Dataset Information

Characterising cis-regulatory variation in the transcriptome of histologically normal and tumour-derived pancreatic tissues.

ABSTRACT: 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 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.

SUBMITTER: Zhang M

PROVIDER: S-EPMC5762429 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Characterising <i>cis</i>-regulatory variation in the transcriptome of histologically normal and tumour-derived pancreatic tissues.

Zhang Mingfeng M Lykke-Andersen Soren S Zhu Bin B Xiao Wenming W Hoskins Jason W JW Zhang Xijun X Rost Lauren M LM Collins Irene I Bunt Martijn van de MV Jia Jinping J Parikh Hemang H Zhang Tongwu T Song Lei L Jermusyk Ashley A Chung Charles C CC Zhu Bin B Zhou Weiyin W Matters Gail L GL Kurtz Robert C RC Yeager Meredith M Jensen Torben Heick TH Brown Kevin M KM Ongen Halit H Bamlet William R WR Murray Bradley A BA McCarthy Mark I MI Chanock Stephen J SJ Chatterjee Nilanjan N Wolpin Brian M BM Smith Jill P JP Olson Sara H SH Petersen Gloria M GM Shi Jianxin J Amundadottir Laufey L

Gut 20170620 3

<h4>Objective</h4>To elucidate the genetic architecture of gene expression in pancreatic tissues.<h4>Design</h4>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.<h4>Results</h4>We identified 38 615 <i>cis</i>-eQTLs (in 484 ge ...[more]

PMID: 28634199

Similar Datasets

Project description:The genetic basis of gene expression variation has long been studied with the aim to understand the landscape of regulatory variants, but also more recently to assist in the interpretation and elucidation of disease signals. To date, many studies have looked in specific tissues and population-based samples, but there has been limited assessment of the degree of inter-population variability in regulatory variation. We analyzed genome-wide gene expression in lymphoblastoid cell lines from a total of 726 individuals from 8 global populations from the HapMap3 project and correlated gene expression levels with HapMap3 SNPs located in cis to the genes. We describe the influence of ancestry on gene expression levels within and between these diverse human populations and uncover a non-negligible impact on global patterns of gene expression. We further dissect the specific functional pathways differentiated between populations. We also identify 5,691 expression quantitative trait loci (eQTLs) after controlling for both non-genetic factors and population admixture and observe that half of the cis-eQTLs are replicated in one or more of the populations. We highlight patterns of eQTL-sharing between populations, which are partially determined by population genetic relatedness, and discover significant sharing of eQTL effects between Asians, European-admixed, and African subpopulations. Specifically, we observe that both the effect size and the direction of effect for eQTLs are highly conserved across populations. We observe an increasing proximity of eQTLs toward the transcription start site as sharing of eQTLs among populations increases, highlighting that variants close to TSS have stronger effects and therefore are more likely to be detected across a wider panel of populations. Together these results offer a unique picture and resource of the degree of differentiation among human populations in functional regulatory variation and provide an estimate for the transferability of complex trait variants across populations.

Dataset Information

Characterising cis-regulatory variation in the transcriptome of histologically normal and tumour-derived pancreatic tissues.

Publications

Characterising <i>cis</i>-regulatory variation in the transcriptome of histologically normal and tumour-derived pancreatic tissues.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets