Scientific Publications by FDA Staff

Gut 2018 Mar;67(3):521-33

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

Zhang M, Lykke-Andersen S, Zhu B, Xiao W, Hoskins JW, Zhang X, Rost LM, Collins I, Bunt MV, Jia J, Parikh H, Zhang T, Song L, Jermusyk A, Chung CC, Zhu B, Zhou W, Matters GL, Kurtz RC, Yeager M, Jensen TH, Brown KM, Ongen H, Bamlet WR, Murray BA, McCarthy MI, Chanock SJ, Chatterjee N, Wolpin BM, Smith JP, Olson SH, Petersen GM, Shi J, Amundadottir L

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