Journal article
Characterizing cis-regulatory variation in the transcriptome of histologically normal and tumor-derived pancreatic tissues
- Abstract:
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Objective
To elucidate the genetic architecture of gene expression in pancreatic tissues.
Design
We performed expression quantitative trait locus (eQTL) analysis in histologically normal pancreatic tissue samples (n=95) using RNA-sequencing and the corresponding 1000 Genomes imputed germline genotypes. Data from pancreatic tumor-derived tissue samples (n=115) from The Cancer Genome Atlas (TCGA) was included for comparison.
Results
We identified 38,615 cis-eQTLs (in 484 genes) in histologically normal tissues and 39,713 cis-eQTL (in 237 genes) in tumor-derived tissues (FDR<0.1), with the strongest effects seen near transcriptional start sites (TSS). Approximately 23% and 42% of genes with significant cis-eQTLs appeared to be specific for tumor and normal derived tissues, respectively. Significant enrichment of cis-eQTL variants was noted in noncoding regulatory regions, in particular for pancreatic tissues (1.53-3.12 fold, P≤0.0001), indicating tissue-specific functional relevance. A common pancreatic cancer risk locus on 9q34.2 (rs687289) was associated with ABO expression in histologically normal (P=5.8x10-8) and tumor-derived (P=8.3x10-5) tissues. The high linkage disequilibrium (LD) between this variant and the O blood group generating deletion variant in ABO (exon 6) suggested that nonsense-mediated decay (NMD) of the “O” mRNA might explain this finding. However, knockdown of crucial NMD regulators did not influence decay of the ABO “O” mRNA, indicating that a gene regulatory element influenced by pancreatic cancer risk alleles may underlie the eQTL.
Conclusions
We have identified cis-eQTLs representing potential functional regulatory variants in the pancreas and generated a rich dataset for further studies on gene expression and its regulation in pancreatic tissues.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
Actions
Access Document
- Files:
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(Preview, Accepted manuscript, pdf, 419.2KB, Terms of use)
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- Publisher copy:
- 10.1136/gutjnl-2016-313146
Authors
- Funding agency for:
- McCarthy, M
- Grant:
- U01-DK105535
- Publisher:
- BMJ Publishing Group
- Journal:
- Gut More from this journal
- Volume:
- 67
- Pages:
- 521-533
- Publication date:
- 2017-06-20
- Acceptance date:
- 2017-04-11
- DOI:
- EISSN:
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1468-3288
- ISSN:
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0017-5749
- Pubs id:
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pubs:697024
- UUID:
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uuid:90a82ed4-8ee7-4bef-b678-5797970b4a02
- Local pid:
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pubs:697024
- Source identifiers:
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697024
- Deposit date:
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2017-05-24
- ARK identifier:
Terms of use
- Copyright holder:
- McCarthy et al
- Copyright date:
- 2017
- Notes:
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© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
This is the accepted manuscript version of the article. The final version is available online from the BMJ Publishing Group at: http://dx.doi.org/10.1136/gutjnl-2016-313146
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