from the National Cancer Institute’s SEER program with additional support from the Utah State Department of Health and the University of Utah. Partial support for all data sets with in the Utah Population Database (UPDB) was provided by Huntsman Cancer Institute, University of Utah and the Huntsman Cancer Institute’s Cancer Center Support grant, P30 CA42014 from National Cancer Institute. Some research support provided by the University of Utah General Clinical Research Center, PHS grant number UL1-RR025764.
PY - 2012/1
Y1 - 2012/1
N2 - 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.
AB - 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.
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U2 - 10.1007/s00439-011-1048-z
DO - 10.1007/s00439-011-1048-z
M3 - Article
C2 - 21706340
AN - SCOPUS:84856641278
SN - 0340-6717
VL - 131
SP - 77
EP - 85
JO - Human genetics
JF - Human genetics
IS - 1
ER -