In:
Gut, BMJ, Vol. 67, No. 3 ( 2018-03), p. 521-533
Abstract:
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 tumour-derived tissue samples (n=115) from The Cancer Genome Atlas were 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 tumour-derived tissues (false discovery rate 〈 0.1), with the strongest effects seen near transcriptional start sites. Approximately 23% and 42% of genes with significant cis -eQTLs appeared to be specific for tumour-derived and normal-derived tissues, respectively. Significant enrichment of cis -eQTL variants was noted in non-coding regulatory regions, in particular for pancreatic tissues (1.53-fold to 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=5.8×10 −8 ) and tumour-derived (p=8.3×10 −5 ) tissues. The high linkage disequilibrium 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 data set for further studies on gene expression and its regulation in pancreatic tissues.
Type of Medium:
Online Resource
ISSN:
0017-5749
,
1468-3288
DOI:
10.1136/gutjnl-2016-313146
DOI:
10.1136/gutjnl-2016-313146.supp1
DOI:
10.1136/gutjnl-2016-313146.supp4
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10.1136/gutjnl-2016-313146.supp5
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10.1136/gutjnl-2016-313146.supp2
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10.1136/gutjnl-2016-313146.supp3
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10.1136/gutjnl-2016-313146.supp6
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10.1136/gutjnl-2016-313146.supp7
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10.1136/gutjnl-2016-313146.supp8
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10.1136/gutjnl-2016-313146.supp9
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10.1136/gutjnl-2016-313146.supp10
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10.1136/gutjnl-2016-313146.supp13
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10.1136/gutjnl-2016-313146.supp11
DOI:
10.1136/gutjnl-2016-313146.supp12
DOI:
10.1136/gutjnl-2016-313146.supp14
DOI:
10.1136/gutjnl-2016-313146.supp15
DOI:
10.1136/gutjnl-2016-313146.supp16
DOI:
10.1136/gutjnl-2016-313146.supp17
DOI:
10.1136/gutjnl-2016-313146.supp18
DOI:
10.1136/gutjnl-2016-313146.supp19
DOI:
10.1136/gutjnl-2016-313146.supp20
Language:
English
Publisher:
BMJ
Publication Date:
2018
detail.hit.zdb_id:
1492637-4
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