4.8 Article

Identification of candidate genes for prostate cancer-risk SNPs utilizing a normal prostate tissue eQTL data set

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NATURE COMMUNICATIONS
卷 6, 期 -, 页码 -

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NATURE PORTFOLIO
DOI: 10.1038/ncomms9653

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  1. DOD [W81XWH-11-1-0261]
  2. US Public Health Service, National Institutes of Health [CA151254, CA157881, CA015083]

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Multiple studies have identified loci associated with the risk of developing prostate cancer but the associated genes are not well studied. Here we create a normal prostate tissue-specific eQTL data set and apply this data set to previously identified prostate cancer (PrCa)-risk SNPs in an effort to identify candidate target genes. The eQTL data set is constructed by the genotyping and RNA sequencing of 471 samples. We focus on 146 PrCa-risk SNPs, including all SNPs in linkage disequilibrium with each risk SNP, resulting in 100 unique risk intervals. We analyse cis-acting associations where the transcript is located within 2Mb (+/- 1 Mb) of the risk SNP interval. Of all SNP-gene combinations tested, 41.7% of SNPs demonstrate a significant eQTL signal after adjustment for sample histology and 14 expression principal component covariates. Of the 100 PrCa-risk intervals, 51 have a significant eQTL signal and these are associated with 88 genes. This study provides a rich resource to study biological mechanisms underlying genetic risk to PrCa.

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