Variants at IRX4 as prostate cancer expression quantitative trait loci Journal Article


Authors: Xu, X.; Hussain, W. M.; Vijai, J.; Offit, K.; Rubin, M. A.; Demichelis, F.; Klein, R. J.
Article Title: Variants at IRX4 as prostate cancer expression quantitative trait loci
Abstract: Genome-wide association studies (GWAS) have identified numerous prostate cancer-associated risk loci. Some variants at these loci may be regulatory and influence expression of nearby genes. Such loci are known as cis-expression quantitative trait loci (cis-eQTL). As cis-eQTLs are highly tissue-specific, we asked if GWAS-identified prostate cancer risk loci are cis-eQTLs in human prostate tumor tissues. We investigated 50 prostate cancer samples for their genotype at 59 prostate cancer risk-associated single-nucleotide polymorphisms (SNPs) and performed cis-eQTL analysis of transcripts from paired primary tumors within two megabase windows. We tested 586 transcript-genotype associations, of which 27 were significant (false discovery rate ≤10%). An equivalent eQTL analysis of the same prostate cancer risk loci in lymphoblastoid cell lines did not result in any significant associations. The top-ranked cis-eQTL involved the IRX4 (Iroquois homeobox protein 4) transcript and rs12653946, tagged by rs10866528 in our study (P=4.91 × 10 -5). Replication studies, linkage disequilibrium, and imputation analyses highlight population specificity at this locus. We independently validated IRX4 as a potential prostate cancer risk gene through cis-eQTL analysis of prostate cancer risk variants. Cis-eQTL analysis in relevant tissues, even with a small sample size, can be a powerful method to expedite functional follow-up of GWAS. © 2014 Macmillan Publishers Limited.
Keywords: clinical article; human tissue; human cell; single nucleotide polymorphism; follow up; gene expression; genetic association; genetic variability; genotype; prostate cancer; oncogene; genetic risk; quantitative trait locus; lymphoblastoid cell line; tissue specificity; gene linkage disequilibrium; gwas; human; male; priority journal; article; eqtl; expression quantitative trait loci; irx4; risk snps; irx4 gene
Journal Title: European Journal of Human Genetics
Volume: 22
Issue: 4
ISSN: 1018-4813
Publisher: Nature Publishing Group  
Date Published: 2014-04-01
Start Page: 558
End Page: 563
Language: English
DOI: 10.1038/ejhg.2013.195
PROVIDER: scopus
PMCID: PMC3953920
PUBMED: 24022300
DOI/URL:
Notes: Export Date: 1 May 2014 -- CODEN: EJHGE -- Source: Scopus
Altmetric Score
MSK Authors
  1. Kenneth Offit
    538 Offit
  2. Robert J. Klein
    60 Klein
  3. Vijai Joseph
    126 Joseph
  4. Xing Xu
    5 Xu