title: Identification of candidate genes for prostate cancer-risk SNPs utilizing a normal prostate tissue eQTL data set.
abstract: 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 2 Mb (±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.
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, Minnesota 55905, USA.
authors.forename: S N
authors.initials: SN
authors.lastname: Thibodeau
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, Minnesota 55905, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: French
authors.affiliation: Department of Health Sciences Research, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, Minnesota 55905, USA.
authors.forename: S K
authors.initials: SK
authors.lastname: McDonnell
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, Minnesota 55905, USA.
authors.forename: J
authors.initials: J
authors.lastname: Cheville
authors.affiliation: Department of Health Sciences Research, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, Minnesota 55905, USA.
authors.forename: S
authors.identifier: http://orcid.org/0000-0003-4135-6268
authors.initials: S
authors.lastname: Middha
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, Minnesota 55905, USA.
authors.forename: L
authors.initials: L
authors.lastname: Tillmans
authors.affiliation: Department of Health Sciences Research, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, Minnesota 55905, USA.
authors.forename: S
authors.initials: S
authors.lastname: Riska
authors.affiliation: Department of Health Sciences Research, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, Minnesota 55905, USA.
authors.forename: S
authors.initials: S
authors.lastname: Baheti
authors.affiliation: Department of Health Sciences Research, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, Minnesota 55905, USA.
authors.forename: M C
authors.initials: MC
authors.lastname: Larson
authors.affiliation: Department of Health Sciences Research, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, Minnesota 55905, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Fogarty
authors.affiliation: Department of Epidemiology and Public Health, University of Maryland School of Medicine, 660W Redwood Street, Baltimore, Maryland 21201, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Health Sciences Research, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, Minnesota 55905, USA.
authors.forename: N
authors.initials: N
authors.lastname: Larson
authors.affiliation: Department of Health Sciences Research, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, Minnesota 55905, USA.
authors.forename: A
authors.initials: A
authors.lastname: Nair
authors.affiliation: Department of Health Sciences Research, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, Minnesota 55905, USA.
authors.forename: D
authors.initials: D
authors.lastname: O'Brien
authors.affiliation: Department of Pathology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, Wisconsin 53226, USA.
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Health Sciences Research, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, Minnesota 55905, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Schaid
mesh_terms: D030541:Databases, Genetic; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics*; D040641:Quantitative Trait Loci; D050436:Regulatory Elements, Transcriptional; D017423:Sequence Analysis, RNA